Hexose Mono Phosphate (HMP) Shunt

Hexose mono phosphate
(HMP) shunt
Pentose phosphate pathway

Pentose ribose is produced in this pathways
Direct oxidative pathway

An alternate route for the metabolism of glucose
No ATPs are produced

This pathway produces
NADPH + H+
Pentose sugars
HMP shunt
Site :
Pathway is active in adrenal gland, liver,
testis, adipose tissue, thyroid, ovary, lactating
mammary gland, erythrocytes
Its activity is low in non-lactating mammary
gland and skeletal muscle
Sub site:
All enzymes of this pathway are found in
cytosol
Pathway is different from glycolysis that, here

glucose undergoes oxidation and liberate CO 2 &
generates NADPH
Thus pathway accounts for complete oxidation of
glucose
It is a multi-cyclic process in which 3

molecules of Glucose 6-P give rise to 3
molecules of CO2 and 3 five carbon
sugars
3 five carbon sugars are rearranged to
generate 2 molecules of G-6-P and 1
molecule of glyceraldehyde 3-P
Reactions of HMP shunt are divided into

two phases
Oxidative phase (irreversible)
Non-oxidative phase (reversible)
In the oxidative phase,

Glucose 6-P undergoes dehydrogenation and
decarboxylation &
forms Ribulose 5-phosphate (5C), 2 NADPH+ H+
and CO2
A. Oxidative phase of HMP shunt
Mg++ or Ca++
Glucose 6-phosphate
dehydrogenase
Glucose 6-phosphate dehydrogenase = G6PD
+ H+
Mg++, Mn++, Ca++
Gluconolactone
hydrolase
Mg++, Mn++, Ca++

6-phosphogluconate
dehydrogenase
Thus oxidative phase generates

2 molecules of NADPH + H+
One Ribulose 5-phosphate (5C)
One CO2
B. Non oxidative phase of HMP shunt
In this phase, Ribulose 5-phosphate is

rearranged to form glucose 6-phosphate
This phase also generates ribose precursors
3CO2
3
Transketolase
Transaldolase
Transketolase
Regulation
Enzyme
Activity in
fed state
Activity in
Inducer
starvation
and diabetes
Glucose 6phosphate
dehydrogenase
Insulin
6-phosphogluconate
dehydrogenase
Insulin
Significances of HMP shunt
1.
Provides reducing equivalents (NADPH) which are used in the

synthesis of
Fatty acids (eg. In Adipose tissue, lactating mammary gland,

liver)
Steroids (eg. In testis, adrenal cortex etc)
Glutamate (via Glutamate dehydrogenase reaction in liver)
Thyroid hormones (thyroid)
Reduced glutathione (important in erythrocytes)
2. Provides ribose sugars for nucleotide and

nucleic acid synthesis
Ribose 5-P reacts with ATP to form PRPP
and this is used in nucleotide biosynthesis
3. Role in protecting RBC membranes
RBCs are rich in Glutathione
Reduced glutathione removes H2O2 from the erythrocytes catalyzed by

glutathione peroxidase
GSH GS-SG
NADPH produced from HMP shunt is used for the reduction of oxidized
glutathione
This reaction is catalyzed by glutathione reductase
Significance (contd.)
Glutathione
peroxidase
G-S-S-G
NADPH + H+
HMP
shunt
2H
Se
FAD
2 G-SH
NADP+
Glutathione
reductase
2H2O
H2O2
RBCs
H2O2 may decrease the life span of RBCs by increasing

the rate of oxidation of hemoglobin (Fe ++) to methemoglobin
(Fe+++).
GSH reduces oxidized Hb to reduced form
GSH decomposes H2O2
Impairment in HMP shunt leads to hemolysis of RBCs
(deficiency of G-6-PD)
G-6-PD deficiency
Deficiency in G-6-PD leads to increased susceptibility of
RBCs to hemolysis
Babies born with this genetic disease are sensitive to
antimalarial drugs (eg. Primaquine) or drugs like aspirin,
sulfadrugs etc
These drugs necessitates high GSH concentration
In susceptible individuals ingestion of these drugs cause
hemolysis
Favism
In the susceptible (or G-6-PD deficient)
individuals, eating fava beans --> induces
hemolytic anemia --> called favism
Fava beans are implicated in inducing an anemic

response in G-6-PD deficient individuals
Fava bean ( Broad bean, faba bean,

horse bean, field bean, tic bean)
The compounds Vicine and Isouramil, are

abundant in fava beans, are hypothesized to be
the causative agents for the hemolytic response
Inhaling the pollens of fava bean plant can also
induce hemolysis in favic individuals
Differences between
Glycolysis
HMP shunt
Produces ATP
No ATP
No release of CO2
Release of CO2
NADH is generated & used for

energy production
NADPH is produced & used for

reductive synthesis
Produces triose phosphates
Produces pentose phosphates
No complete oxidation
Accounts for complete oxidation

Hexose Mono Phosphate (HMP) Shunt

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Hexose Mono Phosphate (HMP) Shunt

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Hexose mono phosphate

Pentose phosphate pathway

Direct oxidative pathway

No ATPs are produced

Pathway is different from glycolysis that, here

It is a multi-cyclic process in which 3

Reactions of HMP shunt are divided into

In the oxidative phase,

A. Oxidative phase of HMP shunt

Glucose 6-phosphate dehydrogenase = G6PD

Mg++, Mn++, Ca++

Thus oxidative phase generates

B. Non oxidative phase of HMP shunt

In this phase, Ribulose 5-phosphate is

Significances of HMP shunt

Provides reducing equivalents (NADPH) which are used in the

Fatty acids (eg. In Adipose tissue, lactating mammary gland,

Steroids (eg. In testis, adrenal cortex etc)

Glutamate (via Glutamate dehydrogenase reaction in liver)

Thyroid hormones (thyroid)

Reduced glutathione (important in erythrocytes)

2. Provides ribose sugars for nucleotide and

3. Role in protecting RBC membranes

RBCs are rich in Glutathione

Reduced glutathione removes H2O2 from the erythrocytes catalyzed by

This reaction is catalyzed by glutathione reductase

H2O2 may decrease the life span of RBCs by increasing

Fava beans are implicated in inducing an anemic

Fava bean ( Broad bean, faba bean,

The compounds Vicine and Isouramil, are

NADH is generated & used for

NADPH is produced & used for

Produces triose phosphates

Produces pentose phosphates

Accounts for complete oxidation

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