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