Hexose Mono Phosphate pathway

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HMP Shunt
Pathway

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Presented By
Muhammad Mueez
Department of
Human Genetics & Molecular Biology
University of Health Sciences, Lahore

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o Introduction
o Site of Reaction
o Summary
o Steps
 Oxidative Reactions
 Non-Oxidative Reactions
o Importance and Uses.
Table of Contents

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Introduction
Pentose Phosphate Pathway:
Also known as Hexose Mono-
Phosphate [HMP] Shunt, Phosphogluconate pathway and Direct
Oxidative Pathway.
The glycolytic and citric acid cycle are concerned with the oxidation
of most of the Glucose about 90%. While there are other pathways
for the rest of the glucose metabolism and are very important in
cell’s, these includes HMP Shunt and glucuronic acid pathway.

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 Occurs in cytosol of cells.
 Not all cells have these shunts
or path ways.
 Liver Cells, Adrenal gland cells,
mammary gland cells, Testes &
Ovaries, erythrocytes, eyes cells
and adipose tissue.

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■ It includes irreversible oxidative reactions.
■ Followed by a series of reversible sugar–phosphate
interconversions
Summary Of HMP Shunt

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Stimulation
 The HMP shunt pathway is under the regulation of
the demands of NADPH in the respective tissue.
 The rate-limiting enzyme is G6PD and has allosteric
inhibition directed by the presence of NADPH and
allosteric activation via the presence of NADP+.

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Oxidative Reactions
The oxidative portion of the pentose phosphate pathway consists
of three reactions that lead to the formation of ribulose 5-
phosphate, CO2, and two molecules of NADPH for each molecule
of glucose 6-phosphate oxidized.
Glucose 6-phosphate + 2 NADP+ + H20
Ribose 5-phosphate + CO2 + 2NADPH + 2H+

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STEP - 1
Glucose 6-phosphate, is converted
into 6-Phospho-gluconolactone.
The enzyme G6PD plays major role
here, and its deficiency may lead to
disastrous effects on cells.
NADP+ is reduced to NADPH

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STEP - 2
6-Phosphogluconolactone is
hydrolyzed by Lactonase.
 The reaction is irreversible

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STEP - 3
 The oxidative decarboxylation of the product,
6-phosphogluconate, is catalyzed by 6
phosphogluconate dehydrogenase.
 This irreversible reaction produces a pentose
sugar–phosphate (ribulose 5-phosphate),
CO2 (from carbon 1 of glucose), and a
second molecule of NADPH

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STEP - 4
Isomerism of Ribulose 5-phosphate
into Ribose 5-phosphate,by enzyme
phoshopentose isomerase.
In some cells, reactions stops here
and end product is recycled.

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Non-Oxidative Reactions
● The nonoxidative reactions of the pentose phosphate pathway
occur in all cell types synthesizing nucleotides and nucleic
acids.
● These reactions catalyze the interconversion of sugars
containing three to seven carbons
● These reversible reactions permit ribulose 5-phosphate to be
converted either to ribose 5-phosphate or to intermediates of
glycolysis .

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Enzymes
Transketolase
Catalyzes the
transfer of a two
carbon fragment
from a ketose
donor to an aldose
acceptor. Co factor
TPP is required for
stabilization
Transaldolase
Catalyzes a reaction
similar to the
aldolase reaction of
glycolysis: a three-
carbon fragment is
removed

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● In this non-oxidative phase, ribulose 5-phosphate is
first epimerized to xylulose 5-phosphate
STEP-1

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● Transketolase transfers C-1 and C-2 of xylulose 5-phosphate to
ribose 5-phosphate, forming the seven-carbon product
sedoheptulose 7-phosphate
● The remaining 3 carbon fragment from xylulose is
glyceraldehyde 3-phosphate
STEP-2

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● A three-carbon fragment is removed by Transaldolase from
sedoheptulose 7-phosphate and condensed with
glyceraldehyde 3-phosphate, forming fructose 6-phosphate
and the tetrose erythrose 4-phosphate
STEP-3

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● Now transketolase acts again, forming fructose 6-
phosphate and glyceraldehyde 3-phosphate from erythrose
4-phosphate and xylulose 5-phosphate
STEP-4

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Inhibitation
and moves to Glycolysis

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Importance
Production of NADPH:
The main goal of HMP shunt is to produce NADPH
from NADP+.
Reduction Of Glutathione:
Reduced Glutathione help to remove Free Radical
and Peroxides form cell.
Reduce Oxidative Stress:
Free Radical produces oxidative stress in cell and
cause cell damage and diseases, reduced by Glutathione.

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Other Significances
Formation of Pentoses
Only pathway to reduce NADP+, also the regeneration of –SH group.
Importance in RBCs
Ribose 5-phosphate + ATP 5- Phosphoribosyl-1-pyrophosphate [PRPP]
PRPP is used for biosynthesis of purines; Adenine and Guanine.
De Novo synthesis of Purines
Need for formation of nucleosides,nucleotides, ATP and many other
Co-enzymes

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