A Lecture in

BIOCHEMISTRY

CARBOHYDRATE
METABOLISM

Prepared by:
Dr. Leonisa O. Bernardo
Southern Luzon State University
Lucban, Quezon
(042)540-3961
• We need energy as we perform our daily
activities. Similarly, the cell needs supply of
cellular energy for the many functions that
support these activities.
• Likewise, energy is needed for biosynthesis of
small metabolic molecules and production of
macromolecules from these intermediates.
• Energy is required for mechanical work,
including muscle contraction and motility of
sperm cells.
• Our diet provides three sources of energy:

Carbohydrates Fats Proteins

-broken down into - broken down into - broken down into
simple sugars fatty acids and amino acids
glycerol
-The most readily used
source of energy.
 THE DIGESTIVE PROCESSES
Stomach secretes
Salivary glands HCl, which denatures
secrete amylase, proteins, and pepsin,
which digests which begins the
starch. degradation of
proteins.
Liver and
gallbladder Pancreas secretes
deliver bile salts to proteolytic enzymes
the duodenum to such as trypsin and
emulsify the large chymotrypsin that
fat globules into continue the
small fat droplets degradation of
accessible to the proteins. It also
action of secretes lipases that
pancreatic lipases. degrade lipids. These
act in the duodenum.
 Digestion of Carbohydrates

Digestion
• first stage in catabolism
• the breakdown of food into small molecules
• entails the (a) physical grinding, softening,
and mixing of food, as well as the (b) enzyme
catalyzed hydrolysis of carbohydrates,
proteins, and fats
• Carbohydrate digestion is necessary
because the gastrointestinal tract can only
absorb monosaccharides.
❑Digestion begins in the
mouth,

❑continues in the
stomach,

❑and concludes in the

small intestine
• The products of digestion are mostly small molecules
that are absorbed from the intestinal tract.
• The absorption happens through millions of tiny
projections (the villi) that provide a total surface as
big as a football field.
• Once in the blood stream, the small molecules
are transported into target cells where many
are farther broken down for the purpose of
releasing energy as their carbon atoms are
converted to carbon dioxide. C + O2 CO2 + Energy

• Others are
excreted, and
some are used
as building
blocks to
synthesize new
biomolecules.
 THE DIGESTION OF CARBOHYDRATES
❖The principal sites of dietary carbohydrate
digestion are the
• mouth and
• intestinal lumen
❖Digestion is rapid and
catalyzed by enzymes
glycoside hydrolase (glycosidases) that
hydrolyze glycosidic bonds.
❖Glycosidases are usually specific for the
structure and configuration of the glycosyl residue
to be removed as well as for the type of bond to be
broken.
 IMPORTANT TERMS IN DIGESTION OF
DIETARY CARBOHYDRAES
A. Salivary α-amylase
▪ The important dietary polysaccharides are of
plant (starch, composed of amylose and
amylopectin) and animal (glycogen) origin.
▪ During mastication, salivary α-amylase acts
briefly on dietary starch and glycogen,
hydrolyzing random α (1-4) bonds and β (1-4)
endoglucosidases
 THE DIGESTION OF CARBOHYDRATES
Dietary
Carbohydrates
(starch, glycogen,
sucrose, lactose)
Mouth Salivary α-amylase

Polysaccharides, sucrose,
lactose, and maltose
Stomach

Small intestine Pancreatic α-amylase

maltase, sucrase, lactase,

Monosaccharides
Absorption through
small intestine lining

Monosaccharides in
bloodstream
• The α-amylase in saliva catalyzes hydrolysis of
the glycosidic bonds in carbohydrates.

• Starch from plants and glycogen from meat are

hydrolyzed to give smaller polysaccharides and
the disaccharide maltose.
• Salivary α-amylase
continues to act on
dietary
polysaccharides in
the stomach until,
after an hour or so, it
is activated by
stomach acid (HCl).
• α-Amylase is
also secreted by
the pancreas
and enters the
small intestine,
where
conversion of
polysaccharides
to maltose
continues.
• Other enzymes from
the mucous lining of the
small intestines
hydrolyze maltose and
the dietary
disaccharides sucrose
and lactose to the
monosaccharides
glucose, fructose, and
galactose,
• which are then
transported across the
intestinal wall into the
bloodstream.
GLUCOSE METABOLISM
 Metabolic Pathways of Glucose
Name Derivation of name Function
Glycolysis glyco-, glucose (from Conversion of glucose
Greek word meaning sweet) to pyruvate
-lysis, decomposition or
rupture
Gluconeogenesis gluco-, glucose Synthesis of glucose
-neo-, new from amino acids,
pyruvate, and other
-genesis, creation noncarbohydrates
Glycogenesis glyco(gen)-, glycogen – Synthesis of glycogen
genesis, creation from glucose

Glycogenolysis glycogen-, glycogen Breakdown of glycogen

to glucose
-lysis, decomposition
Pentose pentose-, a five-carbon Conversion of glucose
phosphate sugar phosphate to five-carbon sugar
pathway phosphate
 Glucose Metabolism: An Overview
• Glucose is the major fuel for our bodies.
– It yields the energy carried by ATP.
• The initial metabolic fate of glucose is conversion into
acetyl-SCoA , the common intermediate in the
catabolism of all foods.
– The acetyl-SCoA proceeds down the central pathway of
metabolism to the ultimate formation of ATP.
• When glucose enters a cell from the bloodstream, it is
immediately converted to glucose 6-phosphate.
• Once this phosphate is formed, glucose is trapped within
the cell because the phosphate cannot cross the cell
membrane.
• The formation of glucose-6-phosphate is highly
exergonic (spontaneous) and not reversible, thereby
committing the initial substrate to subsequent reactions.
Pathways available to glucose 6-phosphate
1. pentose phosphate pathway
2. Glycolysis
3. glycogenesis
PHOSPHORYLATION & GLYCOLYSIS

• When energy is needed, glucose 6-phosphate moves

down the central catabolic pathway, proceeding via the
reactions of glycolysis to pyruvate and then to acetyl-S-
coenzyme A, which enters the citric acid cycle.

Phosphorylation Glycolysis

2 2

Pyruvate Acetyl-SCoA
Glucose Glucose 6-phosphate
• 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-SCoA into the pathways of lipid metabolism
rather than the citric acid cycle.
• Glucose-6-phosphate can also enter the pentose
phosphate pathway when a cell’s need for NADPH or
ribose-6-phosphate exceeds its need for ATP. It yields
two important products:
1) Coenzyme NADPH, a reducing agent that is essential for
various chemical reactions
2) 5- phosphate of the five-carbon sugar ribose, which is
necessary for the synthesis of nucleic acids (DNA and
RNA)
 Test Yourself Question (TYQ-3.1)

• Problem 1. Name each of the following

pathways:
(a) pathway for release of glucose from glycogen
(b) pathway for synthesis of glucose from lactate
(c) pathway for synthesis of glycogen

• Problem 2. Name the synthetic pathways that

have glucose 6-phosphate as their first reactant.
 GLYCOLYSIS
• is a series of 10 enzyme-catalyzed reactions that breaks
down each glucose molecule into two pyruvate
molecules, and in the process yields two ATPs and two
NADHs.
• The overall reaction of glycolysis which occurs in the
cytoplasm is presented simply as:

+ 2 NAD+ + 2 ADP + 2
ADP + 2 Pi

D-Glucose 2 + 2 NADH + 2 H+ + 2 ATP + 2 H2O

Pyruvate
 Structures of Related Molecules
Adenosine 5'-triphosphate (ATP) derived from
Adenosine diphosphate (ADP) adenine and
Adenosine monophosphate (AMP) ribose

adenine

ribose
 ATP
ADP-ATP Cycle

ADP

AMP
Structure of NAD+/NADH

nicotinamide adenine dinucleotide

 Step 1. Glucose undergoes reaction
with ATP to yield glucose 6-
phosphate + ADP in a reaction
catalyzed by hexokinase.
Step 2. Isomerization of glucose 6-
phosphate yields fructose 6-
phosphate. The reaction is
catalyzed by the mutase enzyme,
glucose 6-phosphate isomerase.
2- Step 3. Fructose 6-phosphate reacts
with a second molecule of ATP to
O3 P yield fructose 1,6-biphosphate plus
– ADP, Phosphofructokinase, the
enzyme for step 3, provides a major
control point in glycolysis.
Step 4. The six-carbon chain of
fructose 1,6-biphosphate is cleaved
into two three-carbon pieces by the
enzyme aldolase.
Step 5. The two products of step 4 are
both three-carbon sugars, but only
glyceraldehyde 3-phosphate can
continue in the glycolysis pathway.
Dihydroxyacetone phosphate must
first be isomerized by the enzyme
triose phosphate isomerase.
• Step 6. Two reactions occur as glyceraldehyde
3-phosphate is first oxidized to a carboxylic acid
and then phosphorylated by the enzyme
glyceraldehyde 3-phosphate
dehydrogenase. The co enzyme nicotinamide
adenine dinucleotide (NAD) and inorganic
phosphate ion (HOPO32-) are required.
• Step 7. A phosphate group from 1,3-
biphosphoglycerate is transferred to ADP,
resulting in synthesis of ATP, and catalyzed by
phosphoglycerate kinase.
• Step 8. A phosphate group is next transferred
from carbon 3 to carbon 2 of phosphoglycerate
in a step catalyzed by the enzyme
phosphoglycerate mutase.
• Step 9. Loss of water from 2-phosphoglycerate
produces phosphoenolpyruvate (PEP). The
dehydration is catalyzed by the enzyme
enolase.
• Step 10. Transfer of the phosphate group from
phosphoenolpyruvate to ADP yields pyruvate
and generates ATP, catalyzed by pyruvate
kinase.
• Steps 1-3 of Glycolysis. PHOSPHORYLATION
– Glucose is carried in blood to cells where it is transported
across the cell membrane.
– As soon as it enters the cell, glucose is phosphorylated in
step 1 of glycolysis, which requires an energy investment
from ATP.
– Phosphorylation is addition of –PO32- group.
– This is the first of three highly exergonic and irreversible
steps in glycolysis. From here on, all intermediates are
sugar phosphates and are trapped within the cells
because phosphates cannot cross cell membranes. The
product of step 1, glucose 6-phosphate, is an allosteric
inhibitor for the enzyme for this step (hexokinase), which
thus plays an important role in the elaborate and delicate
control of glucose metabolism.
• Step 2 is the isomerization of glucose 6-
phosphate to fructose 6-phosphate.
– The enzyme (glucose 6-phosphate isomerase) acts
by converting glucose 6-phosphate (an aldohexose)
to fructose 6-phosphate (a ketohexose).
– The result is the conversion of the six-membered
glucose ring to a five membered ring with a –CH2OH
group, which prepares the molecule for addition of
another phosphoryl group in the next step.
• Step 3 makes a second energy investment as
fructose 6-phosphate is converted to fructose 1,6-
biphosphate by reaction with ATP in another
exergonic reaction.
– Step 3 is another major control point for glycolysis.
– When the cell is short of energy, ADP and AMP
concentrations build up and activate the step 3 enzyme,
phosphofructokinase.
– When energy is in good supply, ATP and citrate build up
and allosterically inhibit the enzyme.
– The outcome of steps 1-3 is formation of a molecule ready
to be split into the two-carbon intermediates that will
ultimately become two molecules of pyruvate.
• Steps 4 and 5 of Glycolysis: Cleavage and
Isomerization
– Step 4 converts the six-carbon biphosphate from step 3
into two three-carbon monophosphates, one an aldose
phosphate and one a ketose phosphate. The bond
between carbons 3 and 4 in fructose 1,6-biphosphate
breaks, and a C=O group is formed.

fructose bisp
hosphate ald
olase

D-
β-D-Fructose 1,6-bisphosphate glyceraldehyde 3-p dihydroxyacetone
(F1,6BP) hosphate phosphate
(GADP) (DHAP)
– The two three-carbon sugar phosphates produced in
step 4 are isomers that are interconvertible in an
aldose-ketose equilibrium (step 5).
– Only glyceraldehyde 3-phosphate(GADP) can
continue on the glycolysis pathway, thus, DHAP is
converted to GADP.

triosephosphate i
somerase
(TPI)
an isomerase

D-
Dihydroxyacetone
phosphate glyceraldehyde 3-p
hosphate
(DHAP)
(GADP)
 – As the glyceraldehyde 3-phosphate reacts in step 6,
the equilibrium of step 4 is shifted to the right.
– The overall result of steps 4 and 5 is therefore the
production of two molecules of glyceraldehyde 3-
phosphate.
• Steps 1-5 are referred to as the energy investment or
preparatory part of glycolysis. So far, two ATPs have
been invested and no income has been earned, but the
stage has been set for a small profit.
• Since one glucose molecule gives two glyceraldehyde 3-
phosphates that pass separately down the rest of the
pathway, steps 6-10 of glycolysis take place twice for
every glucose
• Steps 6-10 of Glycolysis: Energy Generation or
Payoff Phase
– The second half of glycolysis is devoted to generating molecules
with phosphate groups that can be transferred to ATP.
• Steps 6 is the oxidation of glyceraldehyde 3-phosphate
to 1,3-biphosphoglycerate.
– NAD+ is the oxidizing agent.
– Some of the energy from the exergonic oxidation is
captured in NADH, and some is devoted to forming the
phosphate.
– This is the first energy-generating step of glycolysis.
– The triose sugars are dehydrogenatedThe triose sugars
are dehydrogenated and inorganic phosphateThe triose
sugars are dehydrogenated and inorganic phosphate is
added to them, forming 1,3-bisphosphoglycerate.
– The hydrogen is used to reduce two molecules of NAD, a
hydrogen carrier, to give NADH + H+.
• Step 7 generates the first ATP of glycolysis by
transferring a phosphate group from 1,3-
biphosphoglycerate to ADP.
– Because this step occurs twice for each glucose molecule,
the ATP energy balance sheet in glycolysis is even after
step 7.
– Two ATPs were spent in steps 1-5, and now they’ve been
replaced.

• Steps 8 and 9 – an isomerization followed by

dehydration – generate phophoenolpyruvate, the
second energy-providing phosphate of glycolysis.
• Step 10 is highly exergonic, irreversible transfer of a
phosphate group to ADP. The large amount of free
energy released is accounted for by rearrangement of
the less stable enol form of pyruvate to be more stable
keto from.
• The overall reaction of glycolysis which occurs in
the cytoplasm is presented simply as:
C6H12O6 + 2 NAD+ + 2 ADP + 2 P
D-Glucose

2 (CH3(C=O)COO¯ + 2 ATP + 2 NADH + 2 H+

Pyruvate

• Thus, the net result of glycolysis are:

– Conversion of glucose to two pyruvates
– Production of two ATPs
– Production of two molecules of reduced coenzyme
NADH from NAD+
 Test Yourself Question (TYQ-3.2)
• Problem 3. Identify the two pairs of steps in
glycolysis in which phosphate intermediates are
synthesized and their energy harvested as ATP.
• Problem 4. Identify each step in glycolysis that
is an isomerization.
• Problem 5. Verify the isomerization that occurs
in step 2 of glycolysis by drawing the open-chain
forms of glucose 6-phosphate and fructose 6-
phosphate.
 REGULATION OF GLYCOLYSIS

Energy-harvesting pathways, such as glycolysis, are

responsive to the energy needs of the cell.
• What happen if there is a demand for ATP? The reaction
speed up.
• What happen if there is abundant ATP? They slow down
to meet the energy requirement of the cell.
• What is the mechanism for the control of the rate of
glycolysis? The use of allosteric enzymes. In addition to
the active site, which binds the substrate, allosteric
enzymes have an effector binding site, which binds a
chemical signal that alters the rate at which the enzyme
catalyzes the reaction.
 Test Yourself Question (TYQ-3.3)

• What are chemical signals or effectors?

Name these effectors.
• What is the role of hexokinase?
• What is the role of Phosphofructokinase?
• What is the role of pyruvate kinase?
ENTRY OF OTHER SUGARS INTO GLYCOLYSIS

The major monosaccharides from digestion

other than glucose also eventually join the
glycolysis pathway.
• Fructose (from fruits or hydrolysis of the
disaccharide sucrose) is converted to
glycolysis intermediates in two ways:
1. In muscle it is phosphorylated to fructose 6-
phosphate, and
2. In the liver, it is converted to glyceraldehyde 3-
phosphate
•Galactose from hydrolysis of the disaccharide
lactose is converted to glucose 6-phosphate by
a five-step pathway.
⮚A hereditary defect affecting any of the
enzymes in this pathway can be a cause of
galactosemia.
•Manose is a product of the hydrolysis of plant
polysaccharides other than starch. It is
converted by hexokinase to a 6-phosphate,
which then undergoes a multistep, enzyme-
catalyzed rearrangement and enters glycolysis
as fructose 6-phosphate.
 The Fate of Pyruvate
• The conversion of glucose to pyruvate is a
central metabolic pathway in most living
systems.
• The further reactions of pyruvate depend on
(1) metabolic conditions
⮚ Under normal oxygen-rich (aerobic) conditions,
pyruvate is converted to acety-SCoA.
⮚ This pathway, however, is short-circuited in some
tissues, especially when there’s not enough oxygen
(anaerobic) conditions. Under anaerobic conditions,
pyruvate is instead reduced to lactate. When
sufficient oxygen again becomes available, the lactate
is recycled to pyruvate..
⮚ A third pathway for pyruvate is conversion back to
glucose by gluconeogenesis. This pathway is
essential when the body is starved for glucose. The
pyruvate for gluconeogenesis may come not only
from glycolysis, but also from amino acids or glycerol
from lipids.
(2) the nature of the organism
⮚ Yeast is an organism with a different pathway for
pyruvate, one that we put to use in a variety of ways.
Yeast converts pyruvate to ethanol under anaerobic
conditions.
Aerobic Oxidation of Pyruvate to Acetyl-SCoA
• For aerobic condition to proceed, the pyruvate first
diffuses across the outer mitochondrial membrane
from the cytosol where it was produced.
• Then it must be carried by a transporter protein
across the otherwise impenetrable inner
mitochondrial membrane.
• Once within the mitochondrial matrix, the pyruvate
encounters the pyruvate dehydrogenase complex, a
large multienzyme complex that catalyzes the
conversion of pyruvate to acetyl-SCoA.
NAD+ NADH/H+

+ HS-CoA CH3C-SCoA + CO2

 Anaerobic Reduction to Lactate
Why does pyruvate take an alternative pathway when oxygen is
in short supply? Since no oxygen has been needed in glucose
catabolism thus far, what is the connection?
• The problem lies with NADH formed in step 6 of
glycolysis. Under aerobic conditions, NADH is
continually reoxidized to NAD+ during electron transport,
so NAD+ is in good supply.
• If electron transport slows down because of insufficient
oxygen, NADH concentration build up, NAD+ is in short
supply,and glycolysis can’t continue.
• An alternative way to reoxidize NADH is therefore
essential because glycolysis must continue – it is the
only available source of fresh ATP.
• The reduction of pyruvate to lactate solves the
problem. NADH serves as the reducing agent
and is reoxidized to NAD+, which is then
available in the cytosol for glycolysis.
• Lactate formation serves no purpose other than
NAD+ production, and the lactate is reoxidized to
pyruvate when oxygen is available.
O O NADH/H+ NAD HO O
CH3–C–C–O¯ CH3–C–C–O¯
Anaerobic conditions

Pyruvate Aerobic conditions

Lactate
• Red blood cells have no mitochondria and
therefore always form lactate as the end
product of glycolysis.
• Tissues where oxygen is in short supply
also rely on anaerobic production of ATP
by glycolysis. Examples are the cornea of
the eye, where there is little blood
circulation, and muscles during intense
activity.
• The resulting buildup of lactate in the
muscles causes fatigue and discomfort.
 Alcoholic Fermentation
• Microorganisms often must survive in the absence of
oxygen and have evolved numerous anaerobic
strategies for energy production, generally known as
fermentation.
• When pyruvate undergoes fermentation by yeast, it is
converted to ethanol plus carbon dioxide. The process
called alcoholic fermentation, is used to produce beer,
wine, and other alcoholic beverages and also to make
bread. The carbon dioxide causes the bread to rise, and
the alcohol evaporates during baking.
• The first leavened, or raised, bread was probably made
by accident when airborne yeasts got into the dough.
The tempting aroma of baking bread includes the aroma
of alcohol vapors. Beer can be made by exposing the
mash to outside air, where the airborne yeasts drift in
from the surroundings.
 Test Yourself Question (TYQ-3.4)

Make a summary of the 10-steps process of

glycolysis in matrix form. Write the reactant in
first column, the enzyme in the second column
and the products in the third column.
That ends our discussion.
Thank you!