1. Pentose Phosphate Shunt
Hexose Monophosphate Shunt
(HMP Shunt)

2. HMP Shunt
• HMP is a minor oxidation pathway for glucose
• It is an alternative pathway which involves
phospho–pentoses as intermediates for
purposes other than energy production

3. HMP Shunt
• HMP occurs in the Cytoplasm of:
1. Liver
2. Lactating mammary gland
3. Adipose tissue
4. Red blood cells
5. Adrenal cortex

4. Rate
limiting
Oxidation enzyme
Oxidative Decarboxylation

5. Hexose Monophosphate Shunt
• The first step:

6. Hexose Monophosphate Shunt
• Reactions of the hexose monophosphate
pathways:
• Enzymes numbered above are
1. Glucose 6-phosphate dehydroganase
and gluconolactone hydrolyase
2. 6-phosphogluconate dehydrogenase
3. Phosphopentose isomerase
4. Phosphopentose epimerase
5. Transketolase (TPP cofactor)
6. Transaldolase
7. Transketolase (TPP cofactor)

7. 3 molecules
3rd 2nd TPP 1st
TPP
TPP

8. 2 molecules
1 molecule

9. Regulation of HMP Shunt
1. Insulin increases the activity of HMP pathway
by stimulating the synthesis of
dehydrogenases involved in HMP pathway
2. Galactose-1-phosphate inhibits G-6-P DH

10. Metabolic Significance of HMP Shunt
1) It is the only source of phosphorylated
pentoses which used for the synthesis of:
A. Nucleotides: ATP & GTP
B. Coenzymes: FMN, FAD, NAD+
C. Certain vitamins: B2 & B12
D. Nucleic acids: DNA & RNA

11. Metabolic Significance of HMP Shunt
2) It is the major source of NADPH+ which is essential for:
A. Fatty acid synthesis for lipogenesis which occurs in
liver, adipose tissue & lactating mammary gland
B. Steroid synthesis (Adrenal cortical hormones, Sex
hormones) which is active in adrenal cortex, testes,
ovaries & placenta
C. Act as coenzyme of glutathione reductase which keeps
GSH in reduced state

12. Other NADPH+ Source
• Malic enzyme (In the cytoplasm) catalyze the oxidative
decarboxylation of malate to pyruvate and CO2, with the
concomitant reduction of the cofactor NADP+ to NADPH
Malic enz.
• Malate + NADP+ pyruvate + CO2 + NADPH

13. Metabolic Significance of HMP Shunt
3) NADPH is essential for keeping the reduced form of
glutathione (G-SH), which is essential for keeping the red
blood cell wall intact, since G-SH is essential for:
A. Keeping iron of Hb in Ferrous state (Fe2+)
B. Keeping globin of Hb in native structure
C. Preventing accumulation of free radicals & H2O2 in RBCs
So Keeping RBCs wall intact preventing hemolysis

14. Glutathione Protects us from Oxidation
1 2 3
4 Protects RBC's against hemolysis

15. Oxidized Glutathione Reduced Glutathione

16. Rate limiting enzyme

17. Favism or Primaquine Sensitivity
Fava beans)
Aspirin)
Metabolite (Like, Oxidation H2O2
Sulfa Drugs)
Primaquine)
H2O2 + 2 G-SH Glutathione Peroxidase 2 H2O + G-S-S-G
G-S-S-G + NADPH Glutathione Reductase 2 G-SH + NADP+
Glucose-6-phosphate + NADP+ Glucose-6-P DH
NADPH + 6-phospho
gluconolactone

19. Fava Beans

20. Child with
Favism
With signs of
anemia
(decreased red
blood cell count,
jaundice, etc.)

21. Conclusion
– Favism is a significant disease in society today
– it plays a role similar to sickle cell anemia
– It may act as a defense mechanism against malaria
– The unusually high number of oxidants in the blood can
kill the malaria, bacteria, Plasmodium falciparum
– Interestingly, the highest incidence of this disease is
found in areas where malaria is present (Mediterranean
and African areas)

22. Glucuronic Acid Synthesis

24. HMP Shunt

26. Metabolic Significance of
Glucuronic Acid
• Glucuronic acid is used in:
1. Synthesis of Proteoglycans
(Glycosaminoglycans, GAGs)
2. Excretion of Bilirubin and Steroid compounds
(Glucuronidation)
3. Detoxification of certain drugs and their
metabolites by increasing their solubility
(Glucuronidation)

27. Official Names of Malic Enzymes
• Malate dehydrogenase (decarboxylating)
• Malic enzyme
• NADP-Malic enzyme
• Pyruvic-Malic carboxylase
• Malate + NADP+ Malic enz pyruvate +
CO2 + NADPH