HMP Shunt | Hexose Monophosphate Pathway | Pentose Phosphate Pathway | Phosphogluconate Pathway

This PPT contains HMP Shunt, Reactions of the pathway i.e. Oxidative & Non-oxidative. Glucose-6-Phosphate dehydrogenase (G6PD) deficiency, Regulation of Pathway, Significance of HMP shunt

2. HMP SHUNT
HMP shunt is also called as:
Hexosemonophosphatepathway.
Pentose phosphate pathway.Pentose phosphate pathway.
Phosphogluconatepathway.
Alternative pathway to glycolysisand TCA
cycle for the oxidation of glucose.

3. •The pentose phosphate pathway is an alternative
route for the metabolism of glucose. It does not
generate ATP but has two major functions:
The formation of NADPH for synthesis of fatty The formation of NADPH for synthesis of fatty
acids and steroids.
The synthesis of ribose for nucleotide and nucleic
acid formation.

4. Reactions of the pathway
•The reactions of HMP shunt is divided into
two phases—
Oxidative. Oxidative.
Non-oxidative.

5. Oxidative phase
•Glucose 6-phosphate is converted to
6-phosphogluconolactoneby
“Glucose 6-phosphate
dehydrogenase(G6PD)”
whichis an NADP-dependent
enzyme .
•6-phosphogluconolactoneis then hydrolysedto •6-phosphogluconolactoneis then hydrolysedto
6-phosphogluconateby the
“gluconolactonehydrolase”.
•The next reaction involving the synthesis of NADPH is
catalysedby
“6-phosphogluconate dehydrogenase”
to
produce 3 keto6-phosphogluconate which then
undergoes decarboxylationto give Ribulose5-
phosphate.

7. Non-oxidative phase
•Ribulose5-phosphate is converted to Xylulose
5-phosphateby
“Ribulose5-Phosphate
epimerase”.•Ribulose5-phosphate is converted to Ribose
5-phosphateby “
Ribose 5-phosphate
ketoisomerase
”

8. •2 carbon moiety from xylulose5-phosphate is transferred to
ribose 5-phosphate by
“transketolase”
which give rise to 3-
carbon glyceraldehyde3-phosphate and a 7-carbon
sedoheptulose7-phosphate.
•Transketolaseis dependent on the coenzyme thiamine
pyrophosphate (TPP) and Mg2+ ions.
•3-carbon fragment from Sedoheptulose7-phosphate is •3-carbon fragment from Sedoheptulose7-phosphate is
transferred to Glyceraldehyde3-phosphate by
“transaldolase”
which give rise to fructose 6-phosphateand 4 carbon
erythrose4-phosphate.
•2-carbonfragment fromxylulose5-phosphateis transferred to
erythrose4-phosphateby enzyme
“transketolase”
to generate
fructose 6-phosphate and glyceraldehyde3-phosphate.

10. •Fructose 6-phosphate and glyceraldehyde3-
phosphate can be further catabolizedthrough
glycolysisand citric acid cycle.
•Glucose may also be synthesized from these
two compounds.

11. Red indicates:No. of molecule
Blue indicates: No. of carbon
HMP shunt Overview

12. Glucose-6-Phosphate dehydrogenase
(G6PD) deficiency
•G6PD deficiency is an inherited sex-linked trait.
The gene of G6PD is on the X chromosomes,
hence males are affected.
•Although the deficiency occurs in all the cells of
the affected individuals, it is more severe in RBC.
•Although the deficiency occurs in all the cells of
the affected individuals, it is more severe in RBC.
•HMP shunt is the only means of providing NADPH
in the erythrocytes. Decreased activity of G6PD
impairs the synthesis of NADPH in RBC. This
results in the accumulation of methemoglobinand
peroxides in erythrocytes leading to hemolysis.

13. •Clinical manifestations in G6PD deficiency : Most
of the patients with G6PD deficiency do not
usually exhibit clinical symptoms. Some of them,
however, develop hemolytic anemia if they are
administered oxidant drugs or exposed to a
severe infection. severe infection.
•Severe infection results in the generation of free
radicals (in macrophages) which can enter RBC
and cause hemolysis(due to decreased NADPH
and reduced GSH)

14. •G6PD deficiency and resistance to malaria : It is
interesting to note that G6PD deficiency is
associated with resistance to malaria (caused by
Plasmodium falciparum).
•The parasites that cause malaria are dependent
on HMP shunt and reduced glutathione for their on HMP shunt and reduced glutathione for their
optimum growth in RBC. Therefore, G6PD
deficiency—which is seen frequently in Africans—
protects them from malaria, a common disease in
this region.

15. •Biochemical diagnosis can be done by detecting
reduced activity of G6PD in RBC. The management of
G6PD deficiency includes avoiding oxidative stress and
symptomatic treatment of hemolysis.
•Wernicke-Korsakoffsyndrome: An alteration in
transketolaseactivity that reduces its affinity with
thiamine pyrophosphate is the biochemical lesion. thiamine pyrophosphate is the biochemical lesion.
•The symptoms of Wernicke-Korsakoffsyndrome
include mental disorder, loss of memory and partial
paralysis. The symptoms are manifested in vitamin-
deficient alcoholics.

16. Regulation of Pathway
•Rate limiting step of this pathway is catalysed
by Glucose 6 Phosphate dehydrogenase
enzyme.
•This enzyme is inhibited by NADPH.
•Main regulation of this pathway is at the level
of NADP+.

17. Significance of HMP shunt
•HMP shunt generates two important products—
Pentoses
NADPHNADPH
Which are needed for the biosynthetic reactions
and other functions.

18. References:
•Biochemistry 5
th
Edition by Dr. U. Satyanarayana& Dr. U. Chakrapani
•Harper’s Illustrated Biochemistry, twenty-sixth edition by Robert K. Murray, Daryl K. Granner, Peter A. Mayes &
Victor W. Rodwell
•Lehninger, Principle of Biochemistry, Fourth edition by David L. Nelson and Michael M. Cox