Hexose monophosphate pathway (HMP)

1. Hexose monophosphate pathway
(HMP)
 Dr. Aswartha Harinath Reddy
 Department of Life Sciences
 Srikrishnadevaraya University
 Anantapur –A.P. India

2.  HMP shunt pathway also known as pentose phosphate
pathway or phosphogluconate pathway or Warburg–Dicken-
Lipman pathway is a metabolic pathway parallel or
alternative to glycolysis.
 In Hexose monophosphate pathway in which oxidation of
glucose 6-phosphate takes place to produce pentoses.
 It generates NADPH and pentoses (5-carbon sugars) as well as
ribose 5-phosphate, a precursor for the synthesis of
nucleotides.

3.  It involve oxidation of glucose, About 10% of
glucose entering in this pathway/day.
 The liver & RBC metabolise about 30% of glucose
by this pathway.

4. Location of the pathway:
 The pathway located in the cytosol of the cells.
 The tissues such as liver, adipose tissue, adrenal gland, erythrocytes
are highly active in HMP.
 Most of these tissues are involved in biosynthesis of fatty acids and
steroids which are dependent on the supply of NADPH.
 This NADPH is supplied by HMP.

5.  The HMP pathway starts with glucose 6-phosphate.
 No ATP is directly utilized or produced in HMP shunt.
 There are two distinct phases in the pathway.
 The first is the oxidative phase, in which NADPH is generated,
and the second is the conversion of Pentoses into Hexoses (Non
oxidative phase).

6. Oxidative phase:
Step1: Oxidation of Glucose 6 phosphate to 6-phosphogluconolactone:
 This phase starts with the oxidation of 6 molecules glucose 6-
phosphate by the enzyme glucose 6-phosphate dehydrogenase to
yield 6-phosphogluconolactone.
 This enzyme is an NADP dependent enzyme, where NADP+
reduced to NADPH + H+.

7. Step 2: Hydrolysis
 The 6-phosphogluconolactone is unstable it hydrolysis to 6-
phosphogluconic acid.
 The enzyme catalyze the reaction is gluconolactonase.

8. Step 3: Oxidation and decarboxylation:
 The 6-Phosphogluconic acid is oxidatively decarboxylated by
the enzyme 6-Phosphogluconic acid dehydrogenase.
 The 6 molecules of NADP are reduced to NADPH, 6
molecules of CO2 are released and 6 molecules, of Ribulose-
5-Phosphate are produced.

9. Non oxidative phase:
Step 4: Isomerization and Epimerization of Ribulose 5-phosphate:
 The 6 molecules of Ribulose-5-P isomerise into 4 molecules of Xyluose-5-
Phosphate and 2 molecules of Ribose-5-Phosphate in the presence of Ribulose
phosphate-5-epimerase and Pentose phosphate isomerase respectively.
Epimer
Isomer
5

10. Step 5:
 2 mols. of xylulose-5-Phosphate and 2 mols. of Ribose-5-
phosphate combine in the presence of Transketolase to form 2
mols. of Sedoheptulose-7-Phosphate and 2 mols. of 3-
Phosphoglyceraldehyde.

11. Step 6:
 2 mols. of Sedoheptulose-7-Phosphate and 2 mols. of 3-
Phosphoglyceraldehyde combine in the presence of
Transaldolase to form 2 mols. of Fructose-6-Phosphate and 2
mols. of Erythrose-4-Phosphate (4-carbon atoms sugar).

12. Step 7:
 2 mols. of Erythose-4-Phosphate react with remaining two mols. of
xylulose-5-Phosphate (see reaction No. 4 and 5) in the presence of
Transketolase to form 2 mols. of Fructose- 6-Phosphate and 2
mols of 3-Phosphoglyceraldehyde.
3
2

13. Step:8
 One mol. of 3-phosphoglyceraldehyde isomerises into
dihydroxyacetone phosphate. In the presence of enzyme
Phosphotriose isomerase.

14. Step 9:
 Remaining one mole, of 3-Phosphoglyceraldehyde unites
with Dihydroxyacetone phosphate in presence of Aldolase to
form one mol. of Fructose 1, 6-bisphosphate.
 The latter, in the presence of Phosphatase one mol. of
Fructose 1, 6-bisphosphate forms one mol. of Fructose 6-
Phosphate.

15. Step 9

16. Step 10: Isomerisation:
 5 molecules of Fructose-6-phosphate produced in
reactions 6, 7 and 9, isomerise into 5 mols. of Glucose-6-P
in presence of Phosphohexose isomerase.

18. Significance of HMP Shunt:
Producing NADPH :
 Hexose Mono-Phosphate Shunt producing Biochemical
reductant NADPH. This reductant participating in Fatty acid
Biosynthesis.
 NADPH is co-factor for Glutathione Reductase.
 This enzyme neutralizes the superoxide and hydroxyl radicals
from hydroxyl peroxide molecules.

19. Producing Ribose-5-Phosphate:
 Hexose MonoPhosphate shunt provides Ribose-5-Phosphate for
the Purine biosynthesis.
Producing Glycolytic Intermediate:
 In the Hexose MonoPhosphate Shunt Pathway, few molecules of
Glycolytic intermediates are produced these are directly involves
in Glycolysis.
 The molecules are Glyceraldehyde-3-Phosphate and Fructose-6-
Phosphate.