Metabolism of carbohydrate in the one of the pathway "Hexose Monophosphate Shunt".

2. ▪ Hexose Monophosphate Shunt is an
alternative pathway of glucose
oxidation for the production of NADPH
and pentose sugars.
▪ It is not involved in the generation of
energy.
Hexose Monophosphate Shunt

3. Other name……..
–Pentose Phosphate Pathway
–Dickens-Horecker pathway
–Phosphogluconate pathway
–Shunt pathway
Hexose Monophosphate Shunt

4. ▪ About 10% of glucose/day are entered in
this pathway.
▪ In liver & RBCs, it is 30%.
▪ The purpose of this pathway is generation
of…..
–Reduced NADPH
–Pentose phosphate (for nucleotide
synthesis)
Hexose Monophosphate Shunt

5. ▪ The enzymes of HMP shunt are located in the
Cytosol.
▪ Following tissues are highly active in HMP pathway…
– Liver
– Adipose tissue
– Adrenal gland
– RBCs
– Testes
– Lactating mammary gland.
▪ Most of these tissues are involved in fatty acids &
steroids biosynthesis which depends on NADPH
Location of pathway

6. Overview of the shunt pathway
▪ It has two phases
–Oxidative phase
–Non-oxidative phase
▪ During oxidative phase, glucose-6-phosphate
is oxidized with generation of 2 moles of
NADPH, and one mole of pentose phosphate,
with liberation of one mole of CO2.
▪ During non-oxidative phase, pentose
phosphate is converted to intermediates of
glycolysis.

7. Oxidative phase
Glucose 6-phosphate
6-phosphogluconolactone
6-phosphogluconate
Ribulose 5-phosphate
Glucose 6-phosphate
dehydrogenase
Gluconolactone
hydrolase
Phoshogluconate
dehydrogenase
NADP+
NADPH+H+
NADP+
NADPH+H+
Mg+
CO2
H2O

8. Xylulose 5-phosphate Ribose 5-phosphate
Sedoheptulose
7-phosphate
Glyceraldehyde
3-phosphate
Erythrose
4-phosphate
Fructose
6-phosphate
Glyceraldehyde
3-phosphate
Fructose
6-phosphate
Fructose 6-phosphate
Ribulose 5-phosphate
Ribulose 5-p
epimerase
Ribose 5-p
ketoisomerase
Transketolase
TPP
TPP
Transketolase
Transaldolase
Reversal of
Glycolysis
Non-Oxidative phase
Glucose 6-phosphate
(5C)
(5C)(5C)
(3C)
(7C)
(4C) (6C)
(3C)
(6C)
(6C)
(6C)

9. Reactions of the pathway
▪ The sequence of reactions of HMP
shunt are divided into……
– Oxidative phase
– Non – oxidative phase

10. Oxidative phase
▪ Glucose 6-phoshate dehydrogenase (G6PD)
is an NADP-dependent enzyme that converts
G6P to 6-phosphogluconolactone.
▪ Here reducing equivalents are accepted by
NADP
▪ Here one molecule of NADPH+H+ is generated.
▪ This is rate limiting step in this pathway.
▪ 6-phosphogluconolactone is hydrolysed to 6-
phosphogluconate by the enzyme gluconolactone
hydrolase.

11. 6-phosphogluconate dehydrogenase
▪ dehydrogenate 6-phosphogluconate to 3
keto 6-phosphogluconate which is
spontaneously undergoes decarboxylation
to give ribulose 5-phosphate.
▪ Here 1 C of 6-phosphogluconate is
removed as CO2.
▪ Here 2nd molecule of NADPH+H+ is
generated.

12. Non-Oxidative phase
▪ This phase is concerned with the interconversion
of 3, 4, 5 & 7 “C” monosaccarides.
▪ Ribulose 5-P. is acted upon by an epimerase to
produce xylulose 5-P.
▪ Ribulose 5-P. is converted to ribose 5-P by
ketoisomerase.
▪ The enzyme transketolase catalyses the
transfer of 2 “C” from xylulose 5-P to ribose
5-P to give 3 “C” glyceraldehyde 3-P and a 7
“C” Sedoheptulose 7-P.
▪ Transketolase is depends on the coenzyme
thiamine (TPP) & Mg+.

13. ▪ Transaldolase transfer the 3 “C” fragment
from Sedoheptulose 7-P to glyceraldehyde
3-P to give fructose 6-P and 4 “C” erythose
4-P.
▪ The enzyme transketolase catalyses the
transfer of 2 “C” from xylulose 5-P to
erythrose 4-P to generate fructose 6-P and
glyceraldehyde 3-P.
▪ fructose 6-P and glyceraldehyde 3-P can be
further catabolised through glycolysis and
TCA. Glucose may also be synthesized from
these two compounds.

14. Summary of HMP Shunt
▪ For complete oxidation of glucose 6-
phosphate to 6CO2 , we have to start with
6 mole. of glucose 6-phosphate. Of these
6, 5moles are regenerated with production
of 12 NADPH.
6 Glucose 6-phosphate + 12 NADP++6 H2O
6 CO2+ 12 NADPH+H++ 5 Glucose 6-phosphate

15. Regulation of HMP Shunt
▪ The rate limiting step in HMP shunt is the
reaction catalyzed by glucose 6-phosphate
dehydrogenase (G6PD).
▪ G6PD is regulated in two ways…
– Allosteric regulation- by availability of Substrate
(NADP+)
– Hormonal regulation- Insulin

16. Significance of HMP Shunt
▪ HMP Shunt is unique in generation……
– Pentoses
– NADPH
▪ These are needed for biosynthetic
pathways.
▪ And for other functions.

17. Importance of Pentoses
▪ In the HMP Shunt, hexoses are converted into
Pentoses.
▪ Most important pentose is ribose 5- phosphate
▪ This pentose and its derivatives are useful in….
– The synthesis of Nucleic acids(DNA & RNA)
– Nucleotides (ATP, NAD+, FAD, & CoA)

18. Importance of NADPH
▪ NADPH is required for the biosynthesis of
fatty acids & steroids. (hence HMP shunt is
more active in the tissues concerned with
lipogenesis e.g. adipose tissue, liver)
▪ Used in the synthesis of certain amino acids
involving glutamate dehydrogenase.
▪ Detoxification of drugs and foreign compound by
cytochrome P450 requires NADPH.
▪ NADPH is required for the process called
phagocytosis.
▪ NADPH is essential to maintain the integrity of
RBC membrane and to keep iron in ferrous state.

19. ▪ Used in the detoxification of H2O2 with the
help of glutathione, as follows……
H2O2
2 H2O G-S-S-G
2GSH
NADP+
NADPH+H+
Glutathione
peroxidase
Glutathione
reductase
(oxidized)
(reduced)

20. Glucose 6-phosphate dehydrogenase
deficiency
▪ G6PD deficiency is an inherited sex-linked
trait.
▪ Deficiency seen in all the cells of the body,
but more severe in RBC.
▪ In RBCs, HMP shunt is the only means of
providing NADPH.
▪ activity of G6PD impairs synthesis of
NADPH in RBCs.
▪ This results in accumulation of methemoglobin
& peroxide in RBC leading to hemolysis.

21. Clinical manifestations in G6PD
deficiency
▪ Most of the patients with G6PD
deficiency do not show any clinical
symptoms.
▪ Some of them, develop hemolytic anemia
if they administered oxidant drugs or
exposed to severe infection.
▪ The drugs such as primaquine
(antimalarial), acetanilide (antipyretic),
etc

22. Wernicke-Korsakoff syndrome
▪ Genetic disorder associated with HMP
shunt.
▪ An alteration in transketolase activity
that reduces its affinity with TPP.
▪ The symptoms are……
– Mental disorder
– Loss of memory
– Partial paralysis.

23. Contact
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Ashok Katta
Address
Asst. Professor
Dept. Of Biochemistry
Dhanalakshmi Srinivasan Medical
College, Siruvachur,
Perambalur - 621212