Dept.

of Food Technology and Nutrition Science

Noakhali Science and Technology University

FTNS-3101
Nutritional Biochemistry-1
METABOLISM OF CARBOHYDRATES

Rahanur Alam
M.Sc. (TUM, Germany), B.Sc. (Hons) (DU)
Lecturer
Dept. of Food Technology and Nutrition Science
Noakhali Science and Technology University
Dept. of Food Technology and Nutrition Science
Noakhali Science and Technology University

DIGESTION OF CARBOHYDRATES
Glycogen, starch and disaccharides (sucrose, lactose and
maltose) are hydrolyzed to monosaccharide units in the
gastrointestinal tract.

The process of digestion starts in the mouth by the

salivary enzyme –amilase.
The time for digestion in mouth is limited.
Salivary -amilase is inhibited in stomach due to the
action of hydrochloric acid.
Another -amilase is produced in pancreas and is
available in the intestine.
Dept. of Food Technology and Nutrition Science
Noakhali Science and Technology University

-amilase hydrolyzes the -1-4-glycosidic bonds randomly to

produce smaller subunits like maltose, dextrines and
unbranched oligosaccharides.

-amilase
Dept. of Food Technology and Nutrition Science
Noakhali Science and Technology University

The intestinal juice contains enzymes hydrolyzing

disaccharides into monosaccharides (they are produced in
the intestinal wall)
Sucrase hydrolyses sucrose into glucose and fructose

Glucose

sucrase

Fructose
Sucrose
 Galactose lactase Glucose

Lactase hydrolyses
lactose into glucose
and galactose

Lactose
Glucose maltase Glucose

Maltase hydrolyses
maltose into two
glucose molecules

Maltose
 Dept. of Food Technology and Nutrition Science
Noakhali Science and Technology University

ABSORPTION OF CARBOHYDRATES
Only monosaccharides are absorbed

The rate of absorption: galactose > glucose > fructose

Glucose and galactose from the intestine into endothelial cells
are absorbed by secondary active transport
Dept. of Food Technology and Nutrition Science
Noakhali Science and Technology University

Carrier protein is specific for D-glucose or D-galactose.

L-forms are not transported.

There are competition between glucose and galactose for
the same carrier molecule; thus glucose can inhibit
absorption of galactose.

Fructose is absorbed from intestine into intestinal cells

by facilitated diffusion.

Absorption of glucose from intestinal cells into bloodstream

is by facilitated diffusion.
Dept. of Food Technology and Nutrition Science
Noakhali Science and Technology University

Transport of glucose from blood into cells of different organs is

mainly by facilitated diffusion.
The protein facilitating the glucose transport is called
glucose transporter (GluT).
GluT are of 5 types.
GluT2 is located mainly in hepatocytes membranes (it transport
glucose into cells when blood sugar is high);
GluT1 is seen in erythrocytes and endothelial cells;

GluT3 is located in neuronal cells (has higher affinity to glucose);

GluT5 – in intestine and kidneys;

GluT - in muscles and fat cells.

Dept. of Food Technology and Nutrition Science
Noakhali Science and Technology University

The fate of glucose molecule in the cell

Glucose
Pentose phosphate
Glycogenogenesis pathway supplies
(synthesis of the NADPH for lipid
glycogen) is synthesis and
activated in well Glucose-6-
pentoses for nucleic
fed, resting state acid synthesis
phosphate

Ribose,
Glycogen
NADPH
Pyruvate Glycolysis
is activated if
energy is required
Dept. of Food Technology and Nutrition Science
Noakhali Science and Technology University

Glycolysis is the earliest discovered and most important process

of carbohydrates metabolism.
Glycolysis – metabolic pathway in which glucose is
transformed to pyruvate with production of a small
amount of energy in the form of ATP or NADH.

Glycolysis is an anaerobic process (it does not require oxygen).

Glycolysis pathway is used by anaerobic as well as aerobic

organisms. In glycolysis one molecule of glucose is converted
into two molecules of pyruvate.

In eukaryotic cells, glycolysis takes place in the cytosol.

Dept. of Food Technology and Nutrition Science
Noakhali Science and Technology University

Pyruvate can be further metabolized to:

(1) Lactate or ethanol (anaerobic conditions)
(2) Acetyl CoA (aerobic conditions)
• Acetyl CoA is further oxidized to CO2 and H2O via the citric
acid cycle
• Much more ATP is generated from the citric acid cycle
than from glycolysis

Acetyl CoA
• Catabolism of glucose in
aerobic conditions via
glycolysis and the citric
acid cycle
 The glycolytic pathway consist of ten enzyme-
catalyzed reactions that begin with a glucose and
split it into two molecules of pyruvate
Glycolysis
(10 reactions)
can be
divided into
three stages
• In the 1st stage
(hexose stage)
2 ATP are
consumed per
glucose
• In the 3rd stage
(triose stage)
4 ATP are
produced
per glucose
• Net: 2
ATP
produced per
Stage 1, which is the conversion of glucose into
fructose 1,6-bisphosphate, consists of three steps: a
phosphorylation, an isomerization, and a second
phosphorylation reaction.
The strategy
of these
initial steps
in glycolysis
is to trap
the glucose
in the cell
and form a
compound
that can be
readily
cleaved into
phospho-
rylated
three-
carbon units.
Stage 2 is the cleavage of the fructose
1,6-bisphosphate into two three-
carbon fragments dihydroxyacetone phosphate
and glyceraldehyde 3-phosphate.

Dihydroxyacetone phosphate and

glyceraldehyde 3- phosphate are readily
interconvertible.
In stage 3,
ATP is
harvested
when the
three-
carbon
fragments
are
oxidized to
pyruvate.
Glycolysis Has 10 Enzyme-Catalyzed Steps
• Each chemical reaction prepares a substrate for the next
step in the process
1. Hexokinase
• Transfers the -phosphoryl of ATP to glucose C-6 oxygen to
generate glucose 6-phosphate (G6P)
• Four kinases in glycolysis: steps 1,3,7, and 10
• All four kinases require Mg2+ and have a similar mechanism
 Properties of hexokinases
• Broad substrate specificity - hexokinases
can phosphorylate glucose, mannose and
fructose
• Isozymes - multiple forms of hexokinase occur
in mammalian tissues and yeast
• Hexokinases I, II, III are active at normal glucose
concentrations
• Hexokinase IV (Glucokinase) is active at higher glucose
levels, allows the liver to respond to large increases in
blood glucose
• Hexokinases I, II and III are allosterically inhibited by
physiological concentrations of their immediate product,
glucose-6-phosphate, but glucokinase is not.
 2. Glucose 6-Phosphate Isomerase
• Converts glucose 6-phosphate (G6P) (an aldose) to
fructose 6-phosphate (F6P) (a ketose)
• Enzyme preferentially binds the a-anomer of G6P
(converts to open chain form in the active site)
• Enzyme is highly stereospecific for G6P and F6P
• Isomerase reaction is near-equilibrium in cells
 3. Phosphofructokinase-1 (PFK-1)
• Catalyzes transfer of a phosphoryl group from ATP to the
C-1 hydroxyl group of F6P to form fructose 1,6-
bisphosphate (F1,6BP)
• PFK-1 is metabolically irreversible and a critical regulatory
point for glycolysis in most cells
• A second phosphofructokinase (PFK-2) synthesizes
fructose 2,6-bisphosphate (F2,6BP)
 4.
Aldolase
• Aldolase cleaves the hexose F1,6BP into two triose
phosphates: glyceraldehyde 3-phosphate (GAP)
and dihydroxyacetone phosphate (DHAP)
• Reaction is near-equilibrium, not a control point
 5. Triose Phosphate Isomerase (TPI)
• Conversion of DHAP into GAP
• Reaction is very fast, only the D-isomer of GAP is formed
• Reaction is reversible. At equilibrium, 96% of the triose
phosphate is DHAP. However, the reaction proceeds readily
from DHAP to GAP because the subsequent reactions of
glycolysis remove this product.
Fate of carbon atoms from hexose stage
to triose stage
 6. Glyceraldehyde 3-Phosphate
Dehydrogenase (GAPDH)
• Conversion of GAP to 1,3-bisphosphoglycerate
(1,3BPG)
• Molecule of NAD+ is reduced to NADH
• Energy from oxidation of GAP is conserved in acid-
anhydride linkage of 1,3BPG
• Next step of glycolysis uses the high-energy phosphate
of 1,3BPG to form ATP from ADP
 7. Phosphoglycerate Kinase (PGK)
• Transfer of phosphoryl group from the energy-rich mixed
anhydride 1,3BPG to ADP yields ATP and
3-phosphoglycerate (3PG)
• Substrate-level phosphorylation - Steps 6 and 7
couple oxidation of an aldehyde to a carboxylic acid
with the phosphorylation of ADP to ATP
 8. Phosphoglycerate Mutase
• Catalyzes transfer of a phosphoryl group from one part
of a substrate molecule to another
• Reaction occurs without input of ATP energy
 9. Enolase: 2PG to PEP
• 2-Phosphoglycerate (2PG) is dehydrated to
phosphoenolpyruvate (PEP)
• Elimination of water from C-2 and C-3 yields the enol-
phosphate PEP
• PEP has a very high phosphoryl group transfer potential
because it exists in its unstable enol form
 10. Pyruvate Kinase (PK)
PEP + ADP  Pyruvate + ATP

• Catalyzes a substrate-level
phosphorylation
• Metabolically irreversible
reaction
• Regulation both by
allosteric modulators and by
covalent modification
• Pyruvate kinase gene can be
regulated by various
hormones and nutrients
 Net reaction of glycolysis

During the convertion of glucose to pyruvate:

• Two molecules of ATP are produced
• Two molecules of NAD+ are reduced to NADH

Glucose + 2 ADP + 2 NAD+ + 2 Pi

2 Pyruvate + 2 ATP + 2 NADH + 2 H+ + 2 H2O

Scientific investigations
into fermentation of
grape sugar were
GLYCOLYSIS
pioneering studies
of glycolysis
 The Fate of Pyruvate
The sequence of reactions from glucose to pyruvate is
similar in most organisms and most types of cells.

The fate of pyruvate is variable.

Three reactions of pyruvate are of prime importance:

1. Aerobic conditions:
oxidation to acetyl CoA
which enters the citric acid
cycle for further oxidation
2. Anaerobic conditions
(muscles, red blood cells):
conversion to lactate
3. Anaerobic conditions
(microorganisms, yeast):
conversion to ethanol
 Diverse
Fates of
Pyruvate
 Metabolism of Pyruvate to Ethanol
Ethanol is formed from pyruvate in yeast and several other
microorganisms in anaerobic conditions.
Two reactions required:
The first step is the decarboxylation of pyruvate to
acetaldehyde.
Enzyme - pyruvate decarboxylase.
Coenzyme - thiamine pyrophosphate (derivative of the vitamin
thiamine B1)
The second step is the reduction of acetaldehyde to
ethanol. Enzyme - alcohol dehydrogenase (active site
contains a zinc). Coenzyme – NADH.
The conversion of glucose into ethanol is an example of alcoholic
fermentation.
The net result of alcoholic fermentation is:
Glucose+2Pi + 2ADP + 2H+  2 ethanol + 2CO2 + 2ATP + 2H2O

The ethanol formed in alcoholic fermentation provides a key

ingredient for brewing and winemaking.
There is no net NADH formation in the conversion of glucose
into ethanol.
NADH generated by the oxidation of glyceraldehyde 3-phosphate
is consumed in the reduction of acetaldehyde to ethanol.
 Metabolism of Pyruvate to Lactate
Lactate is formed from pyruvate in an animal organism
and in a variety of microorganisms in anaerobic
conditions.
The conversion of glucose into lactate is called lactic
acid fermentation.
Enzyme - lactate dehydrogenase.
Coenzyme – NADH.
• Muscles of higher organisms and humans lack pyruvate
decarboxylase and cannot produce ethanol from
pyruvate
• Muscle contain lactate dehydrogenase. During intense
activity when the amount of oxygen is limiting the lactic
acid can be accumulated in muscles (lactic acidosis).
• Lactate formed in skeletal muscles during exercise is
transported to the liver.
• Liver lactate dehydrogenase can reconvert lactate to
pyruvate.
Overall reaction in the conversion of glucose into lactate:
Glucose + 2 Pi + 2 ADP  2 lactate + 2 ATP + 2 H2O
As in alcoholic fermentation, there is no net NADH
formation.
NADH formed in the oxidation of glyceraldehyde 3-
phosphate is consumed in the reduction of
 Metabolism of Pyruvate to Acetyl CoA
In aerobic conditions pyruvate is converted to acetyl coenzyme A (acetyl CoA).
Acetyl CoA enters citric acid cycle where degrades to CO2 and H2O and the
energy released during such oxidation is utilized in NADH and FADH2.

Pyruvate is converted to acetyl CoA in the matrix of mitochondria.

The overall reaction: Pyruvate + NAD+ + CoA  acetyl CoA + CO2 +
NADH

Reaction is catalyzed by the pyruvate dehydrogenase complex (three

enzymes and five coenzymes).
If pyruvate is converted to acetyl CoA, NADH formed in the oxidation of
glyceraldehyde 3-phosphate ultimately transfers its electrons to O2 through
the electron-transport chain in mitochondria.
Other Sugars Can Enter Glycolysis
• Glucose is the main metabolic
fuel in most organisms
• Other sugars convert to
glycolytic
intermediates
• Fructose and sucrose (contains
fructose) are major
sweeteners in many foods and
beverages
• Galactose from milk lactose
(a disaccharide)
• Mannose from dietary
 The Entry of Fructose into Glycolysis
Much of the ingested fructose is metabolized by the liver, using
the fructose 1-phosphate pathway.

The first step is the phosphorylation of fructose to fructose 1-

phosphate by fructokinase.

Fructose 1-phosphate is then

split into glyceraldehyde and
dihydroxyacetone phosphate, an
intermediate in glycolysis, by a
specific fructose 1 -phosphate
aldolase.

Glyceraldehyde is then
phosphorylated to glyceraldehyde
3-phosphate, a glycolytic
intermediate, by triose kinase.
Fructose Is Converted to Glyceraldehyde 3-Phosphate
 Fructose can be phosphorylated to fructose 6-phosphate by
hexokinase.

However, the affinity of hexokinase for glucose is 20 times

as great as it is for fructose.

 Little fructose 6-phosphate is formed in the liver because

glucose is so much more abundant in this organ.

 Glucose, as the preferred fuel, is also trapped in the muscle

by the hexokinase reaction.

Because liver and muscle phosphorylate glucose rather than

fructose, adipose tissue is exposed to more fructose than
glucose.

Hence, the formation of fructose 6-phosphate in the adipose

tissue is not competitively inhibited to a biologically significant
extent, and most of the fructose in adipose tissue is
metabolized through fructose 6-phosphate.
 The Entry of Galactose into Glycolysis
Galactose is converted into glucose 6-phosphate in
four steps.

The first reaction is the phosphorylation of galactose

to
galactose 1-phosphate by galactokinase.
Galactose 1-phosphate react with
uridine diphosphate glucose (UDP-
glucose).

UDP-galactose and glucose 1-phosphate

are formed.

Enzyme - galactose 1-phosphate uridyl

transferase.

The galactose moiety of UDP-galactose is

then epimerized to glucose.

The configuration of the hydroxyl group at carbon 4

is inverted by UDP-galactose 4-epimerase.
Glucose 1-phosphate, formed from galactose, is
isomerized to glucose 6-phosphate by
phosphoglucomutase.
 The Entry of Mannose into Glycolysis
Mannose is converted to Fructose 6-Phosphate in two
steps.
Hexokinase catalyzes the convertion of mannose into
mannose 6-phosphate.

Isomerase converts mannose 6-phosphate into

fructose 6-phosphate (metabolite of glycolysis).
 Intolerance to Milk
Many people are unable to metabolize the
milk sugar lactose and experience
gastro- intestinal disturbances if they
drink milk.

Lactose intolerance, or hypolactasia, is caused by a deficiency of the

enzyme lactase, which cleaves lactose into glucose and galactose.
Microorganisms in the colon ferment undigested lactose to lactic acid
generating methane (CH4) and hydrogen gas (H2). The gas produced
creates the uncomfortable feeling of gut distention and the annoying
problem of flatulence.
The lactic acid is osmotically active and draws water into the intestine,
as does any undigested lactose, resulting in diarrhea.
The gas and diarrhea hinder the absorption of other nutrients (fats
and proteins).
Treatment:
-
to avoid the products containing lactose;
 Galactosemia
The disruption of galactose metabolism is referred to as
galactosemia.
Classic galactosemia is an inherited deficiency in galactose
1-phosphate uridyl transferase activity.

Symptoms:
- vomiting, diarrhea after consuming milk,
-
enlargement of the liver, jaundice,
sometimes cirrhosis,
- cataracts,
-
lethargy and retarded mental development,
- markedly
elevated blood-galactose level
The absence of the
-trgaalnascftoesreaissefoiunndred blood
cells is a
ni dethfeinuitriinvee.diagnostic criterion.
The most common treatment is to remove galactose (and
 Regulation of Glycolysis
The rate glycolysis is regulated to meet two major cellular needs:
(1) the production of ATP, and
(2) the provision of building blocks for synthetic reactions.

There are three control sites in glycolysis - the reactions catalyzed by

 hexokinase,
 phosphofructokinase 1, and
 pyruvate kinase
These reactions are irreversible.

Their activities are regulated

 by the reversible binding of allosteric effectors
 by covalent modification
 by the regulation of transcription (change of the enzymes amounts).

The time required for allosteric control, regulation by phosphorylation,

and transcriptional control is typically in milliseconds, seconds, and
hours, respectively.
 Phosphofructokinase 1 Is the Key Enzyme in
the Control of Glycolysis
Phosphofructokinase 1 is the most important control element in
the mammalian glycolytic pathway.

Phosphofructokinase 1
in the liver is a tetramer
of four identical
subunits.
The positions of the
catalytic and allosteric
sites are identical.
High levels of ATP allosterically inhibit the
phosphofructokinase 1 in the liver lowering its affinity for
fructose 6-phosphate.
AMP reverses the inhibitory action of ATP, and so the
activity of the enzyme increases when the ATP/AMP ratio
is lowered (glycolysis is stimulated as the energy charge
falls).
A fall in pH also inhibits phosphofructokinase 1 activity.
The inhibition of phosphofructokinase by H+ prevents
excessive formation of lactic acid and a precipitous drop in
blood pH (acidosis).
Phosphofructokinase 1 is inhibited by citrate, an
early intermediate in the citric acid cycle.
A high level of citrate means that biosynthetic precursors are
abundant and additional glucose should not be degraded for this
purpose.
Fructose 2,6-bisphosphate (F-2,6-BP) is a
potent activator of phosphofructokinase
1.
F-2,6-BP activates phosphofructokinase I by
increasing its affinity for fructose 6-phosphate
and diminishing the inhibitory effect of ATP.

Fructose 2,6-bisphosphate is formed in a reaction catalyzed by

phosphofructokinase 2 (PFK2), a different enzyme from
phosphofructokinase 1.
Fructose 2,6-bisphosphate
is hydrolyzed to fructose 6-
phosphate by a specific
phosphatase, fructose
bisphosphatase 2 (FBPase2).

Both PFK2 and FBPase2 are

present in a single
polypeptide chain
(bifunctional enzyme).
 Regulation of Glycolysis by Fructose 2,6-bisphosphate
When blood glucose
level is low the glucagon
is synthesized by
pancreas
Glucagon binds to cell
receptors, stimulates
the protein kinase A
activity
Protein kinase A
phosphorylates the
PFK-2 inhibiting its
kinase activity and
stimulating its
phosphatase activity
As result the amount
of F-2,6-BP is
decre- ased and
glycolysis is slowed.
Regulation of Hexokinase

Hexokinase is inhibited by its

product, glucose 6-
phosphate (G-6-P).

High concentrations of G-6-P signal that the cell no longer

requires glucose for energy, for glycogen, or as a source of
biosynthetic precursors.

Glucose 6-phosphate levels increase when glycolysis is inhibited at

sites further along in the pathway.

Glucose 6-phosphate inhibits hexokinase isozymes I, II and III.

Glucokinase (isozyme IV) is not inhibited by glucose 6-phosphate.

The role of glucokinase is to provide glucose 6-phosphate for the
synthesis of glycogen.
 Regulation of Pyruvate Kinase (PK)
Several isozymic
forms of pyruvate
kinase are present in
mammals (the L type
predominates in
liver, and the M
type in muscle and
brain).

Fructose 1,6-
bisphosphate
allosterically
activates pyruvate
kinase.

ATP allosterically inhibits pyruvate kinase to slow

glycolysis when the energy charge is high.
The isozymic forms of pyruvate kinase differ in their
susceptibility to covalent modification.
The catalytic properties of the L (liver) form—but not of the
M (brain) form controlled by reversible phosphorylation.

When the
blood-glucose
level is low, the
glucagon leads
to the
phosphoryla-
tion of
pyruvate
kinase, which
diminishes its
activity.
 Regulation of
Inhibition
1)PFK-1 is Glycolysis
inhibited by ATP
and citrate
2)Pyruvate
kinase is
inhibited by ATP
and alanine
3)Hexokinase is
inhibited by
excess glucose
6-phosphate

Stimulation
1)AMP and fructose 2,6-
bisphosphate (F2,6BP) relieve
the inhibition of PFK-1 by
ATP

2)F1,6BP stimulate the activity

of pyruvate kinase Alanine
 Regulation of Hexose Transporters
Several glucose transporters (GluT) mediate the thermodynamically downhill
movement of glucose across the plasma membranes of animal cells.

GluT is a family of 5 hexose transporters.

Each member of this protein family consists of a single polypeptide chain
forming 12 transmembrane segments.

GLUT1 and GLUT3,

present in erythrocytes,
endothelial, neuronal
and some others
mammalian cells, are
responsible for basal
glucose uptake. Their Km
value for glucose is about
1 mM.
GLUT1 and GLUT3
continually transport
glucose into cells at an
essentially constant rate.
GLUT2, present in liver and pancreatic -cells has a
very high Km value for glucose (15-20 mM).

Glucose enters these tissues at a biologically significant

rate only when there is much glucose in the blood.

GLUT4, which has a Km value of 5 mM, transports glucose

into muscle and fat cells.
The presence of insulin leads to a rapid increase in the
number of GLUT4 transporters in the plasma membrane.
Insulin promotes the uptake of glucose by muscle and
fat. The amount of this transporter present in muscle
membranes increases in response to endurance exercise
training.

GLUT5, present in the small intestine, functions

primarily as a fructose transporter.
 The Pasteur Effect

 Under anaerobic conditions

the conversion of glucose to
pyruvate is much higher
than under aerobic
conditions (yeast cells
produce more ethanol and
muscle cells accumulate
lactate)

 The Pasteur Effect is the

slowing of glycolysis in the
presence of oxygen.

• More ATP is produced under aerobic conditions than

under anaerobic conditions, therefore less glucose
is consumed aerobically.
The Pentose Phosphate Pathway
 The fate of glucose molecule in the cell

Synthesis of
glycogen
Glucose
Pentose phosphate
pathway

Glucose-6- Ribose,
Glycogen
NADPH
phosphate

Degradation of
glycogen

Gluconeogenesis
Glycolysi
s

Pyruvate
 The Role of Pentose Phosphate
Pathway (phosphogluconate pathway)

(1)Synthesis of NADPH (for reductive reactions in

biosynthesis of fatty acids and steroids)
(2)Synthesis of Ribose 5-phosphate (for the
biosynthesis of ribonucleotides (RNA, DNA) and several
cofactors)
(3)Pentose phosphate pathway also provides a means
for the metabolism of “unusual sugars”, 4, 5 and 7
carbons.
Pentose phosphate pathway does not function in
the
production of high energy compounds like ATP.
 Occurrence of the pentose phosphate pathway
• Liver, mammary and adrenal glands, and adipose tissue
• Red blood cells (NADPH maintains reduced iron)
• NOT present in skeletal muscles.
• All enzymes in the cycle occur in the cytosol
Two phases:
1)The oxidative
phase that
generates
NADPH
2)The
nonoxidative
phase
(transketolase/
transaldolase
system) that
interconvert
phosphorylated
sugars.
Oxidative
phase of
pentose
phosphate
cycle
Nonoxidative
phase of
pentose
phosphate
cycle
Conversion of glucose-6-phosphate to
6-phosphogluconolactone
Conversion of 6-phosphogluconolactone to
6-phosphogluconate
Conversion of 6-phosphogluconate to ribuloso
5-phosphate
Conversions of ribulose 5-phosphate

Ribose 5-phosphate
isomerase
The pentose phosphate pathway ends with these five
reactions in some tissue.
In others it continue in nonoxidative mode to make
fructose 6-phosphate and glyceraldehyde 3-phosphate.
These reactions link pentose phosphate pathway with
glycolysis.

The net reaction for the pentose

phosphate pathway
Glucose + ATP + 2NADP+ + H2O
ribose 5-phosphate + CO2 + 2NADPH + 2H+ + ADP
 Interconversions Catalyzed by
Transketolase and Transaldolase

• Transketolase and transaldolase have

broad substrate specificities
• They catalyze the exchange of two-
and three-carbon fragments
between sugar phosphates
• For both enzymes, one substrate is an
aldose, one substrate is a ketose
Reaction catalyzed by transketolase
Reaction catalized by transaldolase
Reaction catalyzed by transketolase
 Glucose-6-phosphate dehydrogenase
deficiency
NADPH is required for the proper
action of the tripeptide
glutathione (GSH) (maintains it in
the reduced state).

GSH in erythrocytes maintains

hemoglobin in the reduced Fe(II)
state necessary for oxygen binding.

GSH also functions to eliminate

H2O2 and organic peroxides.
Peroxides can cause irreversible
damage to hemoglobin and destroy
cell membranes.
Glucose-6-phosphate dehydrogenase deficiency – the most
common enzymopathy affecting hundreds of millions of people.
About 10 % of individuals of African or Mediterranean
descent have such genetic deficiency.
Erythrocytes with a
lowered level of reduced
glutathione are more
susceptible to hemolysis
and are easily destroyed
especially if they are
stressed with drugs
(for example,
antimalarial drugs).

In severe cases, the

massive destruction of
Red blood cells with Heinz bodies.
red blood cells causes
Dark particles (Heinz bodies) are denaturated
death. proteins adhered to cell membranes.