Monosaccharides

Have only one sugar group

• Mono = One
• Saccharide = Sugar
 Pentoses ; 5 Carbon Sugars
• In DNA and RNA structure
 Glucose
• Blood sugar
 Fructose
• Fruit sugar
• Honey sugar
• Sperm’s energy source
 High Fructose Corn Syrup
‘’ HFCS’’

• 55% Fructose/45% Glucose which is used to sweeten soft

drinks and many foods
Am J Clin Nut 2004 Apr;79(4):537-43:
Consumption of high-fructose corn syrup in
beverages may play a role in the epidemic of obesity
Glycosidic bond between two hexoses produces;
Disaccharide
Glycogen ; Storage form of energy in the body
If Liver and Intramuscular
Glycogen depots are full;
Excessive calories stored as
FAT
Starch Molecule has Alpha 1,4 Glycoside Bonds
Between Glucose Monomers
Cellulose has Beta 1,4 Glycoside Bonds
Between Glucose Monomers
• We don’t have Cellulase enzyme to digest cellulose
so;
• Humans can not digest Cellulose
 If Serum Amylase
MUMP or Pancreatitis
Lactose ; Milk Sugar
 Lactose Intolerance
‘’ Intestinal Lactase Enzyme Deficiency ‘’
Symptoms

• Diarrhea, nausea, abdominal cramps, bloating, gas

 Glucuronic Acid
‘’Detoxification Molecule’’

• Insoluble Toxic molecules are conjugated by

Glucuronic acid so
• Become soluble in water and
• Can be excreted by urine
METABOLISM
• Complex molecules are broken down into their component
simple building blocks
• Proteins are degraded to amino acids
• Polysaccharides to monosaccharides
• Fats (Triglycerides) to free fatty acids and glycerol
Glycolysis
• Occurs in CYTOSOL in all tissues
• Proceeds through a series of
phosphorylated intermediates
• Starts with synthesis of
Glucose-6-phosphate (Glc-6-P)
• Involves 10 enzymatically
catalyzed steps
• 2 molecules of ATP are
expended
AEROBIC GLYCOLYSIS
• 4 ATP molecules are produced
• 1 molecule of Glucose is eventually
converted into 2
molecules of Pyruvate (Aerobic)or
2 molecules of Lactate (Anaerobic)
• Outcome; a net 2 ATP and 2 NADH
per mole of Glucose converted into
Pyruvate
• Most glycolytic
intermediates serve as
Branch points to other
metabolic pathways
• Glucose metabolism
intersects with
metabolism of;
• Lipids, proteins, and
nucleic acids, as well as
other pathways of
carbohydrate metabolism
Medical Biochemistry Baynes JW, Dominiczak MH
• Mature RBCs lack mitochondria
• Therefore, RBCs are completely dependent on
Glycolysis for ATP production
• Anemia observed in Glycolytic enzyme
deficiencies is a consequence of the reduced rate
of Glycolysis
• Premature death and lysis of RBCs result in
HEMOLYTIC ANEMIA
ANAEROBIC GLYCOLYSIS
• Conversion of Glucose to Lactic acid
• Called Anaerobic glycolysis
• Can occur without oxygen
• Allows the production of ATP in tissues that lack
mitochondria (e.g. red blood cells or in cells
deprived of sufficient oxygen)
 Cori Cycle
• Lactic acid produced by exercising muscles is converted to
glucose by the liver then fed back to the muscles
 During intense exercise
• Lactic acid accumulates in muscle
• Causes a drop in the intracellular pH, potentially resulting
in cramps ( Lactic acidosis )
• Much of this lactic acid eventually diffuses into
bloodstream and
• Can be used by Liver to make Glucose (= Gluconeogenesis)
In Liver; Glucose synthesis from Lactic acid
 Krebs Cycle = Citric acid Cycle =
TCA (= Tri Carboxylic Acid Cycle)
• Located in Mitochondrion
• A shared pathway for
metabolism of all fuels
• Begins with Acetyl CoA
• Acetyl CoA; Common product of
catabolism of lipid,
carbohydrate, and proteins,
• Produce majority of Reduced
Coenzymes that are used for
Medical Biochemistry Baynes JW, Dominiczak MH
ATP generation in ETC
• TCA cycle has 2 major
functions:
• Energy production and
Biosynthesis
 FUNCTIONS OF TCA CYCLE

• Acetyl-CoA is oxidized in TCA cycle

to produce; Reduced Coenzymes
• 3 NADH
• 1 FADH2 and
• 1 GTP
• Reduced nucleotides provide
energy for ATP synthesis by ETC
 TCA Cycle

• In addition to its role in

Catabolism;
• Participates in Synthesis of
Glucose from Amino acids and
Lactate during Starvation and
Fasting (Gluconeogenesis)
• Participates in Conversion of
Carbohydrates to Lipid
following a carbohydrate rich
meal (Lipogenesis)
 ENERGY PRODUCED BY KREBS CYCLE
Oxidation of 1 NADH by ETC leads to formation of 3 ATP
Oxidation of 1 FADH2 yields 2 ATP
Total yield of ATP from Oxidation of 1 molecule Acetyl CoA
(Using both Substrate level and Oxidative phosphorylation);
• Brain, Red blood cells, Kidney medulla, Lens and Cornea of
the eye, and Exercising muscle, require a continuous
supply of GLUCOSE as a metabolic fuel
• Liver glycogen, an essential postprandial source of glucose,
can meet these needs for only 10–18 hours in the absence
of dietary intake of carbohydrate
 Gluconeogenesis
• Process of synthesizing Glucose or Glycogen from
Noncarbohydrate precursors
• During a prolonged fast;
• Liver Glycogen stores are depleted
• Glucose is formed from Noncarbohydrate precursors such
as;
• Glucogenic amino acids (Alanine, Glutamine), Lactic acid,
Glycerol
• Major gluconeogenic tissues; Liver and Kidney
Glucogenic amino acids
Carbon skeletons for Gluconeogenesis are
Provided from 3 primary sources
• Lactic acid produced in tissues such as RBCs and
Muscle
• Amino acids derived from Muscle protein
• Glycerol released from Triglycerides during Lipolysis
in Adipose tissue
• A supply of glucose is necessary especially for the
Nervous system and RBCs
• After an overnight fast;
• Glycogenolysis and Gluconeogenesis make
approximately equal contributions to blood glucose
• As Glycogen reserves are depleted, so;
• Gluconeogenesis becomes progressively more
important
 Gluconeogenesis
• During an overnight fast;
• Approximately 90% of gluconeogenesis occurs in the liver
• The remaining 10% occurs in the kidneys
 Gluconeogenesis
• During prolonged fasting;
• Kidneys become major glucose-producing organs
• Contributes about 40% of the total glucose production
• Failure of Gluconeogenesis is usually FATAL
• Hypoglycemia causes brain dysfunction, which can
lead to coma and death
• Glucose is also important in maintaining adequate
concentrations of intermediates of Krebs cycle
• Gluconeogenesis clears;
• Lactic acid produced by Muscle and RBCs and
• Glycerol produced by Adipose tissue
 Muscle protein is the major precursor of blood
glucose during fasting and starvation;
• Rate of gluconeogenesis is often limited by the
availability of substrate, including Proteolysis rate
in Muscle or, in some cases, Muscle mass
• During prolonged fasting, malnutrition, or
starvation;
• We lose both Adipose and Muscle mass
Primary Sources of Blood glucose

Diet

Degradation of glycogen

Gluconeogenesis
• Dietary intake of glucose and
• Glucose precursors, such as starch , disaccharides,
and monosaccharides, is sporadic
• Depends on the diet
• Is not always a reliable source of blood glucose
• Gluconeogenesis can provide sustained synthesis of
glucose, but it is somewhat slow in responding to a falling
blood glucose level
• Therefore, the body has developed mechanisms for storing
a supply of glucose in a rapidly mobilizable form, namely,
GLYCOGEN
• In the absence of a dietary source of glucose;
• Glycogen is rapidly released from liver and kidney glycogen
• Muscle glycogen is extensively degraded in exercising
muscle to provide energy
• The main stores of glycogen are found in skeletal muscle
and liver
• Most other cells store small amounts of glycogen for their
own use
• The function of muscle glycogen is to serve as a fuel
reserve for ATP synthesis during muscle contraction
• Liver glycogen maintains the blood glucose particularly
during the early stages of fasting
• Liver glycogen can maintain blood glucose for 10–18 hours
• When glycogen stores are depleted;
• Specific tissues synthesize glucose using amino acids from
body’s proteins
• An alternate mechanism for metabolizing a
monosaccharide is to convert it to a Polyol (Sugar alcohol)
by the reduction of an aldehyde group
• Sorbitol is produced from Glucose
 Synthesis of Sorbitol
• Aldose reductase reduces glucose, producing SORBITOL
• Aldose reductase is found in many tissues, including Lens,
Retina, Liver , Kidney, Red blood cells,Nerve cells, Ovaries
and Seminal vesicles
• In Liver , Ovaries, and Seminal vesicles, there is a second
enzyme; Sorbitol dehydrogenase which can oxidize the
Sorbitol to produce Fructose
Fructose; Sperms’ energy source
Effect of hyperglycemia on sorbitol metabolism

• In hyperglycemia and uncontrolled diabetes;

• Large amounts of glucose may enter cells
• Elevated intracellular glucose concentrations and
• An adequate supply of NADPH cause Aldose reductase to
produce high levels of Sorbitol
Effect of hyperglycemia on sorbitol metabolism

• Sorbitol cannot pass efficiently through cell membranes

and, in turn, remains trapped inside the cell
• When Sorbitol dehydrogenase is low or absent ( In retina,
lens, kidney, and nerve cells)
• Sorbitol accumulates in these cells, causing strong osmotic
effects and, therefore, cell swelling as a result of water
retention
• Osmotic effect of Sorbitol produces changes in
tissues when they accumulate in abnormal
amounts e.g. Cataract of lenses
Effect of hyperglycemia on sorbitol metabolism

• Some of the pathologic alterations associated with

diabetes can be attributed, in part, to this phenomenon,
including;
• Cataract formation
• Peripheral neuropathy
• Microvascular problems leading to Nephropathy and
Retinopathy
Glycation of Hemoglobin A
• Nonenzymatic attachment of Glucose to Hemoglobin A in
RBCs occurs in normal individuals
• Forms HbA1c
• Increased in patients with Diabetes mellitus
• HbA1c reflects average plasma Glucose over the previous 8
to 12 weeks
• It can be performed at any time of the day
• Does not require any special preparation such as fasting
• These properties have made it the preferred test for
assessing glycaemic control in Diabetics
 Pentose Phosphate Pathway
• Occurs in the cytosol of the cell
• No adenosine triphosphate (ATP) is directly consumed or
produced in the cycle
• Provides a major portion of the body’s NADPH, which
functions as a biochemical Reductant
 NADPH
• Required for Fatty acid synthesis and
• Steroids synthesis (Cholesterol, Sex hormones)
 NADPH
• Glutathione; Antioxidant in Red blood cells
• Glutathione is regenerated by NADPH dependent
Glutathione reductase enzyme
• Reduced glutathione is essential to maintain the integrity
of RBC membrane
• Deficiency of NADPH in RBCs lead to HEINZ BODIES
formation

A case oriented approach towards biochemistry

 Pentose Phosphate Pathway
• Produces Ribose 5-phosphate, required for the Nucleotides
biosynthesis

.
 PENTOSE PHOSPHATE PATHWAY
‘’Glucose 6 phosphate Dehydrogenase Reaction’’
Glucose 6 phosphate dehydrogenase deficiency
@
Favism
• If G 6 PDH enzyme deficient person eats FAVA
• Cause hemolysis of red blood cells
• Red blood cells contain Hemoglobin
• Hemoglobin = Hem + Globin
• Hem is catabolysed to Bilirubin (YELLOW)
FAVISM
GLUCOSE 6-PHOSPHATE DEHYDROGENASE
DEFICIENCY
• A hereditary disease characterized by hemolytic anemia
• Caused by the inability to detoxify oxidizing agents
• The most common disease producing enzyme abnormality
in humans
• Affects more than 400 million individuals worldwide
• The life span of individuals with a severe form of G6PD
deficiency may be shortened as a result of complications
arising from chronic hemolysis