The pentose phosphate pathway following the curriculum of medical biochemistry of MBBS course

1. The pentose
phosphate pathway
DR. FARHANA ATIA
ASSOCIATE PROFESSOR
DEPARTMENT OF BIOCHEMISTRY
NILPHAMARI MEDICAL COLLEGE, NILPHAMARI

2. The pentose phosphate pathway
It is an alternative route for the metabolism of
glucose
It does not lead to formation of ATP
Other name of PPP: Hexose monophosphate
shunt pathway (HMPS)

3. Biomedical Importance
There is no ATP directly consumed or produced in this
pathway but it has two major functions
1. Formation of NADPH for synthesis of fatty acids &
steroids, and maintaining reduced glutathione for
antioxidant activity
2. Provide ribose for nucleotide & nucleic acid synthesis
 Genetic deficiency of glucose-6-phosphate
dehydrogenase, the first enzyme of the PPP, causes
hemolytic anemia

4. Importance of NADPH
Reductive synthesis of FA, steroid, cholesterol
Detoxification & drug metabolism in the liver in
cytochrome P-450 monooxygenase system
Support antioxidant activity in RBC & prevent
hemolysis of RBC
Production of superoxide & free radical in
phagocytes to kill bacteria.

5. HMPS NADPH+H G-S-S-G
Oxidized
glutathione
2H₂O
2H
NADP 2GH H₂O₂
Glutathione
reductase
Glutathione
peroxidase
Antioxidant activity in RBC

6. In RBC, the PPP is the sole source of NADPH for the
reduction of oxidized glutathione catalyzed by
glutathione reductase
Reduced glutathione removes H₂O₂ in a reaction
catalyzed by glutathione peroxidase
 Accumulation of H₂O₂ may decrease the lifespan of
erythrocyte by causing oxidative damage to the cell
membrane, leading to hemolysis
Deficiency of glutathione reductase leads to
hemolytic anemia

7. Salient features:
Substrate: Glucose-6-Phosphate
Product: Ribose, 2NADPH, CO₂
Site: Liver, lactating mammary gland, adrenal cortex,
adipose tissue, gonads, RBC, thyroid. Occurs virtually all
tissue.
Compartment: Cytoplasm
Nature: Catabolic
The pentose phosphate pathway

8. Steps of PPP
2 phases
1. Irreversible oxidative phase
2. Reversible non-oxidative phase
Irreversible oxidative phase
Dehydrogenation & decarboxylation
G-6-P  Ribulose-5-P
Generates NADPH, CO₂

9. Steps of PPP
Reversible non-oxidative phase
Ribulose-5-P  G-6-P
Generates ribose precursors
Two enzymes involved
Transketolase
Tansaldolase
Full pathway- 3 interconnected cycles, substrate &
end product is Glucose-6-phosphate

10. Flowchart
of PPP

11. Uronic acid pathway

12. Uronic acid pathway
Alternate oxidative pathway for glucose metabolism
It does not lead to formation of ATP
In liver, it catalyzes the conversion of glucose to
glucuronic acid, ascorbic acid (except human) &
pentoses

13. Uronic acid pathway
Glucuronic acid is significant for the conjugation &
excretion of metabolites & foreign chemicals as
glucuronides
A deficiency in the pathway leads to essential
pentosuria

14. Glucuronate
Glucuronate is formed from glucose for
Its incorporation into proteoglycans
Glucuronide conjugation with substrates such as
steroid hormone, bilirubin, drugs that are excreted in
urine or bile