Molecular Biochemistry

The Pentose Phosphate Pathway – PPP

And other ways of Hexose Metabolism
 Overview

 It is an alternate route for the oxidation

of glucose without direct consumption
or generation of ATP.

 It takes place entirely in the cytoplasm.

 Overview
 NADPH production
Glutathione reduction (cellular antioxidant), Synthetic pathways (fatty acid/cholesterol synthesis)

 Glycolytic intermediates
Fructose-6-phosphate, glyceraldehyde-3-phosphate

 Ribose-5-phosphate
Nucleotide synthesis
 Pentose Phosphate Pathway
 The pentose phosphate pathway is an alternative route for the
metabolism of glucose.
 is a more complex pathway than glycolysis

 It does not lead to formation of ATP but has two major functions:
 (1) the formation of NADPH for synthesis of fatty acids and steroids, and
maintaining reduced glutathione for antioxidant activity,
 (2) the synthesis of ribose for nucleotide and nucleic acid formation.

 Glucose, fructose, and galactose are the main hexoses absorbed from the
gastrointestinal tract, derived from dietary starch, sucrose, and lactose,
respectively.
 Fructose and galactose can be converted to glucose, mainly in the liver.
 Importance of pentose phosphate pathway :
 Generation of NADPH
- mainly used for reductive synthesis of
fatty acids, cholesterol and steroid
hormones.
- hydroxylation reaction in metabolism
of phenylalanine and tryptophan.
- production of reduced glutathione in
erythrocytes and other cells.

 Production of ribose residues

1. used for nucleotide,
2. nucleic acid,
3. and coenzyme biosynthesis

 Serves as an entry into Glycolysis for

both 5‐carbon & 6‐carbon sugars.
 Pentose Phosphate Pathway
 The pentose phosphate pathway (also called the hexose monophosphate Shunt,
hexose monophosphate pathway HMP, or 6-phosphogluconate pathway) occurs in
the cytosol of the cell.
1. It includes two, irreversible oxidative reactions,
2. followed by a series of reversible sugar–phosphate interconversions.

 No ATP is directly consumed or produced in the cycle.

 Carbon 1 of glucose 6-phosphate is released as CO2, and two NADPH are produced
for each glucose 6-phosphate molecule entering the oxidative part of the pathway.
 The rate and direction of the reversible reactions of the pentose phosphate pathway
are determined by the supply of and demand for intermediates of the cycle.

 The pathway provides a major portion of the body’s NADPH, which functions as a
biochemical reductant.

 It also produces ribose 5-phosphate, required for the biosynthesis of nucleotides and
provides a mechanism for the metabolic use of five-carbon sugars obtained from the
diet or the degradation of structural carbohydrates in the body.
 Uses of NADPH
 The oxidative portion of the pentose phosphate pathway
consists of three reactions that lead to the formation of ribulose
5-phosphate, CO2, and two molecules of NADPH for each
molecule of glucose 6-phosphate oxidized.

1. This portion of the pathway is particularly important in the

liver, lactating mammary glands, and adipose, which are active
in the NADPH-dependent biosynthesis of fatty acids and
2. in the testes, ovaries, placenta and adrenal cortex, which are
active in the NADPH-dependent biosynthesis of steroid
hormones and in
3. erythrocytes, which require NADPH to keep glutathione
reduced.
 REACTIONS OF THE PENTOSE
PHOSPHATE PATHWAY OCCUR IN THE CYTOSOL
 Like glycolysis, the enzymes of the pentose phosphate pathway are cytosolic.
 Unlike glycolysis, oxidation is achieved by dehydrogenation using NADP+, not
NAD+, as the hydrogen acceptor.

 The sequence of reactions of the pathway may be divided into two phases:
1. an irreversible oxidative phase and
2. a reversible nonoxidative phase.

 In the first phase, glucose-6-phosphate undergoes dehydrogenation and

decarboxylation to yield a pentose, ribulose-5-phosphate.
 In the second phase, ribulose-5-phosphate is converted back to glucose-6-
phosphate by a series of reactions involving mainly two enzymes: transketolase
& transaldolase.
 1st reaction of PPP
 1. Dehydrogenation of glucose 6-phosphate:
 Glucose 6-phosphate dehydrogenase (G6PD) catalyzes an irreversible
oxidation of glucose 6-phosphate to 6-phosphogluconolactone in a
reaction that is specific for NADP+ as its coenzyme.
 The pentose phosphate pathway is regulated primarily at the G6PD
reaction.
 NADPH is a potent competitive inhibitor of the enzyme, and, under
most metabolic conditions, the ratio of NADPH/NADP+ is
sufficiently high to inhibit enzyme activity. However, with increased
demand for NADPH, the ratio of NADPH/NADP+ decreases and flux
through the cycle increases in response to the enhanced activity of
G6PD.
 Insulin upregulates expression of the gene for G6PD, and flux
through the pathway increases in the well-fed state.
 Pentose Phosphate Pathway
 The linear part of the pathway carries out oxidation and
decarboxylation of the 6-C sugar glucose-6-P, producing the 5-C
sugar ribulose-5-P.
 6-Phosphogluconolactonase catalyzes hydrolysis of the ester
linkage, resulting in ring opening.
 The product is 6-phosphogluconate.

G lucose-6-phosphate 6-Phospho- O O
D ehydrogenase glucono- 1C
6 CH O PO 2 6 CH O PO 2 lactonase
2 3 + 2 3
N AD P H + H HC OH
H
5 O O H NADP
+
H
5 O H 2O H+ 2
H H HO 3CH
4 OH H 1 4
OH H O
1 HC OH
4
OH H OH
3 2 3 2 HC OH
5
H OH H OH CH 2 O PO 3 2
6
glucose-6-phosphate 6-phoshogluconolactone 6-phosphogluconate

NADP+ serves as electron acceptor.

 Formation of ribulose 5-phosphate
 6-Phosphogluconolactone is hydrolyzed by 6-phosphogluconolactone
hydrolase. (or gluconolactone hydrolase.)
 The reaction is irreversible and not rate-limiting.

 The oxidative decarboxylation of the product, 6-phosphogluconate is

catalyzed by 6-phosphogluconate dehydrogenase, which also requires
NADP+ as hydrogen acceptor.

 This irreversible reaction produces :

1. a pentose sugar–phosphate (ribulose 5-phosphate), Ketopentose (by
decarboxylation)
2. CO2 (from carbon 1 of glucose), and
3. a second molecule of NADPH .
 O O Phosphogluconate
1C Dehydrogenase
HC OH 1CH 2 OH
2 NADP + NADPH + H +
HO 3CH C O
2
HC OH HC OH
4 3
HC OH CO 2 HC OH
5 4
CH 2 OPO 3 2 CH 2 OPO 3 2
6 5
6-phosphogluconate ribulose-5-phosphate

 Phosphogluconate Dehydrogenase catalyzes oxidative

decarboxylation of 6-phosphogluconate, to yield the 5-C ketose:
ribulose-5-phosphate.

 Loss of the carboxyl at C1 as CO2.

 NADP+ serves as oxidant.
NADPH producing reactions
 Glucose-6-P dehydrogenase
 6-P-gluconate dehydrogenase
 Comparison of NADP and NAD.
 NADPH can be thought of as a high-energy molecule, much in the
same way as NADH.
 However, the electrons of NADPH are destined for use in reductive
biosynthesis, rather than for transfer to oxygen as is the case with
NADH.
 The coenzyme NADP+ differs from NAD+ only by the presence of a
phosphate group on one of the ribose units.
 This seemingly small change in structure allows NADP+ to interact
with NADP+- specific enzymes that have unique roles in the cell.

 For example, in the cytosol of hepatocytes the steady-state ratio of

NADP+/NADPH is approximately 0.1, which favors the use of NADPH
in reductive biosynthetic reactions.
 This contrasts with the high ratio of NAD+/NADH (approximately
1000), which favors an oxidative role for NAD+.
 NADPH & NADH
 NADPH, a product of the Pentose Phosphate Pathway, functions as a
reductant in anabolic (synthetic) pathways, e.g., fatty acid synthesis.
 NAD+ serves as electron acceptor in catabolic pathways, in which
metabolites are oxidized.
 The resultant NADH is reoxidized by the respiratory chain, producing
ATP.
 REVERSIBLE NONOXIDATIVE REACTIONS
 The nonoxidative reactions of the pentose phosphate pathway occur in
all cell types synthesizing nucleotides and nucleic acids.
 These reactions catalyze the interconversion of sugars containing three
to seven carbons.

 These reversible reactions permit ribulose 5-phosphate (produced by

the oxidative portion of the pathway)
1. to be converted either to ribose 5-phosphate (needed for nucleotide
synthesis,)
2. or to intermediates of glycolysis—fructose 6-phosphate and
glyceraldehyde 3-phosphate.

 Many cells that carry out reductive biosynthetic reactions have a

greater need for NADPH than for ribose 5-phosphate.
REVERSIBLE NONOXIDATIVE REACTIONS

 In this case, transketolase (which transfers two-carbon units in a thiamine

pyrophosphate (TPP)-requiring reaction)
 and transaldolase (which transfers three-carbon units)
 convert the ribulose 5-phosphate produced as an end-product of the
oxidative reactions to
 glyceraldehyde 3-phosphate and fructose 6-phosphate, which are
intermediates of glycolysis.

 In contrast,
 under conditions in which the demand for ribose for incorporation into
nucleotides and nucleic acids is greater than the need for NADPH,
 the nonoxidative reactions can provide the biosynthesis of ribose 5-
phosphate from glyceraldehyde 3-phosphate and fructose 6-phosphate in
the absence of the oxidative steps.
 The Nonoxidative Phase Generates Ribose Precursors
 Ribulose-5-phosphate is the substrate for two enzymes.
 Ribulose-5-phosphate 3-epimerase alters the configuration about carbon 3, forming the
epimer xylulose 5-phosphate, also a ketopentose.

 Ribose-5-phosphate keto-isomerase converts ribulose 5-phosphate to the corresponding

aldopentose, ribose-5-phosphate, which is used for nucleotide and nucleic acid synthesis.

CH 2OH

C O
Epimerase
HO C H
• Epimerase interconverts stereoisomers CH 2OH H C OH
ribulose-5-P and xylulose-5-P. CH 2OPO 32
C O
• Isomerase converts the ketose ribulose-5-P xylulose-5-
H C OH phosphate
to the aldose ribose-5-P.
H C OH HC O
• Both reactions are reversible.
CH 2OPO 32 H C OH
ribulose-5- H C OH
phosphate Isomerase
H C OH

CH 2OPO 32
ribose-5-
phosphate
 Phase 2 Reactions:
 Transketolase transfers the two-carbon units
 The reaction requires Mg2+ and thiamin diphosphate (vitamin
B1) as coenzyme.

 Transketolase catalyzes the transfer of the two-carbon unit

from xylulose-5-phosphate to ribose-5-phosphate, producing
the seven-carbon ketose sedoheptulose-7-phosphate and the
aldose glyceraldehyde-3-phosphate.
 These two products then undergo transaldolation.

 Transaldolase catalyzes the transfer of a three carbon moiety

(carbons 1–3) from the ketose sedoheptulose-7-phosphate
onto the aldose glyceraldehyde-3-phosphate to form the
ketose fructose 6-phosphate and the four-carbon aldose
erythrose 4-phosphate.
 CH 2 O H
T ra n s k e to la s e
C O

CH 2 O H HC O HO C H

C O H C OH H C OH

HO C H H C OH HC O H C OH

H C OH
+ H C OH H C OH
+ H C OH

CH 2 O P O 3 2  CH 2 O P O 3 2  CH 2 O P O 3 2  CH 2 O P O 3 2 

x y lu lo s e - r ib o s e - g ly c e r a ld e h y d e - s e d o h e p tu lo s e -
5 -p h o s p h a te 5 -p h o s p h a te 3 -p h o s p h a te 7 -p h o s p h a te

 Transketolase transfers a 2-C fragment from xylulose-5-P to either

ribose-5-P or erythrose-4-P.
 Transketolase utilizes as prosthetic group thiamine pyrophosphate
(TPP), a derivative of vitamin B1.
(Pyruvate Dehydrogenase of Krebs Cycle also utilizes TPP as coenzyme.)

 Transfer of the 2-C fragment to the 5-C aldose ribose-5-phosphate yields

sedoheptulose-7-phosphate.
 Transfer of the 2-C fragment instead to the 4-C aldose erythrose-4-
phosphate yields fructose-6-phosphate.
 C H 2O H
T ra n sa ld o la s e
C O H 2C OH

HO CH C O

HC OH HC O HO CH

HC OH HC O HC OH HC OH

HC OH + HC OH HC OH + HC OH
2 2 2 2
H 2C O PO 3 H 2C O PO 3 H 2C O PO 3 H 2C O PO 3

s e d o h e p tu lo s e - g ly c e ra ld e h y d e - e ry th ro s e - fru c to s e -
7 -p h o s p h a te 3 -p h o s p h a te 4 -p h o s p h a te 6 -p h o s p h a te

Transaldolase catalyzes transfer of a 3-C

dihydroxyacetone moiety, from sedoheptulose-7-
phosphate to glyceraldehyde-3-phosphate.
The diagram at right (3) ribulose-5-P
summarizes flow of 15 C IS EP
atoms through Pentose ribose-5-P (2) xylulose-5-P
Phosphate Pathway
TK
reactions by which 5-C
sugars are converted to glyceraldehyde-3-P
3-C and 6-C sugars.
sedoheptulose 7 P

IS = Isomerase fructose-6- P TA
EP = Epimerase
erythrose-4-P
TK = Transketolase
TA = Transaldolase TK fructose-6-P
glyceraldehyde-3-P
 2 NADP+ 2 NADPH + CO2
glucose-6-P ribulose-5-P ribose-5-P

fructose-6-P, &
glyceraldehyde-3-P
Pentose Phosphate Pathway producing
maximum NADPH

 Glucose-6-phosphate may be regenerated from either the

3-C glyceraldehyde-3-phosphate or the 6-C fructose-6-
phosphate, via enzymes of Gluconeogenesis for reentry
to the linear portion of the Pentose Phosphate Pathway,
maximizing formation of NADPH.
 The Pentose Phosphate Pathway is divided into two phases

 Oxidative non-reversible phase

-generates NAPDH
-Glucose 6-p undergoes dehydrogenation and
decarboxylation to give a pentose, ribulose 5-p,
which is converted to its isomer, D-ribose 5-p.
-Overall equation of 1st phase:
Glucose 6-p + 2 NADP++ H2O  ribose 5-p + CO2 + 2
NADPH + 2 H+

 Non-oxidative reversible phase

-ribose 5‐P is converted back to Glucose 6-p by a
series of reactions involving especially two
enzymes
1. Transketolase :Transfer of the 2‐C fragment
2. Transaldolase :Transfer of the 3‐C fragment
Depending on needs of a cell for ribose-5-phosphate,
NADPH, and ATP, the Pentose Phosphate Pathway can
operate in various modes, to maximize different products.
There are three major scenarios:

2 NADP+ 2 NADPH + CO2

glucose-6-P ribulose-5-P ribose-5-P

Pentose Phosphate Pathway producing

NADPH and ribose-5-phosphate
 2 NADP+ 2 NADPH + CO2
glucose-6-P ribulose-5-P ribose-5-P

fructose-6-P, &
glyceraldehyde-3-P

to Glycolysis
for production of ATP
Pentose Phosphate Pathway producing
NADPH and ATP

Glyceraldehyde-3-P and fructose-6-P, formed from 5-C sugar

phosphates, may enter Glycolysis for ATP synthesis.
The pathway also produces NADPH.
 2 NADP+ 2 NADPH + CO2
glucose-6-P ribulose-5-P ribose-5-P

fructose-6-P, &
glyceraldehyde-3-P

to Glycolysis
for production of ATP
Pentose Phosphate Pathway producing
NADPH and ATP

 Ribose-1-phosphate generated during catabolism of

nucleosides also enters Glycolysis in this way, after first
being converted to ribose-5-phosphate.
 Thus the Pentose Phosphate Pathway serves as an entry
into Glycolysis for both 5-carbon & 6-carbon sugars. (!!!)
 Reduction of hydrogen peroxide
 Hydrogen peroxide is one of a family of reactive oxygen species (ROS)
that are formed from the partial reduction of molecular oxygen.
 These compounds are formed continuously as by-products of aerobic
metabolism, through reactions with drugs and environmental toxins, or
when the level of antioxidants is diminished, all creating the condition of
oxidative stress.

 The highly reactive oxygen intermediates can cause serious chemical

damage to DNA, proteins, and unsaturated lipids, and can lead to cell
death.
 These ROS have been implicated in a number of pathologic processes,
including reperfusion injury, cancer, inflammatory disease, and aging.
 The cell has several protective mechanisms that minimize the toxic
potential of these compounds.
 Enzymes that catalyze antioxidant reactions:
 Reduced glutathione, a tripeptide thiol - (γ-glutamylcysteinylglycine)
present in most cells, can chemically detoxify hydrogen peroxide.
 This reaction, catalyzed by the selenium-requiring glutathione peroxidase,
forms oxidized glutathione, which no longer has protective properties.
 The cell regenerates reduced glutathione in a reaction catalyzed by
glutathione reductase, using NADPH as a source of reducing equivalents. !!!
 Thus, NADPH indirectly provides electrons for the reduction of hydrogen
peroxide.

 Note: Erythrocytes are totally dependent on the pentose phosphate

pathway for their supply of NADPH because, unlike other cell types,
erythrocytes do not have an alternate source for this essential coenzyme.
 Additional enzymes, such as superoxide dismutase and catalase, catalyze the
conversion of other toxic oxygen intermediates to harmless products.

 As a group, these enzymes serve as a defense system to guard against the

toxic effects of reactive oxygen species.
 Antioxidant chemicals
 A number of intracellular reducing agents, such as ascorbate,
vitamin E and β-carotene are able to reduce and, thus, detoxify
oxygen intermediates in the laboratory.

 Consumption of foods rich in these antioxidant compounds has

been correlated with a reduced risk for certain types of cancers,
as well as decreased frequency of certain other chronic health
problems.

 However, clinical trials with antioxidants as dietary supplements

have failed to show clear beneficial effects.
 The Two Major Pathways for the Catabolism
of Glucose Have Little in Common
 Although glucose-6-phosphate is common to both pathways, the pentose
phosphate pathway is markedly different from glycolysis:

1. Oxidation utilizes NADP+ rather than NAD+, and

2. CO2, which is not produced in glycolysis, is a characteristic product.
3. No ATP is generated in the pentose phosphate pathway, whereas it is a product
of glycolysis.

 The two pathways are, however, connected.

 Xylulose 5-phosphate activates the protein phosphatase that dephosphorylates
the 6-phosphofructo-2-kinase/fructose 2,6-bisphophatase bifunctional enzyme.
 This activates the kinase and inactivates the phosphatase, leading to increased
formation of fructose 2,6-bisphosphate, -> increased activity of
phosphofructokinase-1, -> and hence increased glycolysis.
 INGESTION OF LARGE QUANTITIES OF FRUCTOSE
HAS PROFOUND METABOLIC CONSEQUENCES

 Diets high in sucrose or in high-fructose syrups (HFS) used in

manufactured foods and beverages lead to large amounts of fructose (and
glucose) entering the hepatic portal vein.
 Fructose undergoes more rapid glycolysis in the liver than does glucose
because it bypasses the regulatory step catalyzed by phosphofructokinase.

 This allows fructose to flood the pathways in the liver, leading to

increased fatty acid synthesis, esterification of fatty acids, and secretion of
VLDL, which may raise serum triacylglycerols and ultimately raise LDL
cholesterol concentrations.
 Fructokinase in liver, kidney, and intestine, catalyzes the
phosphorylation of fructose to fructose-1-phosphate.

 This enzyme does not act on glucose.

 Fructose
 Fructose-1-phosphate is cleaved to d-
glyceraldehyde and dihydroxyacetone
phosphate by aldolase B, an enzyme found in
the liver, which also functions in glycolysis in
the liver by cleaving fructose 1,6-bisphosphate.
 d-Glyceraldehyde enters glycolysis via
phosphorylation to glyceraldehyde-3-
phosphate catalyzed by triokinase.
 The two triose phosphates, dihydroxyacetone
phosphate, and glyceraldehyde-3-phosphate,
1. may either be degraded by glycolysis
2. or may be substrates for aldolase and hence
gluconeogenesis, which is the fate of much of
the fructose metabolized in the liver.

 In extrahepatic tissues, hexokinase catalyzes

the phosphorylation of most hexose sugars,
including fructose, but
 glucose inhibits the phosphorylation of fructose
since it is a better substrate for hexokinase.
 GALACTOSE IS NEEDED FOR
THE SYNTHESIS OF LACTOSE, GLYCOLIPIDS, PROTEOGLYCANS, &
GLYCOPROTEINS
 Galactose is derived from intestinal hydrolysis of the disaccharide lactose, the sugar
found in milk.
 It is readily converted in the liver to glucose.
 Galactokinase catalyzes the phosphorylation of galactose, using ATP as phosphate donor.
 Galactose 1-phosphate reacts with UDPGlc to form uridine diphosphate galactose
(UDPGal) and glucose 1-phosphate, in a reaction catalyzed by galactose-1-phosphate
uridyl transferase.
 The conversion of UDPGal to UDPGlc is catalyzed by UDPGal 4-epimerase.
 The reaction involves oxidation, and then reduction, at carbon 4, with NAD+ as a
coenzyme.
 The UDPGlc is then incorporated into glycogen.
 The epimerase reaction is freely reversible, so glucose can be converted to galactose, and
galactose is not a dietary essential.
 Galactose is required in the body not only for the formation of lactose in lactation, but
also as a constituent of glycolipids (cerebrosides), proteoglycans, and glycoproteins.
 In the synthesis of lactose in the mammary gland, UDPGal condenses with glucose to
yield lactose, catalyzed by lactose synthase.
 Regulation of Glucose-6-phosphate Dehydrogenase:

 Glucose-6-phosphate Dehydrogenase is the committed step

of the Pentose Phosphate Pathway.
This enzyme is regulated by availability of the substrate
NADP+.
 As NADPH is utilized in reductive synthetic pathways, the
increasing concentration of NADP+ stimulates the Pentose
Phosphate Pathway, to replenish NADPH.
 Glucose-6-Phosphate Dehydrogenase Deficiency
 Glucose 6-phosphate dehydrogenase (G6PD) deficiency is an inherited disease
characterized by hemolytic anemia caused by the inability to detoxify oxidizing agents.
 G6PD deficiency is the most common disease-producing enzyme abnormality in humans,
affecting more than 400 million individuals worldwide.
 This deficiency has the highest prevalence in the Middle East, tropical Africa and Asia,
and parts of the Mediterranean.
 The gene is on the X chromosome, so it is mainly males who are affected.
 Some 400 million people carry a mutated gene for glucose-6-phosphate
dehydrogenase, making it the most common genetic defect, but most are
asymptomatic.
 This negative effect of G6PD deficiency has been balanced in evolution by an advantage
in survival—an increased resistance to falciparum malaria shown by female carriers of the
mutation. Note: Sickle cell trait and β-thalassemia minor also confer resistance.

 Diminished G6PD activity impairs the ability of the cell to form the NADPH that is
essential for the maintenance of the reduced glutathione pool. This results in a decrease in
the cellular detoxification of free radicals and peroxides formed within the cell.
 Glucose-6-Phosphate Dehydrogenase Deficiency
 Additional oxidation of membrane proteins causes the red cells to be rigid (less deformable),
and they are removed from the circulation by macrophages in the spleen and liver.
 Although G6PD deficiency occurs in all cells of the affected individual, it is most severe in
erythrocytes, where the pentose phosphate pathway provides the only means of generating
NADPH. Other tissues have alternative sources for NADPH production (such as NADP+ -
dependent malate dehydrogenases,) that can keep glutathione reduced.
 The erythrocyte has no nucleus or ribosomes and cannot renew its supply of the enzyme.
 Thus, red blood cells are particularly vulnerable to enzyme variants with diminished stability.
 However, some patients with G6PD deficiency develop hemolytic anemia if they are treated
with an oxidant drug, ingest fava beans, or contract a severe infection.

 1. Oxidant drugs: Commonly used drugs that produce hemolytic anemia in patients with G6PD
deficiency are best remembered from the mnemonic AAA—Antibiotics (for example,
sulfamethoxazole and chloramphenicol), Antimalarials (for example, primaquine but not
quinine), and Antipyretics (for example, acetanilid but not acetaminophen).
 2. Favism: Some forms of G6PD deficiency, for example the Mediterranean variant, are
particularly susceptible to the hemolytic effect of the fava (broad) bean, a dietary staple in the
Mediterranean region. Favism, the hemolytic effect of ingesting fava beans, is not observed in
all individuals with G6PD deficiency, but all patients with favism have G6PD deficiency.
 3. Infection: Infection is the most common precipitating factor of hemolysis in G6PD
deficiency. The inflammatory response to infection results in the generation of free radicals in
macrophages, which can diffuse into the red blood cells and cause oxidative damage.
Pathways of glucose 6-phosphate
metabolism in the erythrocyte.