The hexose monophosphate (HMP) shunt is an alternative pathway to glycolysis for oxidizing glucose. Unlike glycolysis, it has selective tissue distribution and produces reducing equivalents like NADPH and pentose phosphates that are used for anabolic reactions rather than ATP. NADPH produced is used for biosynthesis of fatty acids, cholesterol, and other compounds. Ribose-5-phosphate produced is used for nucleotide and nucleic acid synthesis. The HMP shunt provides reducing power and pentose phosphates essential for biosynthesis in various tissues.

1. Hexose Monophosphate (HMP)
Shunt
R. C. Gupta
M.D. (Biochemistry)
Jaipur, India

2. The main pathway for oxidation of
glucose is glycolysis
Hexose monophosphate shunt is an
alternate pathway for oxidation of glucose
Unlike glycolysis, HMP shunt has a
selective tissue distribution

3. The proportion of glucose oxidized via
HMP shunt differs in different tissues
The proportion depends upon the need
for NADPH and ribose
The requirements keep on changing

4. HMP shunt is said to be an oxidative
pathway but its role is anabolic
NADPH and ribose produced in HMP
shunt are used in anabolic reactions
HMP shunt doesn’t produce any ATP

5. HMP shunt is also known as:
Pentose phosphate pathway
Phosphogluconate oxidative
pathway
Direct oxidative pathway

6. Intracellular location of HMP shunt is
cytosol
Oxidation of glucose occurs in the
absence of oxygen in HMP shunt
The reducing equivalents are taken up
by NADP

7. Unlike NADH, NADPH cannot be
oxidized in the respiratory chain
NADPH is used mainly for reductive
synthesis e.g. synthesis of fatty acids
It has a number of other functions as well

8. Hexose monophosphate is oxidized as well
as decarboxylated in HMP shunt
Decarboxylation produces a pentose
phosphate
The pentose phosphate is ribulose-5-
phosphate
Ribulose-5-phosphate can be isomerized
to ribose-5-phosphate

9. Ribose-5-phosphate can be used to form
ribonucleotides
Ribonucleotides can be converted into
deoxyribonucleotides
Thus, HMP shunt provides ribo- and
deoxyribo-nucleotides for the synthesis of
nucleic acids

10. After meeting the need for nucleotides,
some ribulose-5-phosphate may remain
unutilized
The unutilized ribulose-5-phosphate is
reconverted into glucose-6-phosphate

11. Oxidation of one molecule of glucose-6-
phosphate in HMP shunt produces:
One molecule of CO2
Two molecules of NADPH
One molecule of pentose phosphate

12. Oxidation of six molecules of glucose-6-
phosphate in HMP shunt produces:
Six molecule of CO2
Twelve molecules of NADPH
Six molecule of pentose phosphate
Six pentose phosphate molecules can
form five glucose-6-phosphate molecules

13. HMP shunt is present in:
• Liver
• Adipose tissue
• Lactating mammary glands
• Adrenal cortex
• Testes
• Thyroid gland
• Erythrocytes

14. The reactions of HMP shunt pathway may
be divided into three phases:
Oxidation of hexose monophosphate
Decarboxylation of hexose monophosphate
Regeneration of hexose monophosphate
The second and third phase together are
also called the non-oxidative phase

15. In the first phase, two pairs of reducing
equivalents are removed from glucose-6-
phosphate
Glucose-6-phosphate is first reduced to
6-phosphogluconolactone by glucose-6-
phosphate dehydrogenase (G-6-PD)
The reducing equivalents are accepted
by NADP

16. G-6-PD is inhibited by:
Fava beans and
Sulphonamides and quinacrine
This can limit the availability of NADPH

17. A molecule of water is added to 6-phospho-
gluconolactone by gluconolactone hydrolase
The product is 6-phosphogluconate, a
straight chain phosphorylated compound
A pair of reducing equivalents is trans-
ferred from 6-phosphogluconate to NADP
The product is 3-keto-6-phosphogluconate

19. 3-Keto-6-phosphogluconate is
then decarboxylated
The reaction is catalysed by 6-
phosphogluconate dehydrogenase
The product is a pentose sugar,
ribulose-5-phosphate

20. Some of the ribulose-5-phosphate
molecules are isomerized to ribose-5-
phosphate
The reaction is catalysed by ribose-5-
phosphate ketoisomerase
Some ribulose-5-phosphate molecules
are epimerized by ribulose-5-phosphate
epimerase to xylulose-5-phosphate

22. The final phase begins now
The purpose of this phase is to
reconvert unutilized ribulose-5-
phosphate into glucose-6-phosphate

23. For reconversion, one molecule of ribose-5-
phosphate and two molecules of xylulose-5-
phosphate react with each other
By the end, two molecules of fructose-6-
phosphate and one molecule of
glyceraldehyde-3-phosphate are formed

24. To begin with, xylulose-5-phosphate
reacts with ribose-5-phosphate
A glycol aldehyde moiety is transferred
from the former to the latter
The former is converted into
glyceraldehyde-3-phosphate and the
latter into sedoheptulose-7-phosphate

26. A dihydroxyacetone moiety is then
transferred from sedoheptulose-7-phos-
phate to glyceraldehyde-3-phosphate
The former is converted into erythrose-4-
phosphate and the latter into fructose-6-
phosphate

28. Erythrose-4-phosphate now receives a
glycol aldehyde moiety from another
molecule of xylulose-5-phosphate
The former is converted into fructose-6-
phosphate and the latter into
glyceraldehyde-3-phosphate

30. Thus, three molecules of glucose-6-
phosphate are first converted into three
molecules of pentose-5-phosphate
These three are converted into two mole-
cules of fructose-6-phosphate and one
molecule of glyceraldehyde-3-phosphate

31. Fructose-6-phosphate molecules are isomer-
ised to two glucose-6-phosphate molecules
Thus, out of three molecules of glucose-6-
phosphate that entered the pathway:
Two molecules of glucose-6-phosphate
are regenerated
The third is converted into glyceralde-
hyde-3-phosphate

33. Three other molecules of glucose-6-
phosphate undergo the same sequence
of reactions
Two molecules of glucose-6-phosphate
are regenerated; the third is converted
into glyceraldehyde-3-phosphate

34. Thus, when six molecules of glucose-6-
phosphate are oxidized in the HMP shunt:
Four molecules of glucose-6-phosphate
are regenerated
Two molecules of glyceraldehyde-3-
phosphate are formed

35. Out of two glyceraldehyde-3-phosphate
molecules, one is converted into
dihydroxyacetone phosphate (DHAP)
One glyceraldehyde-3-phosphate molecule
and one DHAP molecule can form one
glucose-6-phosphate molecule
Thus, fifth glucose-6-phosphate molecule
is regenerated

37. The overall reaction leading to the
oxidation of six molecules of glucose-6-
phosphate may be summed up as:
6 Glucose-6- +12 NADP+ + 7 H2O →
5 Glucose-6- + Pi + 6 CO2 + 12 NADPH + 12 H+

38. Glucose-6-phosphate dehydrogenase is
the regulatory enzyme of HMP shunt
It is regulated by induction and allosteric
mechanism
Its synthesis is induced by insulin
NADP is its allosteric activator
Regulation

39. Importance of HMP shunt
Provision NADPH
Production of
ribose-5-phosphate
Restoring the level of reduced
glutathione in erythrocytes

40. An important function of HMP shunt is to
provide NADPH
Complete oxidation of one molecule of
glucose in HMP shunt produces twelve
molecules of NADPH
NADPH

41. NADPH is used mainly for the synthesis of:
Fatty acids
Cholesterol
Steroid hormones
Some amino acids
Nucleotides
HMP shunt is highly active in tissues synthe-
sizing these compounds

42. Ribose-5-phosphate is an intermediate of
HMP shunt
It is used for synthesizing nucleotides and
nucleic acids
Ribose-5-phosphate

43. In erythrocytes, glutathione is oxidized to
detoxify hydrogen peroxide and free radicals
NADPH is required for restoring reduced
glutathione
This prevents premature destruction of
erythrocytes
Reduced glutathione

45. In hereditary glucose-6-phosphate dehydro-
genase deficiency, haemolysis occurs due to
decreased production of NADPH
Drugs like quinacrine and primaquin, which
increase oxidative stress, can precipitate
haemolysis

46. Two intermediates are common to HMP
shunt and glycolysis
These are glyceraldehyde-3-phosphate and
fructose-6-phosphate
HMP shunt and glycolysis can interconnect
through these two
Due to this interconnection, dietary pentoses
can enter glycolysis via HMP shunt