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METABOLISM OF CARBOHYDRATES: GLYCOLYSIS

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Title: METABOLISM OF CARBOHYDRATES: GLYCOLYSIS


1
METABOLISM OF CARBOHYDRATES GLYCOLYSIS
For centuries, bakeries and breweries have
exploited the conversion of glucose to ethanol
and CO2 by glycolysis in yeast
2
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.
3
?-amilase hydrolyzes the ?-1-4-glycosidic bonds
randomly to produce smaller subunits like
maltose, dextrines and unbranched
oligosaccharides.
4
The intestinal juice contains enzymes hydrolyzing
disaccharides into monosaccharides (they are
produced in the intestinal wall) Sucrase
hydrolyses sucrose into glucose and fructose
Glucose
Fructose
Sucrose
5
Glucose
Galactose
Lactase hydrolyses lactose into glucose and
galactose
Lactose
Glucose
Glucose
Maltase hydrolyses maltose into two glucose
molecules
6
ABSORPTION OF CARBOHYDRATES
Only monosaccharides are absorbed
The rate of absorption galactose gt glucose gt
fructose
Glucose and galactose from the intestine into
endothelial cells are absorbed by secondary
active transport
Protein
7
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.

8
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
GluT4 - in muscles and fat cells.
9
The fate of glucose molecule in the cell
Glucose
Pentose phosphate pathway supplies the NADPH for
lipid synthesis and pentoses for nucleic acid
synthesis
Glycogenogenesis (synthesis of glycogen) is
activated in well fed, resting state
Glucose-6-phosphate
Ribose, NADPH
Glycogen
Pyruvate
Glycolysis is activated if energy is
required
10
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.
11
  • 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

12
  • Catabolism of glucose in aerobic conditions via
    glycolysis and the citric acid cycle

13
The glycolytic pathway consist of ten
enzyme-catalyzed reactions that begin with a
glucose and split it into two molecules of
pyruvate
14
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 glucose

15
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.
16
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.
17
In stage 3, ATP is harvested when the
three-carbon fragments are oxidized to pyruvate.
18
1. Hexokinase
Glycolysis Has 10 Enzyme-Catalyzed Steps
  • Each chemical reaction prepares a substrate for
    the next step in the process
  • Transfers the g-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

19
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.

20
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

21
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)

22
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

23
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.

24
Fate of carbon atoms from hexose stage to triose
stage
25
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

26
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

27
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

28
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

29
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

30
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
31
Scientific investigations into fermentation of
grape sugar were pioneering studies of
glycolysis
GLYCOLYSIS
32
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
33
Diverse Fates of Pyruvate
34
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.
35
The conversion of glucose into ethanol is an
example of alcoholic fermentation. The net
result of alcoholic fermentation is Glucose2Pi
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.

36
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.
37
  • 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
    pyruvate.

38
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.
39
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 polysaccharides,
    glycoproteins

40
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.
41
Fructose Is Converted to Glyceraldehyde
3-Phosphate
42
  • 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.

43
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.
44
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.
45
(No Transcript)
46
Glucose 1-phosphate, formed from galactose, is
isomerized to glucose 6-phosphate by
phosphoglucomutase.
47
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).
48
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
- the enzyme lactase can be
ingested.
49
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

- galactose is found in the urine.
The absence of the transferase in red blood cells
is a definitive diagnostic criterion. The most
common treatment is to remove galactose (and
lactose) from the diet.
50
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.

51
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.
52
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.
53
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).
54
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.

55
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.
56
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.
Finally, alanine (synthesized in one step from
pyruvate) also allosterically inhibits the
pyruvate kinases (signal that building blocks are
abundant).
57
The isozymic forms of pyruvate kinase differ in
their susceptibility to covalent modification.
The catalytic properties of the L (liver)
formbut 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.
58
Regulation of Glycolysis
Inhibition 1) PFK-1 is 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
59
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.
60
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.
61
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.

62
The Pentose Phosphate Pathway
63
The fate of glucose molecule in the cell
Synthesis of glycogen
Glucose
Pentose phosphate pathway
Glucose-6-phosphate
Ribose, NADPH
Glycogen
Degradation of glycogen
Gluconeogenesis
Glycolysis
Pyruvate
64
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.
65
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

66
Two phases 1) The oxidative phase that
generates NADPH 2) The nonoxidative phase
(transketolase/ transaldolase system) that
interconvert phosphorylated sugars.
67
Oxidative phase of pentose phosphate cycle
68
Nonoxidative phase of pentose phosphate cycle
69
Conversion of glucose-6-phosphate to
6-phosphogluconolactone
70
Conversion of 6-phosphogluconolactone to
6-phosphogluconate
71
Conversion of 6-phosphogluconate to ribuloso
5-phosphate
72
Conversions of ribulose 5-phosphate
Ribose 5-phosphate isomerase
73
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
74
Interconversions Catalyzed byTransketolase 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

75
Reaction catalyzed by transketolase
76
Reaction catalized by transaldolase
77
Reaction catalyzed by transketolase
78
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.
79
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 causes death.
Red blood cells with Heinz bodies. Dark
particles (Heinz bodies) are denaturated proteins
adhered to cell membranes.
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