PENTOSE

PHOSPHATE
PATHWAY
PERESENTED BY ELLY 5TH YEAR MEDICAL
STUDENT UNU
DEPARTMENT OF BIOCHEMISTRY
 Definition
• The pentose phosphate pathway(PPP): is an alternative
route for the oxidation of glucose.
• Formation of Fructose-6-phosphate and glyceraldehyde-
3- phosphate from glucose-6-phosphate.
• It is the pathway for formation of pentose phosphate.
• It is also called hexose monophosphate shunt
Location
• cytosol.
Site
• The pathway is found in all cells.
• Characteristics of Pentose Phosphate Pathway
• It is a multicyclic process in which three molecules
of glucose-6-phosphate give rise to three molecules
of CO2 and three molecules of 5-carbon sugars,
(ribulose-5-phosphate).
• The three molecules of ribulose-5-phosphate are
arranged to generate two molecules of fructose-6-
phosphate and one molecule of glyceraldehyde-3-
phosphate.
• It does not generate ATP.
Reactions of the Pentose Phosphate
Pathway
• The reactions of the pathway are divided
into two phases:
1. Phase I : Oxidative irreversible phase
2. Phase II : Non-oxidative reversible phase.
 Reactions of phase I (oxidative irreversible phase)

• In the first phase, glucose-6-phosphate

undergoes dehydrogenation and
decarboxylation to give pentose, ribulose-5-
phosphate with generation of NADPH
Step 1. Dehydrogenation of glucose-6-
phosphate to 6-phosphogluconolactone,
catalyzed by glucose-6-phosphate
dehydrogenase which is an NADP
dependent enzyme
Step 2. 6-phosphogluconolactone is hydrolyzed by
6- phosphogluconolactone hydrolase to 6-
phosphogluconate.
Step 3. The subsequent oxidative decarboxylation
of 6-phosphogluconate is catalyzed by 6-
phosphogluconate dehydrogenase, which also
requires NADP as hydrogen acceptor.
This irreversible reaction produces ribulose-5-
phosphate, CO2 and second molecule of NADPH.
 Reactions of phase II(nonoxidative, reversible phase)

• In the second phase, ribulose-5-phosphate is

converted to fructose-6-phosphate by a series of
reactions.
Step 4. Ribulose-5-phosphate formed in the phase I
now serves as substrate for two differerent
enzymes:
i. Ribulose-5-phosphate epimerase catalyzes the
epimerization of ribulose-5-phosphate to xylulose-5-
phosphate.
ii. Ribulose-5-phosphate isomerase catalyzes
Step 5. Transketolase catalyzes the transfer
of two carbon units from xylulose-5-phosphate
to ribose-5-phosphate, producing a 7-carbon,
sedoheptulose-7-phosphate and
glyceraldehyde- 3-phosphate.
• The reaction requires coenzyme thiamine
pyrophosphate (TPP) and Mg2+ ions.
Step 6. Transaldolase catalyzes the transfer
of a three carbon dihydroxyacetone group from
sedoheptulose- 7-phosphate to glyceraldehyde-
3-phosphate to form fructose-6-phosphate and
Step 7. Further reaction again involves
transketolase, which catalyzes the transfer of
the two carbon units from xylulose-5-phosphate
to erythrose-4- phosphate producing fructose-6-
phosphate and glyceraldehyde-3-phosphate.
Step 8. Fructose-6-phosphate and
glyceraldehyde-3- phosphate can be further
catabolized through glycolysis and citric acid
cycle.
Glycolysis Pentose phosphate pathway
Oxidation occurs utilizing NAD+ Oxidation occurs utilizing NADP
as an H-acceptor as an H-acceptor
Aerobic as well as anaerobic Anaerobic process
process
CO2 is not produced at all CO2 is a characteristic product
ATP is generated, where it is a ATP is not generated
major function
Ribose phosphates are not Ribose phosphates are
generated generated
80-90% of glucose oxidized by 10-20% glucose oxidized by
glycolysis pentose phosphate pathway
• Regulation of Pentose Phosphate Pathway
• The first step in the pathway, catalyzed by glucose- 6-
phosphate dehydrogenase (G-6-PD) is the rate limiting step.
• The activity of this enzyme is regulated by cellular
concentration of NADPH. NADPH is a competitive inhibitor of
the enzyme G-6-PD.
• An increased concentration of NADPH decreases the activity of
G-6-PD, for example: – Under well-fed condition, the level of
NADPH decreases and pentose phosphate pathway is stimulated.
– However, in starvation and diabetes, the level of NADPH is high
and inhibits the pathway.
• Insulin is also involved in the regulation of pentose phosphate
pathway. It enhances the pathway by inducing the enzyme G-6-
PD and 6-phosphogluconolactone dehydrogenase
• Disorders of Pentose Phosphate Pathway
Deficiency of Glucose-6-phosphate
dehydrogenase (G-6-PD)
• Glucose 6-phosphate dehydrogenase deficiency is
Xlinked inherited disorder, characterized by
hemolytic anemia, due to excessive hemolysis.
• This enzyme catalyzes the first step in the pentose
phosphate pathway and is needed for the formation of
NADPH.
• The NADPH is required for the detoxification of
H2O2 in red blood cell .
In deficiency of G-6- PD, the production of
NADPH is inadequate both to restore the
reduced glutathione level and to maintain
the RBC cell membrane. The consequence is
destruction of the red blood cells and severe
hemolytic anemia.
• Most of the patients of G-6-PD deficiency
are asymptomatic and do not show hemolytic
anemia under normal condition. However,
they develop severe hemolytic anemia when
they are exposed to certain antibiotic,
antimalarial (primaquine) or antipyretic
 Wernicke-Korsakoff syndrome
• This is a genetic disorder due to reduced activity of the
TPP-dependent transketolase enzyme. The reduced
activity of transketolase is due to reduced affinity for
TPP, whereas the other TPP dependent enzymes are
normal. Therefore, in the chronic thiamine deficiency
the transketolase enzyme has a much reduced activity
leading to the Wernicke- Korsakoff syndrome.
• The symptoms of Wernicke-Korsakoff syndrome
include weakness, mental disorder, loss of memory,
partial paralysis, etc.
 G-6-PD deficiency and resistance to malaria
• The malarial parasite, Plasmodium falciparum
infects the red blood cell, where it depends on the
reduced glutathione and the products of the
pentose phosphate pathway for its optimum growth.
• Therefore, persons with G-6-PD deficiency cannot
support growth of this parasite and thus are less
prone to malaria than the normal person.
 Significance of Pentose Phosphate Pathway
• The pentoses (ribose-5-phosphate) required for
the biosynthesis of nucteotide and nucleic acids
(RNA and DNA) are provided by pentose phosphate
pathway.
• It provides a route for the interconversion of
pentoses and hexoses.
• It generates NADPH which plays important role
in several other biological processesas given below.
– NADPH is required for the biosynthesis of fatty acids,
cholesterol, steroid hormones and neurotransmitters.
– It is required for oxidation-reduction reactions involved in
detoxification, e.g.for detoxification of drugs by microsomal
cytochrome P450 mono-oxygenase and for reduction of
oxidized glutathione.
– In RBC, NADPH is required to maintain the level of reduced
glutathione. The reduced glutathione protects the RBC
membrane from toxic effect of H2O2 by reducing H2O2 to
H2ONADPH also keeps iron of hemoglobin in reduced ferrous
(Fe2+) state and prevents the formation of methemoglobin.
– NADPH is necessary for phagocytosis carried out by white blood
cell.
 Trial
Qn1. Muscle glycogen is not available for maintenance
of blood glucose concentration because:
a. Muscle lacks glucose-6-phosphatase activity
b. There is insufficient glycogen in muscle
c. Muscle lacks glucose transporter GLUT-4
d. Muscle lacks glucagon receptors
Qn2. Both glycolysis and gluconeogenesis involve which of
the following enzymes:
a. Pyruvate carboxylase
b. Hexokinase
c. Aldolase
d. Phosphofructokinase
Qn3. The principal source of glucose after an overnight fast
is:
a. Gluconeogenesis
b. b. Glycolysis
• c. Glycogenolysis
• d. HMP pathway
Qn4. Von Gierke’s disease is characterized by deficiency of the enzyme:
a. Glucokinase
b. Glucose-6-phosphatase
c. Phosphoglucomutase
d. Glycogen synthase
Qn5. McArdle syndrome involves a deficiency of which of the following enzymes:
a. Hepatic phosphorylase
b. Muscle phosphorylase
c. Debranching enzyme
d. Hepatic glycogen synthase
Qn6. Gluconeogenesis can proceed from all of the following, except:
a. Pyruvate
b. Palmitic acid
c. Propionyl-CoA
d. Oxaloacetate
Qn7 Gluconeogenesis, must bypass irreversible reactions
of glycolysis, except:
a. Hexokinase
b. Phosphohexose isomerase
c. Pyruvate kinase
d. Phosphofructokinase
Qn8 Rapoport leubering cycle in RBC produces:
a. ATP
b. NADPH
c. 2,3-bisphosphoglycerate
d. 1,3-bisphosphoglycerate
Qn9. The net production of ATP when glycolysis occurs via
Rapoport Lubering route:
a. Two
b. Six
c. Eight
d. Zero
Qn10.In erythrocytes, the end product of glycolysis is:
a. Pyruvate
b. Acetyl-CoA
c. Lactate
d. 2,3 Bisphosphoglycerate
Qn11. In erythrocytes, the end product of glycolysis is:
a. Pyruvate
b. Acetyl-CoA
c. Lactate
d. 2,3 Bisphosphoglycerate
Qn12. Gluconeogenesis occurs in which of the following:
a. Heart
b. Erythrocytes
c. Liver
d. Lungs
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