The document summarizes the hexose monophosphate pathway (HMP pathway), also known as the pentose phosphate pathway. It has two phases - an oxidative phase that generates NADPH, and a non-oxidative phase that converts pentoses to hexoses. The pathway takes place in the cytosol and is important in the liver, red blood cells, and other tissues for generating NADPH for biosynthesis of fatty acids and steroids. It involves the oxidation of glucose-6-phosphate through a series of steps to ultimately regenerate glucose-6-phosphate while producing NADPH and pentose sugars.

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.