Biological

macromolecules
MLS 218
Objectives
 Identify the major classes of macromolecules
 Differentiate between monomers and polymers
 Describe the important structural features of
carbohydrates, lipids, nucleic acids and proteins.
 Identify functional groups in macromolecules
 Describe synthesis of polymers ( macromolecules)
 Describe the formation of a glycosidic linkage.
 Compare and contrast the structures, functions, and
locations of starch, glycogen, cellulose and chitin.
 Identify an ester linkage and describe how it is formed.
 Distinguish between saturated and unsaturated fats.
 Describe the process that results in the production of
trans fat molecules
 Distinguish between different types of protein structures
 List the major components of a nucleotide, and describe
how these
 monomers are linked to form a nucleic acid.
 Explain several common functions of macromolecules
Macromolecules
THE FOUR CLASSES OF BIOLOGICAL MOLECULES
 Lipids
 Saturated, unsaturated, trans fats
 Phospholipids
 Steroids

 Carbohydrates
 Monosaccharides, glucose galactose fructose
 Disaccharides sucrose (table sugar) maltose lactose
Glycosidic bond
 Oligosachharides 3 TO 10
 Polysaccharides 10 ABOVE --- Glycogen cellulose

 Proteins
 Amino acids
 Primary, secondary, tertiary, quarternary structure

 Nucleic acids
 Nucleotides
 DNA and RNA
Natural
Sugar acids are not natural (made by reaction)

phosphoproteins are not natural

Also in naturally occurring amino acids

What do they do?
These are the most imp but there are more

 Lipids- e.g Fat

function -Cell membranes, energy storage
 Carbohydrates e.g. Starch, sugar
function -Energy storage, structure
 Nucleic acids e.g. DNA, RNA
function -Store genetic material
 Proteins e.g albumin
function-transport, structural support
Formation of a
macromolecule
 Macromolecules are
polymers composed of
thousand of monomers
joined together
e.g.
One glucose molecule alone
is a monomer
Many glucose molecules
linked together can make a
polymer
 Synthesis of polymers

Join 2 monomers
Dehydration reaction

Two glucose molecules can join together by losing a molecule

of water-
 Breakdown or digestion of
polymers

Split 2 monomers
Hydrolysis Breaking any polymer
A polymer can be broken down to its monomers by addition of
a water molecule
Carbohydrates
 Sugars and the polymers of sugars
 Simplest carbohydrate monomers are
monosaccharides
 More complex carbohydrate polymers are called
polysaccharides
 Organic compounds with a 1:2:1 ratio between
Carbon, Hydrogen and Oxygen.
 ( CH2O)
 Monosaccharides (simple sugars) C6H12O6 glucose,
deoxyribose, and ribose sugar
 Disaccharides (two sugars joined ) -The bond
between two monosaccharides is called a glycosidic
bond e.g sucrose and lactose and maltose
 Polysaccharides (complex sugars) starch, cellulose,
and glycogen
Cont..
 Organic compounds with a 1:2:1 ratio
between Carbon, Hydrogen and Oxygen.
( CH2O)
 Monosaccharides (simple sugars) C6H12O6
glucose, deoxyribose, and ribose sugar
 Disaccharides (two sugars joined ) -The bond
between two monosaccharides is called a
glycosidic bond
sucrose and lactose and maltose
 Polysaccharides (complex sugars) starch,
cellulose, and glycogen
Cont..

CHO

C=O

MOST COMMON TYPE

 Monosaccharides
Position of OH in C1 for alpha or beta

In nucleic acid RNA and DNA

 Disaccharides
Alpha or Beta

LACTOSE
Lactose intolerance
 Inability to digest the sugar in milk
 Caused by a lack of the enzyme lactase,
which hydrolyzes lactose into its
monosaccharides glucose and galactose
 Bacteria in your gut can metabolize it
through fermentation though, which
produces hydrogen, carbon dioxide, and
methane
reason for nausea and vomiting
Polysaccharides
 Many monosaccharides linked together through glycosidic bonds
 The structure and function of a polysaccharide are determined by its sugar
monomers and the positions of glycosidic bonds
 Two types of polysaccharides:
Storage
 Starch- unbranched chain of glucose found in plants. Consists of α 1,4
glycosidic bonds
 Glycogen-Branched chains of glucose found in animals ( liver and muscle).
Consists of α 1,4 and α 1,6 glycosidic bonds. The highly branched
structure permits rapid glucose release from glycogen stores, e.g., in
muscle during exercise
Structural
Cellulose -β 1,4 glycosidic bonds.The polysaccharide cellulose is a major
component of the tough wall of plant cells
Like starch, cellulose is a polymer of glucose, but the glycosidic linkages
differ
What is a fiber ?

 Enzymes that digest starch by hydrolyzing

alpha linkages can’t hydrolyze beta
linkages in cellulose
 Cellulose in human food passes through the
digestive tract as insoluble fiber
 Some microbes use enzymes to digest
cellulose
 Many herbivores, from cows to termites,
have symbiotic relationships with these
microbes
Cont..

 Chitin is in the exoskeleton of arthropods and the cell walls of many fungi
Lipids
 The only class that does not form polymers bec they are large molecules and cant join together

 Lipids are hydrophobic because they consist mostly of hydrocarbons,

which form nonpolar covalent bonds
 The most biologically important lipids are fats, phospholipids, and
steroids
 Purpose: fuel storage, cell membranes insulation
Cont..
Triglycerides
IN OUR FOOD

 Two components: glycerol and 3 fatty acids

 The major function of fats is energy storage

The hydrogen on this hydroxyl group can

be removed off in water. Since the
molecule is donating a hydrogen, it is
sugar alcohol classified as an acid
small or large is based on C
Synthesis

DIFFERENT FATTY ACIDS CAN JOIN THE GLYCEROL

 Types
 Saturated fatty acids have the Block blood vessels and not healthy to be eaten
maximum number of hydrogen
atoms possible and no double
bonds. Each carbon ‘saturated’
with hydrogens
Because they are so densely
packed, saturated fats tend to be
solid at room temp. A group of
identical and regular molecules fits
together more neatly than different
and irregular molecules”
Triglycerides circulate in your blood.
Saturated and trans fats clump
together much more easily in your
blood vessels, forming plaque that
blocks arteries
 Unsaturated fatty acids have one
or more double bonds liquid or semi solid at RT
 The hydrocarbon chains don’t stack so easily, and so are less unsoluble
 Monounsaturated and Polyunsaturated
Non-essential fatty acids are produced by the body

 Monounsaturated fats have only one carbon-carbon

double bond
 Polyunsaturated fats have two more more carbon-
carbon double bonds
 Essential fatty acids -Certain unsaturated fatty acids
are not synthesized in the human body, and must be
supplied in the diet
 These essential fatty acids include the omega-3 fatty
acids, required for normal growth, and thought to
provide protection against cardiovascular disease
3, 6, 9, 12, 15
20
KNOW NAMES
NO STRUCTURE
Between 12-13
Hydrogenated fats
 Produced by artificially saturating
unsaturated fats by adding hydrogen –
“hydrogenation”
–Hydrogenation also straightens the kinks in
unsaturated fats, isomerizing from cis to trans
form
Partially hydrogenated vegetable oil: some of
the carbon-carbon double bonds are
hydrogenated, but not all

Unsaturated TO saturated
Cont…

 Saturated fats tend to be solid at room

temp
–In baked goods, saturated fats produce a much
better “mouth feel” and texture than unsaturated
fats
–Cheaper to hydrogenate the polyunsaturated fats
in vegetable oil than acquire natural saturated fats
from animal sources
•Saturated fats are more stable than unsaturated
fats
–Beef has a longer shelf life than chicken because
it has a larger proportion of saturated fats
Steroids and phospholipids
 Steroids
 Cholesterol
 Hormones
 Phospholipids
 Two fatty acids and a phosphate group
 Fatty acids are hydrophobic
 Phosphate group is hydrophilic
 Major component of cell membrane
 Proteins- A polymer of
Amino acids
 C, H, O, N, sometimes S
 Monomer is – amino acids
 20 different
 Each amino acid contains
 an amino group (NH2)
 Central Carbon (C)
 H some could contain sulfur
joined by peptide bond (CONH)
 Carboxyl group (COOH)
 Unique “R” group Dipeptide= 2 amino acids joined together by
peptide bond (Whole structure of amino acid)
ONLY KNOW
NAMES AND
"naturally occurring"
CLASSIFICATION

2 are modified (Hydroxyproline and Cystine)

 H bond
Twisted (Alpha
helix) or like a
single sheet (B pleated
peptide sheet)
bond

3-D structure
more twists and more
bonds (Spherical)
helical
NO sub-units

Sub-units joined together (Polypeptides)

3-D structure
Types of proteins
 Primary- consists of amino acids joined by peptide bond

 Secondary
 Tertiary-
3D
globular

Quaternary- consists
of 2 or more
3D globular structures
Peptide bonds
 A. Amino acids in peptides are covalently linked

1. This bond is referred to as a peptide bond

2. It is formed by a dehydration synthesis reaction
 Dipeptide- Two amino acids linked together
 Oligopeptide- 3-10 amino acids linked together
 Polypeptide-several aminoacids linked together
( more than 10)
 Functions
 Some proteins, such as insulin, are hormones
 Some proteins, like keratin, are structural
proteins
 Actin and myosin fibers in muscle cells,
spider webs, and silk are also structural
proteins
 Some proteins are enzymes that build or
break down other molecules in living cells
 Some proteins are structured to carry or
move substances, such as hemoglobin that
carries oxygen, or cell membrane proteins
that move substances across the membrane
Nucleic Acids Genetic material

 Made up of smaller units called nucleotides (sugar,

phosphate and nitrogenous base) purine / pyrmidine
 DNA (Deoxyribonucleic acid) Nucleotide= sugar + nitrogenous base + Phosphate group
 Double Helix ( twisted ladder) Ribose / Deoxyribose

 Contains the bases A, T, C, & G

 Contains the code for the bodies proteins. DNA is the
hereditary material passed on from parents to
offspring
 RNA (Ribonucleic acid)
 Single strand
 Contains the bases A, U, C, & G
 Carries the code for a protein, and transfers amino
acids to the ribosomes.
Uracil
RNA and DNA
RNA –single stranded A - T (2 H bonds)
C - G (3 H bonds)

DNA-double stranded
MLS 218
CHS
Objectives
• Describe and discuss three stages of metabolism
• Describe various pathways of carbohydrate metabolism- both anabolic and
catabolic
• Differentiate between glycogenesis and glycolysis ,gluconeogenesis
• Explain TCA cycle.
• Give conditions for conversion of pyruvate to lactate, ethanol and acetyl
CoA
• Calculate the total number of ATP formed
• Enumerate and explain different types carbohydrate metabolism disorders
e.g glycosuria, different types of diabetes ,its complication and lab
investigations
• Discuss hormonal control of blood sugar level
• Interpret laboratory data
• Explain the relationship between carbohydrate, lipid and protein metabolism
 Metabolism
CHS
digestion is the physical breakdown of larger molecules into smaller units
after absorption, molecules travel in blood stream to cells where metabolism occur to provide energy

 What is metabolism?
 Is the sum total of all the chemical ( enzymatic ) reactions
Involved in maintaining the living state of the cells/organisms
Carbohydrates digestion starts in the mouth (Amylase break starch) after digestion, should be
converted to glucose for energy. If not possible by digestion, the other monosaccharides taken to
liver to convert it to glucose (Fructose)
HUMAN BODY CAN ONLY UTILIZE D-GLUCOSE FOR ENERGY

Proteins = Amino acids

Carbohydrates= glucose
Fats= Fatty acids + Glycerol

 Why do living organism require energy?

 to synthesize large molecules from small ones
 to move substances in and out of cells
 muscle contraction and cell movement
 Metabolism
CHS

Two types of chemical reactions that occur in the cells of our

bodies :

1. Catabolic reactions catabolic

 Break down large molecules
 Provide energy foras ATP

anabolic
2. Anabolic reactions
 Use small molecules to build large ones
Carbohydrates
 Require energy Glucose (6C) Fatty acid
Amino acids
Carbohydrates break down fast to produce energy L ATP glycolysis
The best source of energy
Pyruvate
different stages
Lactate Acetyl CoA
4 H ATP
Electron transport chain/
Oxidative phosphorylation
 Stages of Metabolism
CHS

Catabolic reactions are organized as:

Stage 1: Digestion and hydrolysis break down
large molecules to smaller ones that
enter the bloodstream
Stage 2: Degradation breaks down molecules to
two- and three-carbon compounds glycolysis (Up to the synthesis
of pyruvate in the cytosol)
Stage 3: Oxidation of small molecules in the
citric acid cycle and electron transport
provides ATP energy

5
NADH is also producing ATP by entering electron
transport chain/oxidative phosphorylation
(INDIRECT ATP production)
CHS

DIRECT ATP
Glycolysis
in cytosol with
production
oxygen ADP+P= ATP

Glycolysis in
mitochondria
with no
oxygen
 ATP and Energy
CHS
irreversible reaction can become reversible by using different enzyme
reversible use the same enzyme to reverse
Adenosine triphosphate (ATP)
 is the energy form stored in cells
 is obtained from the oxidation of food
 consists of adenine (nitrogenous base), a ribose sugar, and
three phosphoryl groups
 During oxidation ATP is formed ADP and Pi

ADP + Pi Energy ATP DIRECT production

Catabolic

 Energy is provided by the hydrolysis of ATP

ATP ADP + Pi Energy
Anabolic
7
 Digestion of Carbohydrates
CHS

Fructose and
galactose will
go to the
liver to be
converted to
glucose to be
used for
energy
CHS

SKIP
 Fates of the absorbed glucose
CHS

• Glucose is absorbed through portal blood to the liver.

 Fructose and galactose are converted to glucose in the liver.

 The only sugar utilized by the body is glucose.

 The majority of it is taken by the liver to be stored as glycogen or

oxidized by glycolysis for acetyl CoA and lipid synthesis.

 A minimal amount passes through systemic circulation to maintain

blood sugar level in fasting conditions (the fasting blood glucose
level 70 – 110 mg/dl).


Fasting blood sugar
2 hrs post breakfast (Less than 140 mg/dl)
RBS "Random Blood Sugar" (more than 200 mg/dl diabetic) less than 200
mg/dl in normal
 Integration of carbohydrate. Lipid and protein
metabolism
glucose is needed by the brain
CHS GO to the brain for energy but when absent, ketone bodies
(when glucose is absent)
irreversible provide energy to the brain bec
they can cross the barrier
HMP reversible with different enzyme stored mainly in
Nucleic Ribose5P and kidneys liver sometimes
acid hexokinase
muscles
enzyme

occurs in the liver when there is

less glucose "Carbs"

for anabolic pathways to get energy

if glucose not converted to
glucose 6-phosphate in an
irreversible reaction then
glycolysis cant occur

connected both ways

also can produce energy can be formed from amino acids (Proteins
breakdown/synthesis)
fats are used to produce energy and to
produce ketone bodies

When ketone bodies are not used bec they are

when there is more glucose and no more capacity acidic (Extra) are harmful "Diabetes"
in liver, it is converted to Acetyl-coA. When there is
more Acetyl-coA, TCA cant accept all so it will be
converted to fats
 Major Metabolic pathways of carbohydrate
CHS
metabolism

METABOLIC PATHWAY- is a sequence of reactions catalyzed by

a number of enzymes and in which a precursor is converted to a
product. The pathway can be linear, spiral or cyclic

 Glycolysis
 Gluconeogenesis
 Citric Acid Cycle (Krebs Cycle)
 Glycogen Metabolism
 Electron Transport Chain
 Oxidative Phosphorylation
 Pentose-Phosphate Shunt
CHS
Oxidation of Glucose
10 reactions in glycolysis Anaerobic glycolysis

Aerobic glycolysis

Pyruvate (Lactate) in humans

Ethanol (in Microorganisms)

Complete oxidation of glucose has 3 processes:

- Glycolysis
- Citric acid cycle
- Electron transport chain
 Glycolysis
CHS Sequence of 10 reactions

Glycolysis Catabolic pathway because release energy (Breakdown)

 Is also called Embden-

Meyerhoff pathway
 is a metabolic pathway that
uses glucose, a digestion
product
 degrades six-carbon glucose
molecules to three-carbon
pyruvate molecules AcetylCoA (2 carbon molecules)

1 Glucose (6 carbons) = 2 pyruvate (3 and 3)

14
 Stages of Glycolysis
CHS

1. Stage one (the energy requiring stage): Reactions 1-5

a) One molecule of glucose is converted into two molecules of
glycerasldhyde-3-phosphate. 2 pyruvate

b) These steps requires 2 molecules of ATP (energy loss)

2. Stage two (the energy producing stage(: Reactions 6-10
a) The 2 molecules of glyceraaldehyde-3-phosphate are
converted into pyruvate (aerobic glycolysis) or lactate (anaerobic
glycolysis)
Acetyl-CoA = Aerobic glycolysis

b) These steps produce ATP molecules (energy production).

CHS
Overview of carbohydrate metabolism

 When glucose enters a cell from the bloodstream, it is

immediately converted to glucose 6-phosphate.
 glucose is trapped within the cell because phosphorylated
molecules cannot cross the cell membrane.
 formation of glucose-6-phosphate is not reversible in the
glycolytic pathway, thereby committing the initial substrate
to subsequent reactions.
 Glucose-6-phosphate can enter the pentose phosphate
pathway. This multistep pathway yields two products of
importance to our metabolism.
CHS
Overview of carbohydrate metabolism

 One is a supply of the coenzyme

NADPH, a reducing agent that is
essential for various biochemical
reactions.
 The other is ribose 5-phosphate, which is
necessary for the synthesis of nucleic
acids (DNA and RNA).
 Glucose-6-phosphate enters the pentose
phosphate pathway when a cell’s need for
NADPH or ribose-5-phosphate exceeds
its need for ATP.
CHS
Overview of carbohydrate metabolism
 When cells are already well supplied with glucose, the excess
glucose is converted to other forms for storage: to glycogen, the
glucose storage polymer, by the glycogenesis pathway, or to
fatty acids by entrance of acetyl-CoA into the pathways of lipid
metabolism rather than the citric acid cycle.
 When energy is needed, glucose 6-phosphate undergoes
glycolysis to pyruvate and then to acetyl-CoA, which enters the
citric acid cycle.

18
CHS

For reaction 1, if enzyme to convert glucose to G6P is not there,

glycogen can be used to produce ATP (Glycogenolysis)

3 IS THE MAIN= F-1,6BP will not be produced if the enzymes are

not available and ATP cant be produced in the later reactions

For reaction 10, there is already production of ATP in other

reactions before
CHS
Stage 1 of Glycolysis no need for structure

Oxidative phosphorylation -- ATP is produced

MOSTLY DHAP converts to glyceraldehyde-3-phosphate

All DHAP in our body in converted to glyceraldehyde-3-phosphate

loss of USES 2 ATP

one 1
phosphate

bis= means "di"

but bec in same
position called
bis

2
4

ketose

can convert to each

other by

3 5
Triose phosphate
isomerase
DHAP
2 G-3P converted to 2 pyruvates
coverts to Pyruvate
CHS
Stage 2 of Glycolysis
2 NADH produced, 4 ATP produced
Net energy gain= 2 NADH, 2 ATP

Produced from G-3-p 6

direct production of ATP 8

reaction called:
substrate level
phosphorylation 9
SEE
Phosphate
taken from the
molecule and
9 SAHAR
7
given to ATP PIC
glycolysis

2NAD to 2NADH
10
8 10

2NAD 2NADH

Lactate is not produced= Energy not produced bec it is converting NADH to NAD that is used in Lactate Pyruvate
glycolysis
CHS Glycolysis: Overall Reaction
When NADH enters ETC and ADP is phosphorylated to
produces ATP = Oxidative phosphorylation
In glycolysis,
 two ATP add phosphate to glucose and fructose-6-phosphate
 four ATP are formed in energy generation by direct transfers
of phosphate groups to four ADP
 there is a net gain of 2 ATP and 2 NADH

Cytosolic NADH (the 2 NADH produced) 22

NADH in cytosol should enter mitochondria for ETC by 2 processes (Transport NADH as
NADH) (Transports it as FADH) and cause phosphorylation of ATP
 1 Regulatory steps
CHS irreversible

Why does glycolysis reversible

DHAP must be converted
result in 2 Pyruvte into G-3P via the enzyme
molecules? 3 triose phosphate isomerase to
proceed through glycolysis

G-3P DHAP

3 irreversible reactions (1, 3, 10) =

regulatory steps of the pathway
(Control)

DEPENDING ON THE NEED OF

ATP, these reactions are controlled
(Fast/slow)

The main regulatory reaction (3) has

the main regulatory enzyme

10
 For reaction 1, if enzyme to convert glucose to G6P

Regulation of Glycolysis
is not there, glycogen can be used to produce ATP
(Glycogenolysis)

CHS 3 IS THE MAIN= F-1,6BP will not be produced if the

enzymes are not available and ATP cant be
produced in the later reactions
Glycolysis is regulated by three enzymes: For reaction 10, there is already production of ATP
in other reactions before
 In Reaction 1, hexokinase is inhibited by high levels of glucose-6-
phosphate, which prevents the phosphorylation of glucose.(is not key
because of G6P is generated by glycogenolysis)

 In Reaction 3 (Main key reaction), phosphofructokinase, an

allosteric enzyme, is inhibited by high levels of ATP and activated by
high levels of ADP and AMP. This reaction is called the rate limiting
step of glycolysis

 In Reaction 10, pyruvate kinase, another allosteric enzyme is

inhibited by high levels of ATP or acetyl CoA. .(is not key because
this reaction is reversed in gluconeogenesis)
24
CHS
Substrate level phosphorylation
In glycolysis, what compounds provide phosphate groups for the
production of ATP?

In reaction 7, phosphate groups from two

1,3-bisphosphoglycerate molecules are transferred to
ADP to form two ATP.

In reaction 10, phosphate groups from two

phosphoenolpyruvate molecules are used to form two
more ATP.
NET GAIN= 2 ATP
Production= 4 ATP
2 are used in the reaction so (4 - 2 = 2) 25
CHS
Pathways for Pyruvate IN ANAEROBIC CONDITION

help in the continuation of glycolysis NAD

2nd stage
NADH

GLYCOLYSIS NADH
NAD+

LACTATE

IN AEROBIC
O2 is imp here
NADH enters ETC and then converts to NAD+

help in the
continuation of
glycolysis

FAD also enters ETC not at

transported to mitochondria as NADH or FADH (Humans=NADH) (Some other org= FADH) the beginning and can
cause phosphorylation of 2

Cytosolic NADH 26 ATP

Enters ETC for ATP (Form NAD+ "Oxidation") ---- ADP +Pi "Phosphorylation " (3 times)
Mitochondrial NADH
all give 3 ATP 1 NAD+ = 3ATP in ETC 1 FAD+ = 2 ATP
CHS Pyruvate: Aerobic Conditions
1 NADH ---- (Enters ETC at the beginning) ---- (ADP + Pi) (ADP + Pi) (ADP + Pi) = 3 ATP

Under aerobic conditions (oxygen present),

 three-carbon pyruvate is decarboxylated
 two-carbon acetyl CoA and CO2 are produced

Also produces NADH

To calculate energy, LOOK AT:

- ATP used
- ATP produced
- NADH produced
- FADH produced

27

Pyruvate is converted to Acety CoA in mitochondria (Pyruvate moves to the mitochondria "whole reaction inside")
 Pyruvate: Anaerobic Conditions
CHS
Under anaerobic conditions (without oxygen),
 pyruvate is reduced to lactate
 NADH oxidizes to NAD+ allowing glycolysis to continue

28
CHS Lactate in Muscles

 Strenuous exercise leads to anaerobic conditions

 Oxygen in muscles is depleted
 Lactate builds up as glycolysis continues
 Muscles tire and become painful
 Breathing rate increases
 Rest repays oxygen debt
 Lactate re-forms pyruvate in liver
Active muscle Liver
Glucose Glucose
Glycogen
pyruvate Pyruvate
lactate Lactate Glucogenesis
Cori cycle: Happens only when muscles are active bec they are producing 29
lactate and move in blood to the liver
 Conversion of Pyruvate to Ethanol
CHS
 Anaerobic microorganisms such as yeast, convert pyruvate to
ethanol by fermentation
- pyruvate is decarboxylated to acetaldehyde, which is
reduced to ethanol
- NAD+ is regenerated to continue glycolysis

 The CO2 produced during fermentation make the bubbles in

beer and champagne, and also makes bread rise

O H+ CO2 NADH + H+ NAD+

O
O
OH
pyruvate H alcohol
O decarboxylase dehydrogenase
Pyruvate Acetaldehyde Ethanol
 Cori Cycle
CHS

The Cori cycle

 is the flow of lactate and glucose between the muscles
and the liver
 occurs when in active muscle and glycolysis produces
lactate
 operates when lactate moves through the blood stream
to the liver, where it is oxidized back to pyruvate
 converts pyruvate to glucose, which is carried back to
the muscles

31
CHS
Cori Cycle

32
Pyruvate can give ATP when not exercising (Pyruvate will not convert to glucose, it will
be converted Acetyl CoA)
CHS Transport of cytosolic NADH
The inner membrane is impermeable to hydrophilic substances. Has
special transport systems for the following:
1. Glycolytically produced cytosolic NADH.
2. Mitochondrially produced metabolites (OAA, acetyl-CoA) for
cytosolic glucose formation and fatty acid biosynthesis.
3. Mitochondrially produced ATP must go to cytosol where ATP-
utilizing reactions take place
 Example: cytoplasmic shuttle systems transport NADH across inner
membrane
 The glycerol phosphate shuttle is a secondary mechanism for the
transport of electrons from cytosolic NADH to mitochondrial
carriers of the oxidative phosphorylation pathway.
 The primary cytoplasmic NADH electron shuttle is the malate-
aspartate shuttle. NADH = 3 ATP
FADH = 2 ATP
CHS
Glycerol Phosphate Shuttle
Secondary mechanism
 Uses an enzyme glycerol -3- phosphate
dehydrogenase
Dihydroxyacetone phosphate + NADH =----(glycerol-3-phosphate dehydrogenase)----= NAD+ + Glycerol-3-phosphate
Glycerol-3-phosphate + FAD =----(flavoprotein dehydrogenase)----= FADH2 + dihydroxyacetone phosphate from glycolysis
FADH2 -------- ETC

 Dihydroxyacetone phosphate in the cytosol is

reduced to glycerol-3-phosphate as NADH is
oxidixed to NAD+ combines

From glycolysis
 The electrons of glycerol-3-phosphate are
transferred to FAD (yielding FADH2) and
DHAP is produced.
converts FAD to FADH

 During this reaction the electrons in FADH2

are transferred directly to the electron
transport chain
NADH + DHAP
FADH ETC

NAD+ + Glycerol-3-phosphate

more energy in NADH than FADH

 Malate aspartate shuttle
CHS
 NADH is oxidized by oxaloacetate. This Primary mechanism
yields malate (carries electrons). usually this happens

 The malate - alpha-keto-glutarate carrier

transports malate into matrix and
keto acid amino acid
transports alpha-keto-glutarate out.

 In matrix, electrons from malate

transferred back to NAD+ , reformation of
NADH. Malate is consequently oxidized to
OAA.
NADH enters mitochondria as malate (not another one)

 Transamination of OAA by Glutamate

yields Aspartate and alpha-keto-glutarate.

 Aspartate is transferred out of the matrix in

exchange for glutamate from the cytosol. a-ketoglutarate + Aspartate = Glutamate + (Oxaloacetate + NADH)
=NAD+ + (malate enters mitochondria) = Malate + NAD+ = NADH +
Oxaloacetate ...........
CHS
Why is glucose stored as glycogen?

 Glucose is in liquid form. As the number of

glucose molecules increases, the pressure
inside the cell increases.

 Converting glucose to glycogen

(in solid form) relieves pressure inside the
cell.
CHS
Glycolysis:
Specific tissue functions
 RBC’s
 Rely exclusively for energy-Mature RBCs contain no
mitochondria, thus depend only upon glycolysis for energy
production
 Skeletal muscle
 Source of energy during exercise, particularly high intensity
exercise
 Adipose tissue
 Source of glycerol-P for TG synthesis
 Source of acetyl-CoA for FA synthesis
 Liver
 Source of acetyl-CoA for FA synthesis
 Source of glycerol-P for TG synthesis
CHS
Glycolysis: General Functions
 Provide ATP
 Generate intermediates for other pathways
• Hexose monophosphate pathway
• Glycogen synthesis
• Fatty acid synthesis-Dihydroxyacetone phosphate: can give glycerol-
3phosphate, which is used for synthesis of triacylglycerols and
phospholipids (lipogenesis). Also pyruvate (From glycolysis) then AcetylCoA is formed to be converted to
fatty acid
• Pyruvate which give acetyl CoA for Krebs’ Cycle
• 3 Phosphoglycerate: which can be used for synthesis of amino acid serine.
• Pyruvate: which can be used in synthesis of amino acid alanine

protein synthesis
Glycolysis is also involved partially in protein metabolism
 Glycogenesis
CHS
Excess glucose leading to excess glucose-6-phosphate
 Liver and muscle store glucose by converting glucose to
glycogen 2nd option to convert to glycogen bec 1st is giving ATP (energy)
 operates when high levels of glucose-6-phosphate are
formed in the first reaction of glycolysis
 does not operate when energy stores (glycogen) are full,
which means that additional glucose is converted to body fat
 Muscle glycogen- provides glucose (glucose 6-PO4) for
glycolysis
 Liver glycogen- provides glucose to maintain blood
glucose level
Normally, insulin and absorption maintain blood glucose level, but in fasting, no hormones or
starvation then the liver takes place for the production of glucose from glycogen
39
 Diagram of Glycogenesis
CHS when 10 glucose are attached (With alpha 1,4 glycosidic bond) by glycogen synthase, then branching glucose will add one branch (With alpha 1,6 glycosidic bond)

happening
again and
again
add free
glucose
molecules

First reaction of glycolysis

40
CHS
Glycogenolysis
In glycogenolysis,
 glycogen is broken down to
glucose
 glucose molecules are
removed one by one from the
Glycogenesis
end of the glycogen chain to Glycogenolysis

yield glucose-1-phosphate

41
CHS
Glycogenolysis

 Glycogen phosphorylase
removes most glucose residues
as Glc-1-P
 Molecules left after complete
only from the spread chain (Straight) in the
form of glucose-1-phosphate
phosphorylase digestion of
glycogen are Limit Dextrins
will form 6 "Glucose-1-phosphate" as it will remove 6 from the chain
4 will left as it cannot go bypass (Limit Dextrins)

less glucose are here (Not 10), we should call this structure Limit Dextrins
CHS
Glycogenolysis
"Debranching enzyme" having different  1. a-1,4->1,4 Glucosyl
activities that are mentioned here
transferase activity transfers
three residues to another chain
 2. Amylo a-1->6 Glucosidase-
hydrolytic activity releases Glc
 Major Final Product of
to remove the branched ones
It cuts 3 only and joins them to the
spread (unbranched) chain
Glycogen Degradation is Glc-1-
P
 To Complete Glycogen
Degradation, Need to Convert
It is a free glucose molecule
it wont be added to the straight chain
Glc-1-P to Useful Form
CHS
Glycogenolysis
Glycogenolysis
 is activated by glucagon (low blood glucose)
 bonds glucose to phosphate to form glucose-1-phosphate
Glycogen-glucose + Pi glycogen + glucose-1-phosphate

44
CHS
Isomerization of Glucose-1-Phosphate
 In the muscle ,The glucose-1-phosphate isomerizes to glucose-6-
phosphate, which enters glycolysis for energy production.

in the muscles OR if u need

energy
glucose production mostly occurs when brain
requires energy

45
CHS Glucose-6-Phosphate
Glucose-6-phosphate
 hydrolyzes to glucose in the liver and kidney, where
glucose-6-phosphatase is available, providing free glucose
for the brain and skeletal muscle

only in liver and kidney

46
CHS

Uridine diphosphate
 know the number, eponym (Name), enzyme deficiency, lab findings
CHS
 Gluconeogenesis
CHS
 Is the synthesis of
glucose from carbon
atoms of
noncarbohydrate
compounds
 required when glycogen
4 enzymes are needed to reverse
stores are depleted the irreversible reactions of
glycolysis in gluconeogenesis

from lactate or pyruvate, they are converted to glucose

when glycogenolysis isnt possible bec no glucose
2 enzymes for reaction 10
which is 2 here
 Gluconeogenesis
CHS
In gluconeogenesis,
 glucose is synthesized from noncarbohydrates such as lactate, some
amino acids, and glycerol after they are converted to pyruvate or
other intermediates
 seven reactions are the reverse of glycolysis and use the same
enzymes
 three reactions are not reversible. The three steps to be bypassed
are:

1. glucose + ATP glucose-6-phosphate + ADP

3. fructose-6-phosphate + ATP fructose-1,6 -
bisphosphate + ADP
10. PEP + ADP pyruvate + ATP
50
 Gluconeogenesis: Pyruvate to
CHS Phosphoenolpyruvate
 Pyruvate is converted oxaloacetate by two reactions that replace the
reverse of reaction 10 of glycolysis.

51
 Gluconeogenesis:Phosphoenolpyruvate to
CHS
Fructose-1,6-bisphosphate
 Phosphoenolpyruvate is converted to fructose-1,6-
bisphosphate using the same enzymes in glycolysis.

(RED ARROWS) = same enzymes as glycolysis

(BLUE) = Different

52
CHS
Glucose Formation
 fructose-1,6-bisphosphate forms fructose-6-
phosphate and Pi with help of enzyme frucose -6-
bisphosphatase
 a reversible reaction converts fructose-6-phosphate
to glucose-6-phosphate
 G -6 Phosphate is converted to glucose with the help
of enzyme glucose-6-phosphatase

53
 Glycolysis and gluconeogenesis
CHS
CHS
CHS
Comparison of Regulation of Glycolysis
and Gluconeogenesis
some of the regulatory factors are working
against each other

reversed

example of Reciprocal control of

glycolysis and
gluconeogenesis "working against
each other"

means low energy

56
Glycolysis is complete
CHS
Reciprocal control of glycolysis and
gluconeogenesis
CHS
Citric Acid Cycle

The citric acid cycle

Also call TCA ( Tri carboxylic acid cycle)
OR KREB’s cycle
 operates under aerobic conditions only in mitochondria

 oxidizes the two-carbon acetyl group in acetyl

CoA to 2 CO2
 produces reduced coenzymes NADH and
FADH2 and one ATP directly

58
 Summary of the Citric Acid Cycle
CHS

In the citric acid cycle,

 an acetyl group bonds with oxaloacetate to form citrate
 two decarboxylations remove two carbons as 2 CO2
 four oxidations provide hydrogen for 3 NADH and one FADH2
Pyruvate==(O2)==Acetyl CoA + OAA Citrate
 a direct phosphorylation forms GTP (ATP)

59
CHS Summary of the Citric Acid Cycle
1. Pyruvic acid is converted to acetyl CoA in three main steps.
• Decarboxylation.
• Oxidation.
• Formation of acetyl CoA.
KNOW WHAT IS PRODUCED IN EACH REACTION
2. An eight step cycle generating:
• Three molecules of NADH + H+.
• One molecule of FADH2.
• Two molecules of CO2
• One molecule of ATP.
6NADH 2FADH2 2ATP 4CO2

• For each molecule of glucose entering glycolysis, two

molecules of acetyl CoA enter the Krebs cycle.
CHS
Regulation of Citric Acid Cycle

The reaction rate for the citric acid cycle

 increases when low levels of ATP or NAD+
activate isocitrate dehydrogenase and also
increases the synthesis of acetyl Co A
 decreases when high levels of ATP or
NADH inhibit citrate synthetase (first step
in cycle) and also reduces the formation of
acetyl Co A

61
 TCA cycle is at the intersection of carbohydrate,
CHS
lipid and protein metabolism

Carbohydrates: Acetyl CoA entering the cycle is produced from

pyruvate.
Fatty acids: Acetyl CoA entering the cycle may be produced as a
product of β-oxidation of fatty acids.

Amino acids: Acetyl CoA is also produced by metabolism of the

amino acids leucine and tryptophan.
Other amino acids are converted to other intermediates of the TCA
cycle or pyruvate.

the common pathway that they enter is the citric acid cycle
CHS
Link between carbohydrate,lipid and
protein metabolism

enter in different stages

RED are the intermediate of the citric acid cycle "What is formed throughout the pathway"
CHS ATP from Citric Acid Cycle

One turn of the citric acid cycle provides

3 NADH  3 ATP = 9 ATP
1 FADH2  2 ATP = 2 ATP
1 GTP  1 ATP = 1 ATP
Total = 12 ATP

Because each glucose provides two acetyl CoA, two turns of the
citric acid cycle produce 24 ATPs.
2 Acetyl CoA 4CO2 + 24ATP (two turns of citric acid cycle)

64
CHS
ATP from Glucose
net gain in glycolysis= 2 ATP + 2 NADH

One glucose molecule undergoing complete oxidation

provides: Glycolysis:
2 ATP= 2ATP
From glycolysis 68 ATP 2 NADH (each NADH gives 3 ATP)== 6ATP
8ATP

From 2 pyruvate 6 ATP 2 NADH from pyruvate= 6ATP=14 TOTAL

From 2 acetyl CoA 24 ATP
From citric acid cycle:
24+14= total 38
3 NADH = 9 ATP 1 FADH= 2 ATP 1ATP=1
Because 2 acetyl CoA so = 12x2= 24 ATP

Overall ATP production for one glucose:

C6H12O6 + 6 O2 + 36 ADP + 36 Pi
Glucose 6 CO2 + 6 H2O + 36 ATP

65
CHS
Hormonal control of blood sugar
• The activity of the liver in maintaining the normal blood sugar level
is controlled by several different hormones.
• Insulin
• Epinephrine
for maintenance
• Glucagon
• Cortisol others increase or decrease the level

• Growth Hormone.
 Hormones controlling blood sugar
CHS
1. Insulin produced by pancreas, perform the following functions:

high glucose "Fed" low glucose "Fasting"

high blood sugar level Low blood sugar level
it decreases blood sugar it increases blood sugar
Hypoglycemic hormone Hyperglycemic hormone
help glucose to enter the
cell to remove it from blood

when glucose removed from the blood and enters the cell "
Utilized" (Glycolysis) if energy is required to produce ATP
CONVERTS TO GLUCOSE-6-PHOSPHATE and then to
glycogen "Glycogenesis" NO ATP needed catabolic

enough stored, then converts to fats and proteins Occur in fat breakdown
can also occur from glucose and fat breakdown but not here
anabolic

Also occurs: intermediates of TCA are made up of proteins and thus protein synthesis could occur if no intermediates
are there, and TCA need to occur
 Hormones controlling blood sugar
CHS
• Insulin :The principle function of insulin is the removal of glucose from
bloodstream and lowering blood glucose level.
• It increases the uptake of glucose by extrahepatic tissues (heart, skeletal muscles
and adipose tissues).

• It increases utilization of glucose (oxidation, glycogenesis and lipogenesis) in

different tissues.

• It decreases out put of glucose by liver(decreases glycogenolysis and

gluconegenesis).
 A simplified view of the mechanism of insulin
CHS

insulin can be thought of as the

funnel that allows glucose to
pass through the receptors into
cells.
S= SUGAR (glucose)
CHS
 Hormones controlling blood sugar
CHS
2. Glucagon, its effect is opposite to insulin.
• Glucagon rises blood sugar level, by enzyme phosphorylase in liver,
glycogen converted to glucose. ( increases Glycogenolysis)
• Glucagon also increases gluconeogensis from amino acids and lactic
acid.
• Increasing protein and fat breakdown. NORMAL breakdown to get ATP

GLYCOGENOLYSIS, GLUCONEOGENISIS,
FAT BREAKDOWN...........
CHS Insulin verses Glucagon

Insulin
Glucagon
+
-
glycolysis
Glucose Pyruvate

gluconeogenesis
-
+ -

Glucagon Insulin
 Glucose homeostasis
CHS EXTRAHEPATIC CELLS= it is utilized "Glycolysis (Glucose oxidation)"
Body
cells
2 sites of action take up more
Insulin glucose

Beta cells
of pancreas stimulated
to release insulin into
the blood Liver takes Blood glucose level
up glucose declines to a set point;
High blood and stores it as stimulus for insulin
glucose level glycogen release diminishes

STIMULUS:
Rising blood glucose
level (e.g., after eating
a carbohydrate-rich Homeostasis: Normal blood glucose level
meal) (about 90 mg/100 mL) STIMULUS:
AND TRIGLYCERIDES Declining blood
less than 200 glucose level
(e.g., after
skipping a meal)

Blood glucose level

rises to set point; Alpha
stimulus for glucagon cells of
release diminishes pancreas stimulated
to release glucagon
into the blood
Liver
breaks down Glucagon
glycogen and
releases glucose one site of action
to the blood
 Hormones controlling blood sugar
CHS

3. Adrenalin (Epinephrine), secreted by adrenal medulla.- Is a

hyperglycemic hormone.
• During emotional stress, anger of fright, epinephrine is released,
increases amount of glucose in blood.
• It stimulates the release of glucagon and inhibits insulin sercretion.
• Stimulate glycogenolysis in liver and breakdown of triglyceride in
adipose tissue
• This may lead to transient hyperglycemia, sugar appear in urine. (not
diabetes)- Emotional glucosuria
more than 180= glucose is seen in urine
CHS
Hormones controlling blood sugar

4.Cortisol This glucocorticoid is secreted by the adrenal cortex.

It stimulates protein catabolism, and gluconeogenesis from amino
acids.
In extrahepatic tissues, it decreases glucose utilization .

It stimulates lipolysis in adipose tisues.

Hypersecretion of glucocorticoids may produce D.M.(Steriod D.M.) as

in cushing syndrome.

D.M.may be produced by prolonged administration of cortisone or its

derivatives.
CHS
Hormones controlling blood sugar
Hyperglycemic hormone
4. Growth Hormone It is counter-regulatory hormone secreted by the
anterior pituitary gland in response to abnormal low blood glucose
level.

 It decrease utilization of glucose in many tissues and stimulates

gluconeogenesis in the liver through induction of transaminases.

 -it stimulates lipolysis in adipose tissues.

 -Hypersecretion of GH can produce DM (pituitary DM)

 Hormones controlling blood sugar
CHS

5.Thyroid hormones (TH): Thyroxine affects the blood

glucose
Is elevated in hyperthyroid patients and decreased in
hypothyroidism.
Prolonged un treated hyperthyroidism can produce DM.

Thyroxine increases all aspects of CHO metabolism by

stimulating:
 Insulin secretion and catabolism
LEAD TO
 Glucose absorption by intestine
 Glucose uptake and utilization by tissues
 Glycogenolysis and gluconeogenesis. >>increases
blood glucose Then more pressure over the pancreas and over time it will not function
properly leading to DM

most commonly performed test in clinical lab is glucose test (As it shows metabolism and many other
processes )
CHS Glycosuria
Normal human urine does not contain Glucose (Presence = Abnormality)

It is the presence of abnormal amounts of any sugar in urine.

It is futher classified according to the sugar present into the
following types:
More than 180 mg/dl of glucose, then it is seen in urine

1-Glucosuria:

It is the presence of glucose in urine in amounts detectable by

ordinary routine methods (Fehling's &Bendict's tests and urinary
strips) .
CHS
Glycosuria
not very common

2-Fructosuria
1-Alimentary fructosuria:following ingestion of
large amount of fructose.
2-Essential fructosuria due to hereditary deficiency
of fructokinase.
3-Galactosuria
1-Alimentary :following by ingestion of large amounts
of galactose,particularly in patients with hepatic
function impairment.
2-In cases of galactosemia
CHS
Causes and Types of glucosuria
A- Hyperglycemic glucosuria:
It occurs when the blood glucose level exceeds the renal threshold
(180mg/dl) and is caused by :
-Diabetes mellitus .
-Epinephrine glucosuria as emotional or stress glucosuria or in case of
pheochromocytoma (epinephrine secreting tumor).
-Alimentary glucosuria
It is due to increased rate of glucose absorption as in cases of
gastrectomy or gastrojejunostomy.
-Experimental glucosuria
a)Alloxan diabetes ;destroy the Beta cells of pancreas.
Alloxan is a toxic glucose analogue,
b)Diabetes with pancreatectomy.
CHS Causes and Types of glucosuria

B-Normoglycemic or renal glucosuria:

In these cases,the blood glucose is within normal range
1-Congenital renal glucosuria (benign glucosuria or diabetes
innocens),due to congenital defects in renal tubular mechanism
for reabsorption of glucose.

2-Acquired renal diseases as in nephritis.

3-Phlorhizin produces this type of glucosuria due to inhibition of

the sodium dependent glucose transporter in renal tubules. It is
one type of experimental glucosuria .
 Eating sugar does not cause diabetes, because pancreas is working and

CHS
Diabetes producing insulin. Diabetes mellitus starts with high blood sugar and because
of this, other issues occur. It is a group of diseases as other metabolic
disturbances are there
Once diabetic don't eat much sugar
 Diabetes mellitus (DM) is a group of diseases
characterized by high levels of blood glucose resulting
from defects in insulin production, insulin action, or
both.
 Diabetes mellitus may present with characteristic
symptoms such as thirst, polyuria, blurring of vision,
and weight loss.
 The metabolic disturbances are accompanied by loss
of carbohydrate tolerance, fasting hyperglycemia,
ketoacidosis, decreased lipogenesis, increased
lipolysis, increased proteolysis and some other
metabolic disorders
 In its most severe forms, ketoacidosis or a non–ketotic
hyperosmolar state may develop and lead to stupor,
coma and, in absence of effective treatment, death.
CHS
Types of Diabetes

 Type 1 Diabetes Mellitus

 Type 2 Diabetes Mellitus major 3
 Gestational Diabetes
 Other types:

❖LADA (

❖MODY (maturity-onset diabetes of youth)

❖Secondary Diabetes Mellitus
CHS
Type 1 diabetes
Deficiency of insulin
Treatment: Insulin injection
 Was previously called insulin-dependent diabetes
mellitus (IDDM) or juvenile-onset diabetes.
 Type 1 diabetes develops when the body’s immune
system destroys pancreatic beta cells, the only
cells in the body that make the hormone insulin
that regulates blood glucose.
 This form of diabetes usually strikes children and
young adults, although disease onset can occur at
any age.
 Risk factors for type 1 diabetes may include
autoimmune, genetic, and environmental factors.
CHS
Type 2 diabetes In adults mainly
Insulin is produced but it is
not functioning properly

 Was previously called non-insulin-dependent diabetes

mellitus (NIDDM) or adult-onset diabetes.
 It usually begins as insulin resistance, a disorder in
which the cells do not use insulin properly. Insulin isn't used so
glucose level does not
reduce, more pressure
 As the need for insulin rises, the pancreas gradually on the pancreas as it is
loses its ability to produce insulin. producing insulin

 Type 2 diabetes is associated with older age, obesity,

family history of diabetes, history of gestational
diabetes, impaired glucose metabolism, physical
inactivity, and race/ethnicity.
 Type 2 diabetes is increasingly being diagnosed in
children and adolescents.
Treatment: Tablets
but when severe then
injection
CHS
Gestational diabetes (GDM)

 A form of glucose intolerance that is diagnosed

in some women during pregnancy.
 It is also more common among obese women
and women with a family history of diabetes.Previous history of GDM
(got it before when she
was pregnant)
 During pregnancy, gestational diabetes requires
treatment to normalize maternal blood glucose
levels to avoid complications in the infant.
 for pregnant women
but could also be
CHS Gestational diabetes Mellitus done for others
Glucose tolerance test / GTP / OGTT - The most common test done to check glucose level (Fasting blood sample/ sometimes
urine), then drink glucose solution and tested in 1hr,2hr, 3hr..... intervals. Total 4 tests (Fasting blood sample, 1hr, 2hr, 3hr)
 A woman has gestational diabetes when she is
pregnant and has any two of the following: a fasting
plasma glucose of more than 105 mg/dl, a 1-hour If any 2 are high, then
glucose level of more than 190 mg/dl, a 2-hour gestational diabetes

glucose level of more than 165 mg/dl, or a 3-hour If only 1 is high, then
keep monitoring
glucose level of more than 145 mg/dl.
The glycemic control target for GDM is preprandial
▪ ≤ 105 mg/dl (5.8 mmol/L) and either
▪ 1 hr post meal ≤ 155 md/dl (8.6 mmol/L) or After
▪ 2 hr post meal ≤ 130 mg/dl (7.2 mmol/L) treatment

▪ Uncontrolled GDM is associated with spontaneous

abortion and major fetal abnormalities.
▪ In majority, GDM resolves after pregnancy but is
CHS
LADA

 Latent Autoimmune Diabetes in Adults (LADA) is a

form of autoimmune (type 1 diabetes) which is After 20 years
diagnosed in individuals who are older than the usual
age of onset of type 1 diabetes.

 Alternate terms that have been used for "LADA"

include Late-onset Autoimmune Diabetes of
Adulthood, "Slow Onset Type 1" diabetes, and
sometimes also "Type 1.5
CHS MODY
 MODY – Maturity Onset Diabetes of the Young
◦ Mutations in any one of several transcription factors
or in the enzyme glucokinase lead to insufficient
insulin release from pancreatic ß-cells, causing
MODY.
◦ Different subtypes of MODY are identified based on
the mutated gene.
 Originally, diagnosis of MODY was based on
presence of non-ketotic hyperglycemia in adolescents
or young adults in conjunction with a family history of
diabetes.
 However, genetic testing has shown that MODY can
occur at any age and that a family history of diabetes
is not always obvious.
 Secondary DM
CHS

Secondary causes of Diabetes mellitus

include:
 Acromegaly,
 Cushing syndrome,
 Thyrotoxicosis,
 Pheochromocytoma
 Chronic pancreatitis,
 Cancer
 Drug induced hyperglycemia:
◦ Atypical Antipsychotics
◦ Beta-blockers .
◦ Calcium Channel Blockers
◦ Corticosteroids.
◦ Fluoroquinolones
◦ Phenothiazines
◦ Protease Inhibitors
◦ Thiazide Diuretics
CHS
Prediabetes: Impaired glucose tolerance and
impaired fasting glucose
the timing by which diabetes can be reversed by changing diet
 Prediabetes is a term used to distinguish people who are at
increased risk of developing diabetes.
fasting and glucose tolerance test are done
 People with prediabetes have impaired fasting glucose
(IFG) or impaired glucose tolerance (IGT). Some people
may have both IFG and IGT.

 IFG is a condition in which the fasting blood sugar level is

elevated (100 to 125 milligrams per decilitre or mg/dL)

 IGT is a condition in which the blood sugar level is

elevated (140 to 199 mg/dL after a 2-hour oral glucose
tolerance test)

Every diabetic person passes through this stage but they dont know bec no
symptoms
CHS Diagnosis of diabetes mellitus
Glucose from Mg to mol = divide by 18

❑ Normal fasting plasma glucose concentration:  6.1

5.6 mmol/l
❑ Normal value of PGTT – blood glucose concentration 2 hrs
after beginning of test  7.8 mmol/l

• New criteria for diagnose of DM

1st: classic symptoms and signs of DM are present (polyuria,
polydipsia, weight loss), and increased
day-time blood glucose concentration to ≥ 11.1 mmol/l
or
2nd: fasting glucose level is 7.0 mmol/l and more for 2 days continuously like these
levels or above, then DM
or
3rd: 2 hours glucose level in PGTT is 11.1 mmol/l and more
For confirmation of diagnosis DM positivity each of the mentioned
parameters have to be re confirmed next day
CHS
Complications of Diabetes Mellitus

A. Acute complications
• Hypoglycemia
• Ketoacidosis
• Hyperosmolar hyperglycemic nonketotic coma

B. Chronic complications
• Diabetic micro- and macrovascular changes
• Diabetic neuropathy
• Diabetic retinopathy
• Diabetic nephropathy
CHS
Acute complications
1. Hypoglycemia ( 3.3mmol/l of blood glucose) - results from:
a) exogenous causes - overdose of insulin plus inadequate
food intake, increased exercise
- overdose of oral hypoglycemic agents
- alcohol
- other agents (e.g. salicylates)
b) endogenous causes - insulinoma

- extrapancreatic neoplasm (hepatomas,

tumor of GIT)
- inborn errors of metabolism (fructose
intolerance)
Symptoms and signs of hypoglycemia are caused by epinephrine release
(sweating, shakiness, headache, palpitation) and by lack of glucose in the brain
(bizarre behaviour, dullness, coma).
CHS Acute complications
2. Diabetic ketoacidosis - the most serious metabolic
complication of DM formation of ketone bodies and acidosis

Consists of the biochemical triad of hyperglycemia, ketonemia and metabolic

acidosis

– It develops when there is severe insulin insufficiency

– Insulin insufficiency triggers a complex metabolic reactions
which involve:
- decreased glucose utilisation → hyperglycemia and glycosuria

- acceleration of gluconeogenesis → hyperglycemia

- decreased lipogenesis and increased lipolysis→ increase

oxidation of free fatty acids → production of ketone bodies
(aceto-acetate, hydroxy-butyrate, and acetone) → hyperketonemia
→ metabolic acidosis → coma
CHS
Acute complications

3. Hyperosmolar hyperglycemic nonketotic coma(HHNC)

(hyperosmolar hyperglycemic syndrome) No ketone bodies
Enough insulin to inhibit fat breakdown
a) - insulin is present to some degree → it inhibits fat
breakdown → lack of ketosis
Insulin available isn't enough to remove glucose from blood
b) - insulin is present to some degree → its effectivity is
less than needed for effective glucose transport →
hyperglycemia → glycosuria and polyuria → body fluids
depletion → intracellular dehydration → neurologic
disturbancies (stupor, coma)
CHS Management of DM
 The major components of the treatment of diabetes are:

A • Diet and Exercise

• Oral hypoglycaemic
B therapy

C • Insulin Therapy
CHS
Management of DM
CHS
Hb A1c monitored in 3 months bec RBCs survive for 120 days (3 months)

Glucose in the blood binds irreversibly to a specific part of

hemoglobin in red blood cells, forming HbA1c.
The higher the glucose, the higher is the HbA1c.
HbA1c circulates for the lifespan of the red blood cell, so reflects
the prevailing blood glucose levels over the preceding 2-3
months
Risk of micro vascular and macro vascular complications of
diabetes increases as glycosylated hemoglobin increases .
HbA1c thus gives a measure of an individual’s risk of the
chronic complications of diabetes.
HbA1c are suggestive of patients management of diabetes control
measures
HbA1c for normal individuals should be between 2.4 – 4.3 %
HbA1c >6.5% is considered as possible diabetes.
HbA1c of 4.4 – 6.0 % is considered good for those having diabetes.
99
> 6.5 % is considered as poor management .
CHS

(%) (mmol /mol)

2.4 - 4.3 <20 - 23 With in reference range
4.4 - 5.3 25 – 33 Excellent
5.4 – 6.0 36 – 42 Good
> 6.5 >48 Possible diabetes
CHS
OGTT- Oral glucose tolerance test
 OGTT determines the state of carbohydrate
metabolism and is used to recognize an
early stage of diabetes mellitus.
 OGTT determines the time needed for the
concentration of glucose to return to
normal.
 the intrinsic factors such as intestinal
absorption, hormones, liver function, etc.,
influence the level of blood glucose.
 For these reasons, this test cannot be
performed in patients with gastrointestinal
disturbances.
CHS
OGTT
 The response of the body regarding the absorption and
metabolism of glucose is said to be tolerant on meeting the
normal elevation and return.
 Whereas abnormal and improper glucose metabolism is
termed glucose intolerance.
INDICATIONS
 0 –
Borderline fasting blood sugar for >2 times (~ 110
125mg/dl
 Diagnosis of Gestational Diabetes (GDM) at 24 – 28 weeks
of gestation especially for those have a family history of
diabetes.
 After delivery for those was suffering from GDM
 Patient preparation (Pre-requisites )- OGTT
CHS
 Activity--Don't smoke or exercise strenuously for 8
hours before the test or during the test.
min 8 hours, ideal 10 hours and max 12 hours

 Diet--Eat a high-carbohydrate diet (> 150 g/day) for

3 days, then fast for 10 to 12 hours
 Before the test- Don't drink coffee or alcohol for 8
hours before the test.
stop some medications that can interfere
 Drugs (medicines)-Inform the person performing
the test to omit any medications listed, as under
taking these drugs the test results may differ
(contraceptives to be stopped one cycle before the
performance of OGTT).
The test must be performed at daytime (morning).
CHS
General description of OGTT

 Test usually takes 3 hours but can last as long as 6 hours (extended
OGTT).
 The first blood sample and the first urine sample are collected
between 7 A.M. and 9 A.M., after you have fasted for 12 hours.
 Operator gives a test load of glucose, usually 75 – 100 gram
dextrose / 300 ml water, lemon flavored . Drink the entire solution
in 5 minutes.
 Blood samples are collected at 60 min., 90 min.,120 min. and
sometimes immediately after drinking oral glucose solution.
 Dose of Oral Glucose:
Dextrose :1 – 1.75 g/kg. body wt. (for adults0 and not exceeds 100
g. It is to be dissolved in 250 – 300 ml lemon flavored water.
 Samples
Blood samples ; fasting(basal) sample, after oral glucose load,
60min, 90min,120min. (in extended OGTT another 2 samples will
be taken at 2½hour and 3 hours). most important 1hr, 2hr. 3hr
CHS
Types of curves- OGTT

1. normal curve
2. diabetic curve
3. precipitated curve
4. flat curve
5. renal glycosuria curve

Normal curve values

Sample fasting (0 min) 60 min 90 min 120 min Unit

whole blood 5.6 8.9 7.8 6.1 mmol/L

(venous)
whole blood - 10.0 - 6.7 mmol/L
(capillary)
plasma / 6.4 10.3 9.0 7.8 mmol/L
serum
CHS
1= Normal (If the same but sugar in urine then sugar glucosuria)
2= Insulinoma --- Malabsorption --- Hypothyroidism
4= Hyperthyroidism
Between 4 and 5= Growth hormone (Acromegaly)-----Emotional (Pheochromocytoma) "Epinephrin"
5= Hormonal disorders (Hypercorticism)
6= Diabetic
CHS
 (Normal glucose tolerance is represented by curve 1 and overt
diabetes by curve 6.)
 Hypercorticism increases the rate of intestinal glucose absorption to
produce an early and elevated postprandial peak serum glucose
concentration Glucose tolerance results are typified by curve 5.
 Acromegaly - Increased growth hormone stimulates glycogenolysis.
Glucose tolerance results are typically between curves 4 and 5.
 Hyperthyroidism increases the rate of intestinal glucose absorption
to produce an early and elevated peak postprandial serum glucose
concentration. Typical glucose tolerance results are represented by
curve 4.
 Pheochromacytoma (or "emotional hyperglycemia") - Increased
epinephrine increases glycogenolysis resulting in increased fasting
and postprandial serum glucose concentrations. Glucose tolerance
results are typically between curves 4 and 5. Epinephrin
 Pathologic conditions causing flat or depressed glucose
CHS
tolerance results
 Insulinoma causes rapid uptake of glucose by
peripheral tissue resulting in fasting hypoglycemia
.Curve 2
 Intestinal malabsorption results in a minimal
increase in postprandial serum glucose
concentrations. Curve 2
 Hypothyroidism causes a reduced rate of intestinal
absorption of glucose and depressed glucose
tolerance results typified by curve 2.
 Types of curves-OGTT
CHS
 Diabetic curve: The maximal concentration is abnormally high,
while fasting glucose levels need not always be elevated. If the
maximal glucose concentration exceeds renal threshold, then
glucosuria is also present.
Precipitated curve ( Lag storage curve): in some patients, the
maximal concentration of glucose is achieved already at 30
minutes, to decline to normal or even lower after 2 hours. This
curve type is observed in patients with reactive hypoglycemia,
after gastrectomy or gastrojejunostomy, in severe liver diseases
(reduced glycogenesis), etc.
Flat curve: glucose load results in only a slight increase in blood
glucose concentration. This curve type is observed in patients
with glucocorticoid or growth hormone deficiency, however, it
may quite frequently be found in healthy individuals.
Renal glycosuria curve: OGTT is completely normal, however,
glucosuria is found in some or even all urine samples
CHS

KNOW THEM FOR EXAM

CHS Diagnosis of Pre-diabetes and Diabetes
Test Fasting Plasma Glucose Oral Glucose Tolerance Test Random/Casual
(FPG) (OGTT Plasma Glucose
(with symptoms)
How Bd glucose is measured 75 gm glucose load (drink) is Blood glucose is
performed after at least an 8 hr fast ingested after at least an 8hr measured at any
fast time regardless
Blood glucose is measured at of eating
2 hrs
Normal < 100mg/dl (5.6 mmol/L) < 140 mg/dl (7.8 mmol/L)

Pre- 100-125 mg/dl

diabetes (5.6-6.9 mmol/L)
IFG

Pre- 140-199 mmol/dl

diabetes (7.8-11 mmol/L)
IGT

Diabetes ≥ 126 mg/dl (7 mmol/L) ≥ 200mg/dl (11.1 mmol/L) ≥ 200mg/dl

Mellitus (11.1 mmol/L)
111
(with symptoms)
Metabolism of Monosaccharides
and Disaccharides

MLS 218
OVERVIEW
 Glucose is the most common
monosaccharide consumed by humans, and
its metabolism has been discussed
extensively.
 However, two other monosaccharides—
fructose and galactose—occur in significant
amounts in the diet, and make important
contributions to energy metabolism.
 In addition, galactose is an important
component of cell structural carbohydrates.
 FRUCTOSE METABOLISM

 The major source of fructose is the

disaccharide sucrose, which, when cleaved
in the intestine, releases equimolar amounts
of fructose and glucose.

 Fructose is also found as a free

monosaccharide in many fruits, in honey, and
in high-fructose corn syrup which is used to
sweeten soft drinks and many foods.

 Fructose does not promote the secretion of

insulin.Natural sugars are better "Fructose" bec it does not increase glucose level. It enters glycolysis in stage 2 and disappears
from blood rapidly as the rate of metabolism is faster and that is why no insulin secretion
 PHOSPHORYLATION OF FRUCTOSE
 For fructose to enter the pathways of
intermediary metabolism, it must first be
phosphorylated

 Hexokinase phosphorylates glucose in all cells

of the body, and several additional hexoses can
serve as substrates for this enzyme. However, it
has a low affinity for fructose.

 Hence , Fructokinase provides the primary

mechanism for fructose phosphorylation

 It is found in the liver (which processes most of

the dietary fructose), kidney, and the small
intestinal mucosa, and converts fructose to
fructose 1-phosphate, using ATP as the
phosphate donor.
 CLEAVAGE OF FRUCTOSE 1-PHOSPHATE
 Fructose 1 -phosphate is cleaved by
aldolase B (also called fructose 1-phosphate
aldolase) to dihydroxy-acetone phosphate
(DHAP) and glyceraldehyde.

 DHAP can directly enter glycolysis or

gluconeogenesis, whereas glyceraldehyde
can be metabolized by a number of
pathways,

 The rate of fructose metabolism is more rapid

than that of glucose because the trioses
formed from fructose 1 -phosphate by pass
phosphofructokinase—the major rate-limiting
step in glycolysis.-This explains why
fructose disappears from blood more
rapidly than glucose
 2 fates:
enters into glycolysis
can also lead to formation of glucose

enters into glycolysis

Form glucose in (INDIRECT) formation of glucose (INDIRECT)
Direct pathway for fructose breaks down
(More convenient) bec both are glycolysis
intermediate as the enzyme is always there
the 2nd stage of glycolysis starts here

Trios isomerase
 DISORDERS OF FRUCTOSE METABOLISM
 Fructokinase deficiency-Essential fructosuria
✓ A deficiency of one of the key enzymes required for the entry of
fructose into intermediary metabolic pathways can result in this
benign condition
 Aldolase B deficiency (hereditary fructose intolerance, HFI),
✓ The first symptoms of HFI appear when a baby is weaned and begins
to be fed food containing sucrose or fructose.
✓ Fructose 1-phosphate accumulates, resulting in a drop in the level
of inorganic phosphate (Pi) and, therefore, of ATP.
✓ ATP falls, AMP rises. In the absence of Pi, AMP is degraded, causing
hyperuricemia. When conducting tests:
low inorganic phosphate which means low ATP
High uric acid

✓ The decreased availability of hepatic ATP inhibits gluconeogenesis

(causing hypoglycemia with vomiting), and protein synthesis
(causing a decrease in blood clotting factors and other essential
proteins).
✓ Diagnosis of HFI can be made on the basis of fructose in the urine.
In HFI, sucrose as well as fructose, must be removed from the diet to
prevent liver failure and possible death.
normally= normal amount of uric acid
MANNOSE METABOLISM
 Conversion of mannose to fructose 6-
phosphate
✓ Mannose, is an important component of
glycoproteins.
✓ Hexokinase phosphorylates mannose,
producing mannose 6-phosphate, which, in
turn, is (reversibly) isomerized to fructose
6-phosphate by phosphomannose
isomerase.
✓ There is little mannose in dietary
carbohydrates.
✓ Most intracellular mannose is synthesized
from fructose,
✓ Also exists as preexisting mannose produced
by the degradation of structural carbohydrates
Hexokinase Phosphomannose isomerase
Mannose Mannose-6-phosphate Fructose-6-phosphate
SYNTHESIS OF SORBITOL
Significance of Conversion of glucose to
fructose via sorbitol in seminal vesicles and
liver
• Aldose reductase reduces glucose, producing
sorbitol
Glucose Aldose reductase Sorbitol

• In cells of the liver, ovaries, sperm, and seminal

vesicles, there is a second enzyme, sorbitol
dehydrogenase, that can oxidize the sorbitol to
produce fructose
Sorbitol dehydrogenase
Sorbitol (Oxidized) Fructose

• The two-reaction pathway from glucose to

The pathway from sorbitol to
fructose in the seminal vesicles is for the benefit fructose in the liver provides a
mechanism by which any
available sorbitol is converted into
of sperm cells, which use fructose as a major a substrate that can enter
glycolysis or gluconeogenesis.
carbohydrate energy source.
 The effect of hyperglycemia on sorbitol metabolism:

 Elevated intracellular glucose

concentrations and a adequate supply
of NADPH cause aldose reductase to
produce a significant increase in the
amount of sorbitol,

 When sorbitol dehydrogenase is low

or absent, for example, in retina, lens,
kidney, and nerve cells sorbitol
accumulates in these cells
excess glucose = excess sorbitol because even if the enzyme is there, it can't convert all sorbitol to
fructose. Sorbitol accumulates in the body (liver, eyes, kidneys....)

 Leading to cataract formation,

peripheral neuropathy, and vascular
problems leading to nephropathy and
retinopathy.
know the difference between
the two reactions
GALACTOSE METABOLISM_
A. Phosphorylation of galactose
Like fructose, galactose must be
phosphorylated before it can be further
metabolized. Most tissues have a specific
enzyme for this purpose, galactokinase,
which produces galactose 1-phosphate
galactokinase galactose 1-phosphate uridyltransferase
Galactose Galactose-1-phosphate UDP-galactose

B. Formation of UDP- galactose

Galactose 1-phosphate cannot enter the
glycolytic pathway unless it is first
converted to UDP-galactose .
The enzyme that catalyzes this reaction
is galactose 1-phosphate
uridyltransferase.
 Use of UDP- galactose as a carbon source
for glycolysis or gluconeogenesis
 For UDP- galactose to enter the mainstream
of glucose metabolism, it must first be
converted to UDP-glucose,
 This "new" UDP-glucose (produced from the
original UDP-galactose) can then participate
in many biosynthetic reactions,
Role of UDP-galactose in biosynthetic
reactions
 UDP-galactose can serve as the donor of
galactose units in a number of synthetic
pathways, including synthesis of lactose (see
below), glycoproteins, glycolipids, and gly-
cosaminoglycans.
for synthesis of complex carbohydrates

glycolysis "Energy generation"

 Disorders of galactose metabolism

Gatactose 1 -phosphate Uridyltransferase is

missing in individuals with classic
GALACTOSEMIA
 In this disorder, galactose 1 -phosphate and,
therefore, galactose accumulate in cells.

 The accumulated galactose leads to galactitol

production. This reaction is catalyzed by
aldose reductase, the same enzyme that
converts glucose to sorbitol. Can lead to
cataract formation
Aldose reductase
Galactose-1-phosphate Galactitol
 LACTOSE SYNTHESIS
 Lactose is a disaccharide that consists of a
molecule galactose attached by a β(1-»4)
linkage to glucose.
 Lactose, known as the "milk sugar,"

 Lactose is synthesized in the Golgi by

lactose synthase (UDP-galactose:glucose
galactosyltransferase),

 This enzyme is composed of two

proteins, A and B.

 Protein A is a β-D-gatactosyl
transferase, and is found in a number of
body tissues. In tissues other than the
lactating mammary gland, this enzyme
produces N-acetyl lactosamine— a N-
linked-glycoprotein. function not related to milk in other tissues
 Cont…
Protein B is found only in lactating
mammary glands. It is a-lactalbumin, and
its synthesis is stimulated by the peptide
hormone, prolactin.
Protein B forms a complex with the
enzyme, protein A, changing the
specificity of that transferase so that
lactose, rather than N-acetyl lactosamine,
is produced both proteins together
produce lactose
Pentose Phosphate Pathway
( HMP)
MLS 218
Objectives
 To understand the function of the
pentose phosphate pathway In production
of NADPH and precursors for nucleic
acid synthesis.
Introduction 4th option for glucose-6-phosphate to convert

 In most animal tissues, glucose is catabolized via

the glycolytic pathway into two molecules of
pyruvate. Pyruvate is then oxidized via the citric
acid cycle to generate ATP.
 There is another metabolic fate for glucose
used to generate NADPH and specialized
products needed by the cell. This pathway is
called the pentose phosphate pathway also
called as the hexose monophosphate shunt
(HMP shunt), or the phosphogluconate
pathway.
Cont..
 The pentose phosphate pathway produces NADPH
which is the universal reductant in anabolic pathways.
 In mammals the tissues requiring large amounts of
NADPH produced by this pathway are the tissues that
synthesize fatty acids and steroids such as the
mammary glands, adipose tissue, adrenal cortex and the
liver.
 Tissues less active in fatty acid synthesis such as
skeletal muscle are virtually lacking the pentose
phosphate pathway.

 The second function of the pentose phosphate

pathway is to generate pentoses, particularly ribose
which is necessary for the synthesis of nucleic acids.
Cont…
 The pentose phosphate pathway has
two distinct phases:
 the oxidative phase , which produces
NADPH and the pentose ribulose-5-
phosphate ; for biosynthetic pathways or nucleic acid synthesis

 the rearrangement phase ( non

oxidative phase ), which rearranges
pentose phosphates into Triose and
hexose phosphates , which can be returned
to the normal glycolysis sequence
should reconnect to glycolysis
Summary of HMP pathway
know them

glycolytic intermediates are formed

Regulation

 The first reaction is the irreversible and is the

committed step
 This reaction is catalyzed by glucose -6 –
phosphate dehydrogenase and is allosterically
regulated
 This enzyme is inhibited at high concentrations of
NADPH
G6PD deficiency
 Mutations present in some populations causes a deficiency in
glucose 6 ‐ phosphate dehydrogenase, with consequent
impairment of NADPH production.

 Reduced glutathione (GSH) protects the cell by destroying

hydrogen peroxide and hydroxyl free radicals. Regeneration of
GSH from its oxidized form (GS‐SG) requires the NADPH
no NADPH = No reduced glutathione
 Detoxification Of H2O2 is inhibited, and cellular damage results
‐ leads to erythrocyte membrane breakdown and hemolytic
anemia.
benign and asymptomatic
 Most G6PD ‐ deficient individuals are asymptomatic ‐ only in
combination with certain environmental factors (sulfa antibiotics,
herbicides, antimalarials, *divicine)do clinical Manifestations
occur.
 College of Health Sciences
CHS

Metabolism of Lipid
MLS 218
 Objectives
CHS
1. To understand Lipid digestion and absorption.
2. To describe the mechanism of glycerol and fat oxidation.
3. Explain synthesis of phosphatidic acid and list different membrane
phospholipids
4. To become familiar with the amount of energy produced during the
oxidation of fat.
5. To describe process of digestion, absorption and synthesis of lipids
6. Describe the types and role of lipoproteins
7. Explain ketogenesis and ketosis
8. Explain cholesterol metabolism and its role in atherosclerosis
9. Desribe fatty liver and lipotropic factor
10.Explain the effects of hormones on lipid metabolism
11. Explain different types of hyperlipoproteinemia
12.Interpret the cases of various metabolic disorders
CHS
Metabolic Interrelationship

lipolysis

synthesis of lipids needs Acetyl CoA

breakdown gives Acetyl CoA
CHS Digestion of Triacylglyceroles
• Triacylglycerols (TAGs) pass through the mouth
unchanged and enter the stomach.
• The heat and churning action of the stomach break
lipids into smaller droplets.
• partially digested food leaves the stomach, it enters the
upper end of the small intestine (the duodenum).
• triggerring the release of pancreatic lipases, enzymes
for the hydrolysis of lipids.
• The gallbladder simultaneously releases bile.
• Bile contains bile acids and cholesterol. Cholic acid is
the major bile acid,which emulsify the lipid droplets so
they can be acted on by the pancreatic lipases.
TAG --- Stomach --- Heat and churning --- Small droplets --- duodenum
CHS
Digestion of Triacylglyceroles
• . Pancreatic lipase partially hydrolyzes the
emulsified triacylglycerols, producing mainly
mono- and diacylglycerols, plus fatty acids
and a small amount of glycerol
in the intestine
4 products free fatty acids

free glycerol
CHS cannot be transferred to the
Lipid absorption blood independently, it
needs proteins

Smaller fatty acids and glycerol are absorbed directly

through the surface of the villi that line the small intestine
and enter the bloodstream through capillaries.
The insoluble acylglycerols and larger fatty acids within
the intestine are packaged into the lipoproteins.
Chylomicrons "Lipoprotein" transports dietary lipids in intestine through blood to liver

by lipoprotein

directly

small bec less carbon

CHS Lipoprotein for lipid transport
• Lipids enter metabolism from three different sources:
– (1) the diet
– (2) storage in adipose tissue transported by different mechanism
– (3) synthesis in the liver
• Whatever their source, these lipids must eventually be
transported in blood.
• To become water-soluble, fatty acids released from
adipose tissue associate with albumin, a very large
protein that binds up to 10 fatty acid molecules.
• All other lipids are carried by lipoproteins of various
types.
CHS Lipoproteins
• contains a core of neutral
lipids, including
triacylglycerols and in the center "Core"

cholesteryl esters.
• Surrounding the core is a
layer of phospholipids in
which varying proportions
of proteins and cholesterol
are embedded.

intrinsic proteins= on the inside or half in half out

extrinsic= only on the surface

8
CHS
Lipoproteins
Tests done for liver profile:
total cholesterol
total glycerol
LDL
HDL
VLDL

Lipoprotein Density Diameter Protein % Phospholip Triacylglycero

class (g/mL) (nm) of dry wt id % l % of dry wt
HDL 1.063-1.21 5 – 15 33 29 8

LDL 1.019 – 1.063 18 – 28 25 21 24

IDL 1.006-1.019 25 - 50 18 22 31

VLDL 0.95 – 1.006 30 - 80 10 18 50

chylomicrons < 0.95 100 - 500 1-2 7 84

 Types of lipoproteins
CHS
• Chylomicrons, transport of lipids from the diet.
• Very-low-density lipoproteins (VLDLs) carry TAGs from the liver
to peripheral tissues for storage or energy generation
• Low-density lipoproteins (LDLs) transport cholesterol from the
liver to peripheral tissues, where it is used in cell membranes or for
steroid synthesis. LDL cholesterol can also cause formation of
arterial plaque (Bad cholesterol)

• High-density lipoproteins (HDLs) transport cholesterol from dead

or dying cells back to the liver, where it is converted to bile acids.
The bile acids are then available for use in digestion or are excreted
when in excess. HDL is also called good cholesterol ifliver,
cholesterol does not enter the
it stays in the blood
high LDL and low HDL is harmful causing blockage in arteries "
It should be normal amount of both heart diseases"

10
 Lipoprotein- general structure
CHS APO

APOLIPOPROTEIN
• major components of
lipoproteins often referred to
as apoproteins
• classified by alphabetical
designation (A-E) 5 classes
• the use of roman numeral
suffix describes the order in
which the apolipoprotein
emerge from a
chromatographic column
 Apoproteins
CHS
• A-I : principal protein in HDL
• activates LCAT(Lecithin-cholesterol acyltransferase) is an
enzyme that converts free cholesterol into cholesteryl ester
• A-II– occurs mainly in HDL
• enhances hepatic lipase activity
• B-48 – found only in chylomicron
– lacks the LDL receptor-binding domain of apo-B-100
• B-100– in LDL. binds to LDL receptor also in IDL but mainly LDL
• C-I – found in chylomicron, VLDL, HDL may also activate LCAT
• C-II - found in chylomicron, VLDL, HDL activates lipoprotein
lipase
• C-III - found in chylomicron, VLDL, IDL, HDL inhibits lipoprotein
lipase
• D - found in HDL also called cholesterol ester transfer protein
(CETP)
• E - found in chylomicron, VLDL, I DL
CHS

CM LDL VLDL HDL

－ ＋

Origin CM b Pre-b a
mainly
other names of the lipoproteins diseases
are relayed
to these

Separation of plasma lipoproteins by

electrophoresis on agarose gel
 Lipid Metabolism:Dietary fat is transported to the liver by
CHS chylomicrons

TG-rich
core

difference: Chylomicrons change

in blood as A and C are no longer
there, there for only the remanent
are there.
 Lipoprotein Metabolism :Hepatic lipids are secreted as VLDL
CHS and subsequently converted to LDL
pick cholesterol to the liver

same CE-rich
receptors

TG-rich cholesterol
secretion
HDL

HDL
CHS Lipoprotein Metabolism
cholesterol from the
tissues to the liver to be
stored

Liver does not recognize the normal

chylomicrons that is why it is
converted to remanent
 dietary lipids by chylomicrons
lipids from Exogenous Pathway Endogenous Pathway
lipids synthesized in the body
outside
CHS
(Diet) Bile acids and
Dietary fat Cholesterol LDL
LDL-R

Liver Endogenous
Cholesterol LDL-R
Extra Hepatic
Intestine Dietary
Cholesterol Tissue
Remnant
Receptor

Chylomicrons Remnants VLDL IDL HDL

Lipoprotein lipase Lipoprotein lipase

Free fatty acids Free fatty acids

Adipose tissue, muscle Adipose tissue, muscle

 Lipid Metabolism-Overview end product is
2 molecules of
CHS lipolysis and lipogenesis Acetyl-CoA

fatty acid with breakdown in mitochondria

many (B-oxidation) and fatty acid is
carbons (eg: needed thus it should be maximum a fatty
16) transferred from cytosol to acid with 16
carbons ONLY
mitochondria before with this process
B-oxidation starting
4 End product of B-oxidation is
reactions Acetyl-CoA and it is required
in each for the synthesis of fatty acid increase by 2 C
and a donor will
B-oxidatio give 2 carbons
each time
n Synthesis in cytosol
TOTAL: 7 (Lipogenesis) and Acetyl-CoA
CYCLES needs to be transported from
and 8 mitochondria to cytosol
AcetylCoA
enzymes are only breaking
down the fatty acids in the
body (in the mitochondria)
requires activated fatty acids
Shortened
that can be then converted to
by 2C (Eg:
Acetyl-CoA
14)

the other 2 carbons are here

Eg: Total 16C fatty acid
7 cycles and 8 AcetylCoA
12x8= 96ATP A question about this will come
Additionally, 7NADH and 7FADH2 (If written then show all the steps)
7 NADH= 21
7 FADH2= 14
= 35 -2 (Used at the beginning for activation)

129 TOTAL
 Breakdown of Triacylglycerols
CHS
Triacylglycerols undergo hydrolysis to
fatty acids and glycerol.
Fate of Fatty acids
Resynthesis of triacylglycerols for
storage can be used for energy or to synthesis other fatty acid
Conversion to acetyl-SCoA
Fate of Glycerol
glyceraldehyde 3-phosphate and
DHAP, which participate in
Glycolysis—energy generation
Gluconeogenesis—glucose formation
Triacylglycerol synthesis
The lipases break the triacylglycerols down to fatty acids
and glycerol
19
The fatty acids are transported in the blood by serum
albumin
CHS

ATP Utilizing reaction

CHS

glycolysis reaction

ENTERS THE SECOND PHASE OF

GLYCOLYSIS FORMING PYRUVATE
CHS

gives 3ATP

2nd phase of glycolysis

one is used in the first reaction (Glycerol to glycerol-3-phosphate)

CHS Phospholipids
▪Polar compounds composed of alcohol attached to either
diacylglycerol or sphingosine.

▪ Amphipathic in nature, has a hydrophilic head (phosphate +

alcohol eg., serine, ethanolamine, and choline) and a long,
hydrophobic tail (fatty acids or derivatives ).

▪ In membranes, the hydrophobic portion is associated with the

nonpolar portions such as glycolipids, proteins, and cholesterol.

▪ The hydrohilic polar head extends outward, facing intracellular

or extracellular aqueous environment
CHS
CHS
CHS
CHS
Phosphatidic acid synthesis
CHS
Fatty acid metabolism

28 Chapter Twenty Five Prentice Hall © 2007

CHS
Oxidation of fatty acids
• Also called as β-oxidation
• occurs in mitochondria of liver
• Two carbons are successively removed in the
form of acetyl CoA
• Breakdown of fatty acids involves 3 processes
1. Activation
2. Transport of fatty acid fronm cytosol to
mitochondria
3. Oxidation
CHS
Fatty Acid Activation
Fatty acid activation- takes place in the cytoplasm
• fatty acid combines with CoA to yield fatty acyl CoA
• Acyl CoA is activated fatty acid ( breaks down easily)
• Carnitine carries long-chain activated fatty acids into
the mitochondrial matrix

AcylCoA
appears like 1
not Acetyl ATP but it is 2
30 ATPs used
M=mono + 2P
CHS Fatty Acid Transport
• the fatty acyl group combines with carnitine
• the fatty acyl molecule moves across the inner
membrane into the mitochondrial matrix for
oxidation

31 cross mitochondrial membrane

 Summary of Fatty Acid Activation
CHS

◼ Fatty acid activation is complex, but it regulates the

degradation and synthesis of fatty acids.

intermembrane but
cannot pass the inter
inner membrane membrane

it will go out to to get inside

be used again

32
CHS β-Oxidation
that is why called B-oxidation
CHS β-Oxidation
In reaction 1, oxidation In reaction 3, a second
• removes H atoms from the oxidation
a and b carbons • forms a keto group on the b
• reduces FAD to FADH2 carbon
• reduces NAD+ to NADH +
H+
In reaction 2 , hydration In reaction 4, Cleavage
• adds water • forms shortened fatty acyl
• forms a hydroxyl group CoA that repeats steps 1–4
(—OH) on the b carbon of b oxidation
CHS Equation for One Cycle of b Oxidation

one

2 AcetylCoA only on the last cycle of B-oxidation

35
 Fatty Acid Length and b Oxidation
CHS

The length of a fatty acid

• determines the number of b-oxidation cycles
• determines the total number of acetyl CoA groups

36
CHS
ATP and b Oxidation
Activation of a fatty acid requires 2 ATP.

One cycle of oxidation of a fatty acid produces

1 NADH 3 ATP
1 FADH2 2 ATP

Acetyl CoA entering the citric acid cycle produces

1 Acetyl CoA 12 ATP

37
CHS
ATP for Lauric Acid C12

ATP production for lauric acid (12 carbons):

Activation of lauric acid −2 ATP
6 Acetyl CoA:
6 Acetyl CoA x 12 ATP/acetyl CoA 72 ATP
5 Oxidation cycles:
5 NADH x 3ATP/NADH 15 ATP
5 FADH2 x 2ATP/FADH2 10 ATP
Total 95 ATP

38
CHS
Learning Check
The total ATP produced from the b oxidation of
stearic acid (C18) is:
18/2 = 9 AcetylCoA
9-1 = 8 Cycles
12 x 9= 108ATP
1) 108 ATP 8 Cycles:
8 NADH = 24

2) 146 ATP 8 FADH2 = 16

TOTAL= 148 - 2 = 146

3) 148 ATP

39
CHS
Solution
The total ATP produced from the b
oxidation of stearic acid (C18) is:
2) 146 ATP

40
 Ketone Bodies
When person is facing diabetic ketoacidosis OR after breakdown
in diabetes it is dangerous
because already there is
glucose for the brain so it
might be fatal
CHS
If carbohydrates are not
available,
• body fat breaks down to meet reversible so go to TCA
cycle in brain

energy needs inbodies,

keto diet, if there is a lot of ketones
then the brain might not need this
much. The blood becomes acidic

• oxaloacetate in liver is depleted

due to gluconeogenesis.
• This impedes acetyl-CoA entry
to Krebs cycle. Acetyl-CoA in greens are
ketones bodies
liver mitochondria is converted
then to ketone bodies.
Ketone bodies are also produced
When there is too much acetyl-
41 you can smell
CoA for the citric acid cycle to it in people's
mouth
CHS
Ketogenesis
In ketogenesis,
• large amounts of acetyl CoA accumulate
• two acetyl CoA molecules combine to form
acetoacetyl CoA
• acetoacetyl CoA hydrolyzes to acetoacetate, a
ketone body
• Acetoacetate reduces to b-hydroxybutyrate or
loses CO2 to form acetone, both ketone bodies
• Ketosis occurs in diabetes, diets high in fat, and
starvation
42
 Ketone Bodies and Energy
CHS

• The ketone bodies can travel unassisted in the

bloodstream to tissues where acetyl-CoA is
produced from acetoacetate and β-
hydroxybutyrate.

• In this way, acetyl-CoA is made available for energy

generation when glucose is in short supply.

• Ketone bodies are a major source of energy for

brain during starvation.
can cross the brain barriers

43
 Ketosis
CHS

• Is the condition in which ketone bodies are produced

faster than they are utilized
• occurs in diabetes
It is indicated by
• accumulation of ketone bodies in blood and urine.
• Ketonemia, excess accumulation of ketone bodies in
blood.
• Ketonuria, excess accumulation of ketone bodies in urine.
• Ketosis is also indicated by the odor of acetone on the
patient’s breath
 Ketoacidosis
CHS

• results from increased concentrations of ketone

bodies in the blood.
• blood pH drops.
• causes dehydration due to increased urine flow.
• causes labored breathing because acidic blood is a
poor oxygen carrier,
• causes depression
• and ultimately, if untreated, the condition leads to
coma and death
 Link between Lipd metabolism an other metabolic
CHS pathways
• Since lipogenesis is the the biosynthesis of fatty acids
from acetyl-CoA,it provides a link between
carbohydrate, lipid, and protein metabolism.
• Acetyl-CoA is an end product of carbohydrate and amino
acid catabolism, using it to make fatty acids allows the
body to divert the energy of excess carbohydrates and
amino acids into storage as TAGs.
• Protein metabolism contribute intermediates for
phospholipids
• Carbohydrates can be synthesiszed from glycerol
 Lipogenesis: Fatty Acid Synthesis
CHS

Fatty acid are synthesized and degraded by different pathways

– Synthesis takes place in the cytosol.
– Intermediates are attached to the acyl carrier protein (ACP).
– The activated donor in the synthesis is malonyl–ACP.
needs a donor to add 2C every time

– Fatty acid synthesis uses NADPH + H+.

– Elongation stops at C16 (palmitic acid)

47
 Citrate Shuttle
CHS

Acetyl–CoA is synthesized in the mitochondrial matrix,

whereas fatty acids are synthesized in the cytosol

– Acetyl–CoA units are shuttled out of the mitochondrial matrix as

citrate
goes back

reaction ONLY in the cytosol

48
 Lipogenesis
CHS
• Needs two initial reactions:
– (1) transfer of an acetyl group from acetyl-CoA to an acyl
carrier protein (ACP)
– (2) conversion of acetyl- CoA to malonyl-CoA

The malonyl-CoA is then transferred to the acyl carrier protein

(ACP) to form Malonyl-ACP

AcetylCoA

AcetylCoA

49
 2C
CHS
Lipogenesis
The result of the
first cycle in fatty
acid synthesis is the
addition of 2 C
atoms to an acetyl
group to give a 4-
carbon acyl group.

50 4C
Then the cycle repeats until we get 16C
fatty acid
CHS Lipogenesis
• After seven trips through the elongation, a 16-carbon
palmitoyl group is produced. Larger fatty acids are
synthesized from palmitoyl-SCoA with the aid of
specific enzymes.

51
CHS
Lipogenesis: Fatty Acid Synthesis
no double bond

• Increases on high
2 reactions "Saturated"
-Desaturation: Adds double bond
-Elongation: large fatty acids
carbohydrate diet.
• decreases on high fat diet or 16 is carbons. 1 is the
double bond. 9 is the
position of the double
bond (Between 9 and 10)

deficiency of insulin. (diabetes)

• Palmitate can then be modified
to give other fatty acids by:
• Chain elongation to give
longer fatty acids, such as the
18-carbon. (Stearate)
• Desaturation, giving
unsaturated fatty acids.
 Stoichiometry of FA synthesis
CHS

1. Synthesis of Malonyl–CoA from Acetyl–CoA

2. Synythesis of palmitate from Malonyl–CoA

3. Overall synthesis

53
CHS
Regulation of Fatty Acid Synthesis
• a high level of blood glucose and insulin
stimulates glycolysis and pyruvate oxidation
• more acetyl CoA is available to form fatty
acids

GLUCOSE ACETYL COA FATTY ACID

54
CHS
b Oxidation and Fatty Acid Synthesis

55
CHS
Hormonal Control
Insulin
a. Increased fatty acid synthesis
b. Decreased mobilization of stored fats
c. Decreased gluconeogenesis
d. decreased ketogenesis

Glucagon
a. Decreased fatty acid synthesis
b. Increased mobilization of stored fats
c. Increased gluconeogenesis
d. Increased oxidation
CHS Other hormones
a. ACTH Increases ketogenesis
b. Glucocorticoids in the absence of insulin
leads to ketogenesis
c. Epinephrine in the presence of adrenocortical
hormones stimulates ketogenesis
d. Thyroxine decreases plasma cholesterol
e. Thyroxine therapy in conjunction with
inadequate insulin a can cause ketogenesis
 Obesity "Disorder"
CHS no balance between intake and utilization
• Obesity is a medical condition in which excess body fat
accumulates
• Body mass index (BMI), defines people as overweight (pre-
obese) if their BMI is between 25 and 30 kg/m2, and obese
when it is greater than 30 kg/m2
• caused by a combination of excessive food energy intake,
lack of physical activity, and endocrine disorders etc.
• increases the likelihood of various diseases, particularly
heart disease, type 2 diabetes and hypertension stroke, kidney
problems
 Obesity
CHS

Food

adipose tissue
adipose
tissue
fatty acids &
triacyl- Obesity
glcerols
Work
or ADP
Growth

ATP

Heat
CO2 + H2O
CHS
Structure and function of cholesterol
1. Function of cholesterol: needed but not in very high level

(1) It is a constituent of all cell membranes.

(2) It is necessary for the synthesis of all steroid hormones, bile salts
and vitamin D.
All steroids have cyclopentano penhydro phenanthrene ring system
Cholesterol molecule:
- 4 Rings
- 27 carbon atoms H3C 21 23 25 CH3
- 5 CH3 groups (Methyl groups) "18, 19, 21, 26, 27 " 22 24 26
- One double bond (Between carbons 5 and 6) in ring B 20
- 1 OH (At carbon 3) in ring A 18 CH 3
27 CH 3
12 17
11 13 D 16
19 CH 3 C
14 15
1 9
2 10 8
A B
3 5 7
4 6
HO
 Synthesis of cholesterol
CHS
Location:
• All tissue except brain and mature red blood cells.
• The major organ is liver (80%).
• Enzymes located in cytosol and endoplasmic reticulum.
Materials:
Acetyl CoA, NADPH(H+), ATP
CHS Synthesis of Cholesterol
Stage I: three acetyl-CoA molecules condense to
form the 6-carbon mevalonate
Stage II: mevalonate is converted to activated 5-
carbon isoprene
Stage III: Six isoprene units condense to form
the linear 30-carbon squalene
Stage IV: The linear squalene is cyclized to
form a four-ring structure, which is eventually
converted to the 27-carbon cholesterol through a
series of complicated reactions.
CHS
Biosynthesis of Cholesterol

1.Formation of
mevalonate
2.Conversion to
activated isoprene
3.Polymerization of
isoprene
4.Cyclization of
squalene
CHS
Regulation of Cholesterol Synthesis
STATINS= lipid lowering drug
it inhibits the enzyme (HMG-CoA reductase) in the first stage. If inhibited then no cholesterol
One molecule of β-hydroxy-β-methylglutaryl-CoA
(HMG-CoA) is formed from three acetyl-CoA
molecules in the cytosol via the same reactions as
occurring in mitochondria for ketone body formation.
HMG-CoA reductase (an integrated membrane
protein in the smooth ER) catalyzes the irreversible
reduction of HMG-CoA (using two molecules of
NADPH) to form mevalonate: committing the
acetyl groups for cholesterol synthesis (thus being a
major regulation step).
CHS

a substrate for the enzyme

below

The irreversible committing step for cholesterol

biosynthesis
CHS

Regulation of cholesterol synthesis

Glucagon negative feedback inhibiting the enzyme

fasting

HMG CoA reductase

HMG CoA MVA cholesterol
also help in
removal of
cholesterol
after meal insulin thyroxine
bile acid

the only way

CHS
Bile acids
Bile acids are amphipathic, with detergent
properties.
• Emulsify fat and aid digestion of fats & fat-
soluble vitamins in the intestine.
• Conversion to bile salts (sodium or potassium
salts of bile acids), is the only mechanism by
which cholesterol is excreted.
• Bile salts break down fat globules, allowing
pancreatic lipases to hydrolyze the triacylglycerol
CHS Classification of Bile Acids

The primary bile acids: Are synthesized in the

liver from cholesterol.

The secondary bile acids: Primary bile acids in

the intestine are subjected to some further
changes by the activity of the intestinal bacteria
CHS Types of Bile Acids

Free bile
Classification Conjugated bile acids
acids

Glycocholic
Cholic acid Taurocholic acid
acid
Primary bile
acids Glycocheno-
Chenodeoxy- Taurocheno-
deoxycholic
cholic acid deoxycholic acid
acid
Deoxycholic Glycodeoxy- Taurodeoxy-
acid cholic acid cholic acid
Secondary
bile acids
Lithocholic Glycolitho- Taurolitho-cholic
acid cholic acid acid
CHS
Atherosclerosis deposition of cholesterol
due to plaque formation

• Is defined as the process in

which deposits of fatty substances,
cholesterol, cellular waste products,
calcium and other substances build up
in the inner lining of an artery.
• Plaques can grow large enough to
significantly reduce the blood's flow
through an artery. But most of the
damage occurs when they become
fragile and rupture. Plaques that
rupture cause blood clots to form that
can block blood flow or break off
and travel to another part of the
body. If either happens and blocks a
blood vessel that feeds the heart, it
70
causes a heart attack.
CHS
Cachexia
• Destructive processes characterized by skeletal muscle
wasting and harmful abnormalities in fat, CHO, and protein
metabolism in spite of adequate caloric and nutrient intake.
• Cachexia is not starvation; starvation may be part of
cachexia and cachexia may result from starvation but
they are different.
• Cachexia vs. Starvation
– Starvation: loss of body fat and preservation of muscle
mass
– Cachexia: equal loss of fat and muscle, a loss of adipose
tissue, and increased energy expenditure. Adipose tissue
cells (adipocytes) have been shown to release enzymes in
71 CHF, which induce skeletal muscle wasting and reduce
CHS
Cont..
Cahexia is associated with various serious
illnesses including:
Many types of cancer (particularly of the
pancreas, stomach, oesophagus, colon and
rectum).
HIV/AIDS.
Congestive heart failure.
Rheumatoid arthritis.
Tuberculosis, chronic obstructive pulmonary
disease (COPD), cystic fibrosis. lung diseases
Crohn's disease.
CHS
Disorders of lipid metabolism
• Can be subdivided into two major categories
1.Hyperlipoproteinemia
• Hypercholesterolemia
• Hypertriglyceridemia
• Combined hyperlipoproteinemia
2.Hyolipoproteinemia
• Hypobetalipoproteinemia
• Hypoalphalipoproteinemia
• Abetalipoproteimnemia

73
 Hypercholesterolemia
CHS

• Associated with high risk of premature CAD

• Genetic defect in the LDL receptor gene
resulting in either absent or defective LDL
receptor activity
• This increases LDL cholesterol by 2-3 folds
CHS
Hypertriglyceridemia
• Familial • Generally caused by
hypertriglyceridemia deficiency of
– Genetic Lipoprotein lipase
• Secondary (LPL) or LPL cofactor.
hypertriglyceridemia • LPL hydrolyzes
– Hormonal imbalances triglycerides in
chylomicrons and
– Imbalance between VLDL
synthesis and
clearance of VLDL
75
CHS Combined Hyperlipoproteinemia
• Presence of elevated levels of serum total
cholesterol and triglycerides
• Obesity and insulin resistance are common
• Genetic form of this condition
– Familial combined hyperlipoproteinemia
(FCH)
– Type III hyperlipoproteinemia
• an accumulation of cholesterol-rich VLDL
and chylomicron remnants as a result of
defective catabolism of those particles
76
 Actually only 5 types but type 2 having a and b

CHS
Fredrickson Classification
Type Elevated Associated clinical Serum Serum
particles disorders TC TG

I Chylomicrons ↔
Lipoprotein lipase deficiency, normal ↑↑
very high
apolipoprotein C-II
deficiency

IIa LDL Familial ↑↑ ↔

hypercholesterolemia,
polygenic
hypercholeterolemia,
nephrosis, hypothyroidism,
familial combined
hyperlipidemia

IIb LDL, VLDL Familial combined ↑↑ ↑

moderately high
hyperlipidemia
CHS
Fredrickson Classification
Type Elevated Associated clinical Serum Serum
particles disorders TC TG

III IDL Dysbetalipoproteinemia ↑ ↑

IV VLDL Familial ↔↑ ↑↑
could be normal
hypertriglyceridemia, familial or moderately
high (Normal
combined hyperlipidemia, but close to
sporadic high)

hypertriglyceridemia,
diabetes

V Chylomicrons, Diabetes ↑ ↑↑
VLDL
CHS Hypolipoproteinemia
• Hypobetalipoproteinemia • Abetalipoproteimnemia
✓low LDL an d VLDL ✓ Absence of β-lipoproteins
✓Normal HDL ✓ Lipid accumulates in
• Hypoalphalipoproteinemia intestinal cells
✓ decrease in circulating HDL
✓ Excessive deposition of
cholesterol esters in many
tissues
– An extreme form -
Tangier Disease

79
 asymptomatic at the beginning

CHS
Fatty liver
• Fat makes up greater than 10% of the liver by weight, then
the condition is classified as fatty liver disease (FLD).
• Two types of FLD are generally recognized.
Alcoholic fatty liver disease results from excessive alcohol
intake.
Non-alcoholic fatty liver disease
✓ there is a imbalance between lipogenic (fat producing) and
lipotrophic (decreasing the deposit of fat) factors;
✓ insulin resistance plays an important role
✓ can be caused by a wide variety of factors including fat
rich diets, metabolic syndromes, obesity etc.
CHS
Laboratory Abnormalities
2-4 fold increase in liver enzymes SGPT and
SGOT
SGOT:SGPT ratio less than 1
SGOT:SGPT ratio more than 1 if cirrhosis sets
in
TG high
Fasting and pp sugar high
ALP slightly high
CHS
Summarry
Nucleic Acid Metabolism And
Disorders

MLS 218
Objectives

 Explain digestion and extracellular hydrolysis

of nucleic acids
 Identify and differentiate between purine and
pyrimidine bases
 Differentiate between de novo and salvage
pathways
 Outline the metabolic pathways and their
interpretations for disorders related to nucleic
acid metabolism
Introduction
 Nucleic acids (NAs) ingested from food are
acted upon in the digestive tract ( small
intestines) by endonucleases,
phosphodiesterase and nucleoside
phosphorylase into oligonucleotides,
nucleotides, and even free bases.
 Carbohydrate digestion
Oral cavity, Polysaccharides Disaccharides
pharynx, Salivary amylase
esophagus
Smaller Maltose
polysaccharides Protein digestion
polynucleotides
Proteins
Stomach Pepsin
Small polypeptides Nucleic acid digestion Fat digestion
DNA, RNA Fat (triglycerides)
in the small intestine
Small
intestine Pancreatic amylases Pancreatic trypsin and Pancreatic
chymotrypsin nucleases
(enzymes Disaccharides
from Smaller
pancreas) polypeptides Nucleotides Pancreatic lipase

Pancreatic carboxypeptidase

Glycerol, fatty acids,

Small peptides monoglycerides

Nucleotidases
Dipeptidases, carboxy-
Small peptidase, and
Nucleosides
intestine Disaccharidases aminopeptidase
(enzymes Nucleosidases
from and
phosphatases
epithelium)
Nitrogenous bases,
end product is separation of
Monosaccharides Amino acids sugars, phosphates these
 Enzymes for breakdown of Nucleic Acids

❖ Nuclease, a pancreatic enzyme that cleaves nucleic acids belong to the class
of enzymes called hydrolases, are usually specific in action, ribonucleases
acting only upon ribonucleic acids (RNA) and deoxyribonucleases acting only
upon deoxyribonucleic acids (DNA).

❖ Nucleotidase is a hydrolytic enzyme that catalyzes the hydrolysis of a

nucleotide into a nucleoside and a phosphate

❖Nucleosidases are class of enzymes that catalyze the hydrolysis of

nucleosides.
different bec polynucleotides "Acts on the beginning= endo" "Acts on the end= exo"

❖ Endonuclease: any of a group of enzymes that degrade DNA or RNA

molecules by breaking linkages within the polynucleotide chains.

❖ Exonuclease: Any of a group of enzymes that catalyze the hydrolysis of

single nucleotides from the end of a DNA or RNA chain.
accumulation of uric acid due to abnormality in breakdown of nucleic acid cause joints disease
The Nucleic Acid Bases

DNA:
A -T
G-C

RNA:
A-U
G-C

C
H

Uracil
(U)

RNA
only
 ONLY KNOW NAMES NOT STRUCTURES
Pentoses Found in Nucleic Acids Numbering System of Purine & Pyrimidine Nucleosides

KNOW THE SOURCES

Eg: Carbon 6 source is CO2
Nitrogen at carbon 1 source is Aspartate ...
 Basic mechanisms to generate purines and pyrimidines
 The biosynthesis of purine and pyrimidine nucleotides takes place by de
novo synthetic pathways from small molecules and by salvage
pathways from preformed purine or pyrimidine bases or nucleosides.
 The pathways of de novo synthesis are the same in animals and
microorganisms. de novo synthesis of purine nucleotides refers to the
process that utilizes small molecules such as phosphoribose, amino acids,
CO2 etc. as raw materials to produce purine nucleotides.
 Nucleotide salvage pathways recover bases and nucleosides, from RNA
and DNA degradation or from exogenous sources, to convert them back
to nucleotides
 Salvage pathways are considerably more energy‐efficient than de
novo pathways
 Salvage pathways are integral to the cause or treatment of a number of
human diseases of purine or pyrimidine metabolism.
 Salvage pathway
 Salvage of purines is catalysed by adenine
phosphoribosyltransferase (APRT) and hypoxanthine
guanine phosphoribosyltransferase (HGPRT).
 Pyrimidine salvage is catalysed by thymidine kinase.
 Pyrimidine salvage is effective in the treatment of orotic
aciduria, a disorder of pyrimidine nucleotide synthesis.
 Deficiency of APRT leads to renal calculi.
 Deficiency of HGPRT is the cause of Lesch–Nyhan
disease.
 Synthesis of 5-Phosphoribosyl-1-Phosphate
( 1st reaction of purine biosynthesis

increase in activity leads to more purines

broken down increasing uric acid

PRPP Synthetase: is the enzyme that catalyzes the reaction of

ribose-5-phosphate and ATP to produce PRPP and AMP; a
regulatory enzyme in purine & pyrimidine biosynthesis; enhanced
activity of this enzyme results in an increase in purine
biosynthesis leading to “Gout”.
 PRPP synthetase defects
 Purine synthesis is critical to fetal development,
therefore defects in enzymes will result in a
nonviable fetus.
 PRPP synthetase defects are known and have severe
consequences.PRPP synthetase superactivity results
in increased PRPP, elevated levels of nucleotides,
and increased excretion of uric acid.
 PRPP deficiency results in convulsions, autistic
behavior, anemia, and severe mental retardation.
 Excessive PRPP activity causes gout (deposition of
uric acid crystals)
 Lesch Nyhan syndrome
Lesch-Nyhan Syndrome is characterized by the
deficiency of “hypoxanthine-guanine
phosphoribosyl transferase (HGPRT)”, leads to
accumulation of PRPP and uric acid, the condition is
know as “Hyperuricemia”.

Up to 20 times the uric acid in the urine than in normal

individuals. Uric acid crystals form in the urine

.Untreated condition results in death within the first year

due to kidney failure.
Uric acid does not form from the PRPP pathway, but de novo pathway becomes active and start
producing purine. Uric acid formed from degradation of purine
Treated with allopurinol, a competitive inhibitor of
xanthine oxidase

The upper end of the normal range of uric acid is children bite
360 µmol/L (6 mg/dL) for women and 400 µmol/L their fingers

(6.8 mg/dL) for men.

PRPP=Phosphoribosyl pyrophospate.
 Disorders of Purine Metabolism:

Disorder Defect Comments

Gout PRPP synthase/ Hyperuricemia
HGPRT

Lesch Nyhan lack of HGPRT Hyperuricemia

syndrome

SCID ADA High levels of dAMP

mostly congenital
Sources of the Individual Atoms in
Pyrimidine Ring

sources and numbering

Summary of the Difference between
CPS-I & CPS-II in pyrimidine
synthesis

difference in
enzyme,
substances required

ammonia
CO2
Amino acid "Glutamine"

+ PRPP
De novo Pyrimidine Synthesis

know the causes of the disorder only

Synthesis of dTMP from dUMP, Ilustrating
Sites of Action of Antineoplastic Drugs
the cycle is happening with
the reaction and with cancer
cells they accelerate and
inhibits conversion of dUMP to dTMP thus inhibited with the drugs

5-Fluorouracil: An antineoplastic agent, used

especially in the treatment of cancers of the skin,
breast, and digestive system. Acts as inhibitor of
thymidylate syhthase

Methotrexate: inhibits conversion of dihydrofolate to

tetrhydrofolate leading to inhibition of dTMP
synthesis and is used in the treatment of psoriasis,
certain cancers, and certain inflammatory diseases,
such as rheumatoid arthritis.
 Orotic Aciduria

❖ Orotic aciduria refers to an excessive

excretion of Orotic acid in urine.

❖ Its hereditary form, an autosomal recessive

disorder, can be caused by a deficiency in the
enzyme Uridine monophosphate
synthetase (UMPS), a bifunctional protein
that includes the enzyme activities of Oroate
phosphoribosyltransferase and Orotidine
5’-phosphate decarboylase.
 Pyrimidine Degradation
❖ Pyrimidines are generally degraded to intermediates of carbon metabolism (for
example, succinyl-CoA) and ammonia (NH4+).

❖ NH4+ is packaged as urea through

the urea cycle and excreted by humans.

❖ Dihydropyrimidine dehydrogenase (DHPD) is responsible for the catabolism of the end-

products of pyrimidine metabolism (uracil and thymine) to dihydrouracil and
dihydrothymine

❖ A deficiency of DHPD leads to accumulation of uracil and thymine.

accumulation of pyrimidine bases

❖ Dihydropyrimidine amidohydrolase (DHPA) catalyses the next step in the further

catabolism of dihydrouracil and dihydrothymine to amino acids. A deficiency of DHPA
results in the accumulation of small amounts of uracil and thymine .
 218

Protein
Metabolism
Objectives
 Explain digestion of proteins
 Explain nitrogen balance
 Differentiate and explain essential, non essential,
glucogenic and ketogenic amino acids
 Comment on the role of transamination and oxidative
deamination
 Explain ammonia intoxication or hyperammonemia
 Explain synthesis of urea and disorders of urea cycle
enzymes
 List the plasma protein and their functions
 Comment on the role of hormones on protein
metabolism
 List and identify the clinically significant NPN
compounds
 proteins are the last source of energy

In protein metabolism,
ammonia is secreted outside
the body through urine (It major source of nitrogen in the
body
passed through blood).
Ammonia is converted to urea
to be secreted. Urea is
nontoxic.

stored in the body

after they are broken down nitrogen containing compounds

provide energy
form intermediate of TCA cycle and pyruvate
Precursors for ketone bodies

the structure of the amino acid with

the amino group being replaced

if the cytoskeleton is giving intermediate for the

TCA cycle then called glucogenic amino acid

If gives precursor for ketone bodies, then

called ketogenic amino acid

That gives both is called is called ketogenic

and glucogenic
 Types of nitrogen balance
Nitrogen equilibrium : Intake = excretion In healthy individuals

 Positive N balance  Negative N balance

 Intake> excretion  Intake < excretion
 During infancy ,  Inadequate calorie and
childhood, adolescence protein intake
normal situations
 Pregnancy  starvation , infection , abnormal situations

prolonged immobility
 Lactation
and stress
 Recovery after
 Immediately after
surgery,burns,trauma,s
surgery and crush
tress
injuries
Digestion of dietary proteins starts in the stomach. No digestion in mouth

 Most nitrogen in the diet is consumed in the form

of protein
 Proteins are too large to be absorbed by the
intestines
 They must be hydrolyzed to yield constituent
amino acids which can be absorbed
 Breakdown of proteins provide amino acids as fuels
 When amino acids are metabolized their nitrogen
must be disposed of in non toxic form
 Enzymes responsible for degrading proteins are
produced by (1) stomach,(2) pancreas and (3)
small intestine
Cont… 7 enzymes to convert large polypeptide to amino acid

Dietary protein (Large polypeptide)

↓pepsin in stomach

polypeptides and amino acids (Small polypeptide)

↓elastase,trypsin,chymotrypsin,carboxypeptidases enzymes acting on the small polypeptide to form
amino acid at the end
Oligopeptide and amino acid
↓aminopeptidases
Free Amino acids and dipeptides dipeptidase

inactive forms of enzymes (Trypsinogen, Chymotrypsinogen)

Protein is the last source of energy. After carbs and fats

Nitrogen metabolism is the same as protein metabolism as the main purpose of this metabolism is the removal of nitrogen. Nitrogen can
form ammonia and thus can be considered toxic. Ammonia is removed in the form of urea (Not toxic)
Cont…

stomach pancreas to intestinal

small intestine wall
pepsin Trypsin dipeptidases

Chymotrypsin

carboxypeptidase A

carboxypeptidase B

elastase
 OVERVIEW OF AMINO ACID METABOLISM

ENVIRONMENT ORGANISM add the protein

Bio-
structure
Ingested synthesis Protein
protein

from diet

major source of protein is our diet can use and produce

AMINO
ACIDS

Degradatio Purines
Pyrimidines
n Porphyrins
(required)
Carbon
Nitrogen
skeletons
(ketogenic) (glucogenic)
Urea Used for
energy pyruvate
acetoacetate by converting, α-ketoglutarate convert to glycolytic or Kerbs cycle
acetyl CoA the carbon
succinyl-CoA intermediates
skeleton gives
energy fumarate
if the protein is glycine = Carbon oxaloacetate
skeleton of glycine. If it gives glucogenic amino group (NH2) is removed in the breakdown and it is the one
then called glucogenic glycine......... converted to the non toxic form
(Depending on the product) The remaining structure without (NH2) is called the carbon skeleton
and can also convert to other forms (Glucogenic, Ketogenic,
Glucogenic + Ketogenic "If giving from both")
First phase of amino acid metabolism
Removal of α-NH2 groups by transamination and subsequent Almost all proteins go
oxidative deamination leads to formation of ammonia andalpha keto
through transamination
corresponding keto acid (carbon skeleton) glutarate "Keto acid" and
produce glutamate "Amino acid"
Different amino acids can form
Small amount of ammonia is excreted in urine but most isdifferent keto acids but it is always
used in synthesis of urea the same alpha keto glutarate and
giving glutamate because

Synthesis of urea is the most important route for disposing

of nitrogen from the body
Second phase of amino acid metabolism
The carbon skeletons are converted to common
intermediates of energy producing metabolic pathways
These intermediates can be metabolized to CO2,H2O,Fatty
acid or ketone bodies
Third phase of amino acid metabolism
Biosynthesis of amino acids
Biosynthesis of amino acid derivatives like
GABA,catecholamines,creatine,histamine,melanins,S-
adenosylmethionine etc
Removal of NH2 group and Transamination
 Presence of α- NH2 group keeps the amino acids safely locked from
OXIDATIVE DEAMINATION
 Removal of α- NH2 is essential for producing energy from amino acid and
is done by TRANSAMINATION
 TRANSAMINATION and OXIDATIVE DEAMINATION are reactions
that remove NH2 group from amino acids
 AND ultimately provide ammonia and aspartate, which are two sources of
urea nitrogen
 Transamination is defined as transfer of amino group from an amino acid
to a keto acid to form another ( new) amino acid and keto acid of the
original amino donor
 Most amino acids undergo transamination EXCEPT
lysine,threonine,proline and hydroxyproline
 Enzymes responsible for transamination are known as transaminases
Cont…
Transaminases can function in both amino acid catabolism and synthesis
α-NH2 groups of amino acids are ultimately transferred by transaminases
to form L- glutamate. PLP acts as coenzyme in transamination
reactions.
This nitrogen is released as ammonia (NH3) by a reaction catalysed by
glutamate dehydrogenase that uses NAD+ and NADP+ as coenzymes
ALT- Alanine amino transferase catalyses transfer of amino group to
form pyruvate and glutamate
AST- Aspartate amino transferase catalyses transfer of amino group to
form oxaloacetate and glutamate
synthesis
breakdown

COO− COO− COO− COO−

CH2 CH2 COO− CH2 COO− CH2
CH3 CH2 CH3 CH2 CH2 CH2 CH2 CH2
HC NH3+ + C O C O + HC NH3+ NH3+ NH3+
HC + C O C O + HC
COO− COO− COO− COO− COO− COO− COO− COO−
alanine -ketoglutarate pyruvate glutamate aspartate -ketoglutarate oxaloacetate glutamate
Aminotransferase (Transaminase) Aminotransferase (Transaminase)
Diagnostic value of amino transferases
 Are intracellular enzymes with low
levels found in plasma
 Presence of elevated levels indicate
damage to cells rich in these
enzymes
 AST and ALT are elevated in all liver
diseases
 ALT is more specific for liver disease
 AST is more sensitive because liver
contains more amount of AST. AST
also increases during MI
 Oxidative Deamination
 Net conversion of α-NH2 to NH3
 Glutamate is the only amino acid that undergoes
oxidative deamination catalyzed by Glutamate
dehydrogenase and regenerates α-keto glutarate.
Amino acid breakdown (Opposite is synthesis)

or NADP
if ammonia is not removed,
GDP after oxidative deamination
glutamate level is low and
ammonia accumulates

from transamination

 The α-ketoglutarate formed can be used in citric

acid cycle and glucose synthesis
 Oxidative deamination requires the combined
effort of transaminases and glutamate
dehydrogenases and is also referred to as
transdeamination
 Regulation of glutamate dehydrogenase
(GDH)
 Glutamate dehydrogenase is
allosterically inhibited by ATP and GTP

 Thus when energy levels are low, AA

degradation by GDH is high

 It is reversible reaction and functions

both in AA synthesis and catabolism.
 Ammonia Intoxication or hyperammonemia

 High ammonia would deplete glutamate – a

neurotransmitter & precursor for synthesis of the
neurotransmitter GABA. can affect central nervous system

 Depletion of glutamate & high ammonia level

would drive Glutamate Dehydrogenase reaction
to reverse: reverse bec glutamate is low

irreversible
glutamate + NAD(P)+ a-ketoglutarate +
NAD(P)H + NH4+
now alpha ketoglutarate is low, and TCA is not happening, and the brain is not getting energy "Harmful affect of hyperammonemia"

 The resulting depletion of a-ketoglutarate, an

essential Krebs Cycle intermediate, could impair
energy metabolism in the brain
Cont…
 Symptoms of ammonia intoxication are
tremors,slurred speech,blurred vision, coma
and ultimately death

TREATMENT
 limiting protein intake to the amount barely
adequate to supply amino acids for growth,
while adding to the diet the a-keto acid
analogs. take only the needed amount

 Liver transplantation has also been used,

since liver is the organ that carries out Urea
Cycle.
Overall flow of nitrogen in
amino acid catabolism
Fate of Ammonia produced by the tissues
 Ammonia produced by tissues is rapidly removed from
circulation by the liver and converted to
1. Glutamate
2. Glutamine
3. Finally to UREA
 Fate of Ammonia in cells other than the muscles

 Ammonia produced by tissues is Glutamine transports ammonia in

rapidly removed from circulation blood stream
by the liver and converted to The amide of glutamine provides
a non toxic storage and transport
1. Glutamate
form of ammonia
2. Glutamine Glutamine synthesis is catalyzed
3. Finally to UREA by glutamine synthase

toxic

AMMONIA + glutamate====glutamine synthase==== Glutamine "Amino acid"

CONH2 "amide bond"

non toxic
Glucose-Alanine Cycle in muscle cells

 Alanine transports
amino groups from
muscle to liver in non from muscle glycolysis

toxic form via

pathway called as
glucose alanine cycle back to muscle

In muscle amino
to bring new
 protein

groups are collected transamination

catalyzed by ALT

as glutamate
 Glutamate transfers
its amino group to transamination

pyruvate (obtained
Catalyzed by ALT

alpha keto...

from muslce oxidative deamination

glycolysis) in presence
of ALT to form alanine
Glucose Alanine cycle
 Alanine passes into the
blood and travels to the
liver
 Liver ALT transfers amino
group from alanine to α-
KG to form pyruvate and
Glutamate
 Glutamate enters
mitichondria and is
acted upon by GDH to
release ammonia
 Pyruvate by
gluconeogenesis is
converted to glucose .
Liver glucose travels
through blood to muscle
 Urea cycle UREA HAS 2 NITOGENS
Urea synthesis occurs in the LIVER
Kidneys only excrete urea in urine
 The urea cycle eht sa nwonk osla( ornithine cycle

 The Urea Cycle occurs mainly in liver

 Urea passes into the kidneys via the bloodstream and is finally
excreted in urine.
 The first two reactions of urea cycle occurs in mitochondrial
matrix while the next three reactions occur in the cytosol
 The 2 nitrogen atoms of urea enter the Urea Cycle as NH3
(produced mainly via Glutamate Dehydrogenase) and as the amino
N of aspartate.
 Synthesis of 1 molecule of urea requires 3 molecules of ATP plus 1
molecule each of ammonium ion and of α amino nitrogen of
aspartate
 Carbamoyl Phospahte Syntahase I (CPS I) is the rate limiting
enzyme and is activated by N-acetylglutamate
 CO2 "From TCA" + Ammonia "From oxidative deamination " 2 nitrogens (1 from ammonia and another from reaction 3 "
Aspartate") UREA CYCLE
urea is released
enzyme
ATP utilization
transporter

Activator

amino acid

the link between urea

cycle and TCA cycle

transporter
ENZYMES are imp
in the mitochondrial matrix

splits into Arginine and

fumarate

produced inside the matrix

gets out with a transporter
TOTAL 3 ATP consumed

know the reactions, enzymes, products

BUT NO STRUCTURE
 needed for the urea cycle
produced by TCA

TCA Cyle
intermediates
Fate of Urea
 Urea diffuses from the liver and is transported in
blood to the kidneys, where it is excreted in the
urine
 Small amount of urea diffuses from the blood to
intestine where it is cleaved to CO2 and NH3 by
bacterial urease
 In patients with kidney failure plasma urea
levels are elevated greater transfer of urea
from blood to gut . The intestinal action of urease on
this urea Hyperammonemia
Urea cycle disorders UCDs

5 reactions = 5 enzymes, without them, disorders occur

1. Hyperammonemia type 1. Is caused due to

the deficiency of CPS I
2. Hyperammonemia type 2. is caused due to
ornithine transcarbamoylase deficiency.
3. Citrullinemia : is caused due to the
deficiency of argininosuccinate synthase .
4. Argininosucciniaciduria ; is caused due to
absence of argininosuccinase
5. Hyperargininemia ; Is characterized by low
erythrocyte levels of arginase
Fate of carbon skeletons of Amino Acids
 Carbon skeletons of amino acids are converted
to SEVEN molecules which are either
intermediates of TCA cycle or substrates of
TCA cycle
 From here the carbon skeletons are diverted
to gluconeogenesis or ketogenesis or are
completely oxidised to CO2 and H2O
 The products formed are (1) OAA, (2) α KG,
(3) pyruvate, (4) fumarate (5) Succinyl CoA,
(6) Acetyl CoA,(7) Acetacetyl CoA
 Amino acids that form 1- 5 are called
Glucogenic and and which form 6-7 are
called ketogenic amino acids
 Glucogenic and ketogenic amino acids
others "PINK" are glucogenic and some gluco and ketogenic

Purely ketogenic bec only here

Glucogenic and ketogenic amino acids

 Amino acids, tryptophan, phenylalanine,

tyrosine, isoleucine and threonine are both
glucogenic and ketogenic.
 Only 2 amino acids are purely ketogenic they
are lysine and leucine.
 Amino acids that are purely glucogenic: Arg,
Glu, Gln, His, Pro, Val, Met, Asp, Asn,Ala, Ser,
Cys, and Gly.
 NO NEED FOR NAMES JUST KNOW HOW MANY

Biosynthesis Of Amino Acids

from diet
 Humans can
synthesize 12 amino
acids from glycolysis
and TCA cycle
intermediates. These
amino acids are
nutritionally non
essential
 Nutritionally
Essential amino acids
cannot be synthesized
in the human body
and have to be
provided in the diet
 Biosynthesis of amino
acids can be divided
into six families
 Biosynthesis of Amino acids
Essential in Capital letter
II. PEP + ERYTHROSE-4-Phosphate
I. OAA Non-essential in small

Aspartate LYS
Tyr
MET PHE TRP
Asparagine THR
Tyr
ILE
Biosynthesis of Amino acids

IV. Ribose-5-Phosphate

III. PYRUVATE

Ala VAL LEU

HIS
 Biosynthesis of Amino acids

V. α Ketoglutarate VI. 3-Phosphoglycerate

Glutamate
Serine

Arginine Glycine
Glutamine Cysteine
Pro
 know reactions
NO STRUCTURES
Conversion of Amino acids
to specialized products
 GABA-is synthesized from glutamate
 Histamine from histidine

cofactor
Catecholamines- are synthesized from tyrosine
 2 reactions

Serotonin is synthesized from tryptophan

Hormonal Regulation

 Insulin enough glucose = enough energy = no need for proteins for energy

 Glucose availability to cells increases

 Protein synthesis increases
 Glucagon opposite to insulin
 Protein synthesis decreases
 Protein degradation increases
Plasma Proteins: Classification
1- Simple proteins simply strait chain protein
The simple proteins are those which are made of
amino acid units only, joined by peptide bond. Upon
hydrolysis they yield mixture of amino acids and
nothing else
e.g. albumin and globulin
2- Conjugated proteins contain non protein group "Prosthetic group" that is imp for their
activity. Organic or non organic

Conjugated proteins are composed of simple proteins

combined with a non-proteinous substance
Protein + prosthetic group.
e.g. lipoprotein,phosphoprotein,hemoglobim
3- Derived proteins NOT NATURALLY OCCURING "normal or abnormal" Simple proteins go
into chemical reactions forming derived proteins
These are not naturally occurring proteins and are
obtained from simple proteins by the action of
enzymes and chemical agents e.g. peptones
 Plasma Protein Distribution

Fibrinogen
(4%) (1%)Other PlasmaProteins Albumin (60%)
Globulin (35%)
Globulin (35%)

Globulin Fibrinogen (4%)

Albumin
(35%)

(60%)
Other Plasma
Proteins (1%)
Other Plasma Proteins

 remaining one 1% of plasma

 Peptide hormones
 Insulin
 Prolactin protein hormones
 Glycoproteins
 TSH (thyroid- simulating hormone)
 FSH (follice stimulating hormone)
 LH (luteinizing hormone)
Serum protein electrophoresis

Serum proteins are

separated into 6 groups:
Albumin

α1 - globulins
α2 - globulins each one has several proteins

β1 - globulins
β2 - globulins
γ - globulins

Figure is found at http://www.sebia-usa.com/products/proteinBeta.html#

each has different region

bec B

called gamma
immunoglobulins

alpha
Common functions of plasma proteins
 Proteins are structural materials of animal body and
help in the growth of animal body
 buffer properties (maintenance of pH)
 build new tissues and maintain already present
tissues protein helps in healing wounds
 Some act as biochemical catalyst
 maintenance of osmotic pressure of blood
 Prevention of thrombosis (anticoagulant proteins)
 Defense against infection (antibodies, complement
proteins)
Albumin most abundant

 Functions include: HYPOALBUMINEMIA

 –Transport  Common Causes
 –Osmotic pressure  Decrease albumin
regulation synthesis:
 a. Liver disease (specially
 •Synthesized in the liver. chronic diseases).
 b. Malnutrition.
 •Deficiency: in liver  c. Alcoholism
disease and kidney  Increased albumin loss:
disease.
 a. Renal disease
(nephrotic syndrome).
 -Loss of albumin in urine
(proteinuria).
 b. Extensive burns:
 -Loss of albumin through
skin
 Non-protein Nitrogen Compounds
 Nitrogen containing compounds that are not proteins or
polypeptides
 The determination of non protein nitrogenous (NPN) substances
in the blood has traditionally been used to monitor renal
function.
 Useful clinical information is obtained from individual
components of NPN fraction
 Clinically signigicant NPN compounds are
urea,creatine,creatinine,uric acid etc. know the amount

normal amount in the blood