HMP Shunt

HMP Shunt
Hexose monophosphate pathway or HMP shunt is also called pentose phosphate pathway
or phosphogluconate pathway. This is an alternative pathway to glycolysis and TCA cycle for
the oxidation of glucose. However, HMP shunt is more anabolic in nature, since it is concerned
with the biosynthesis of NADPH and pentoses.
HMP Shunt- A Unique Multifunctional Pathway
The pathway starts with glucose 6-phosphate. As such, no ATP is directly utilized or
produced in HMP pathway. It is a unique multifunctional pathway, since there are several
interconvertible substances produced which may proceed in different directions in the metabolic
reactions.
Location
The enzymes of HMP shunt are located in the cytosol. The tissues such as liver, adipose
tissue, adrenal gland, erythrocytes, testes and lactating mammary gland, are highly active in
HMP shunt.
Reactions
The sequence of reactions of HMP shunt is divided into two phases-oxidative and non-
oxidative.
1. Oxidative phase: Glucose 6-phosphate dehydrogenase (G6PD) is an NADP-dependent enzyme
that converts glucose 6-phosphate to 6-phosphogluconolactone. The latter is then hydrolysed by
the gluconolactone hydrolase to 6-phosphogluconate. The next reaction involving the synthesis
of NADPH is catalysed by 6-phosphogluconate dehydrogenase to produce 3 keto 6-
phosphogluconate which then undergoes decarboxylation to give ribulose 5 -phosphate.
G6PD regulates HMP shunt: The first reaction catalysed by G6PD is most regulatory in
HMP shunt. This enzyme catalyses an irreversible reaction.
2. Non-oxidative phase: The non-oxidative reactions are concerned with the interconversion of
three, four, five and seven carbon monosaccharides. Ribulose 5 –phosphate is acted upon by an
epimerase to produce xylulose 5-phosphate while ribose 5 –phosphate ketoisomerase converts
Ribulose 5 –phosphate to ribose 5-phosphate.
The enzyme transketolase catalyses the transfer of two carbon moiety from xylulose 5-
phosphate to ribose 5-phosphate to give a 3 carbon glyceraldehyde 3-phosphate and a 7 carbon
sedoheptulose 7-phosphate. Transketolase is dependent on the coenzyme thiamine
pyrophosphate (TPP) and Mg2+ ions. Transaldolase brings about the transfer of a 3-carbon
fragment (active dihydroxyacetone) from sedoheptulose 7-phosphate to glyceraldehyde 3-
phosphate to give fructose 6-phosphate and four carbon erythrose 4-phosphate. Transketolase
acts on xylulose 5-phosphate and transfers a 2-carbon fragment (glyceraldehyde) from it to
erythrose 4-phosphate to generate fructose 6-phosphate and glyceraldehyde 3-phosphate.
Fructose 6-phosphate and glyceraldehyde 3-phosphate can be further catabolized through
glycolysis and citric acid cycle. Glucose may also be synthesized from these two compounds.
For the complete oxidation of glucose 6-phosphate to 6CO2, its starts with 6 molecules of
glucose 6 –phosphate. Of these 6, 5 moles are regenerated with the production of l2 NADPH.
The overall reaction may be represented as:
6 Glucose 6 -phosphate+ 12 NADP+ + 6H2O 6CO2 +12 NADPH + 12H+ + 5 Glucose 6-
phosphate.
Significance of HMP Shunt
HMP shunt is unique in generating two important products-pentoses and NADPH needed
for the biosynthetic reactions and other functions.
Importance of Pentoses
In the HMP shunt, hexoses are converted into pentoses, the most important being ribose
5-phosphate. This pentose or its derivatives are useful for the synthesis of nucleic acids (RNA
and DNA) and many nucleotides such as ATP, NAD+, FAD and CoA.
Skeletal muscle is capable of synthesizing pentoses, although only the first few enzymes
of HMP shunt are active. It, therefore, appears that the complete pathway of HMP shunt may not
be required for the synthesis of pentoses.
Importance of NADPH
1. NADPH is required for the reductive biosynthesis of fatty acids and steroids, hence HMP
shunt is more active in the tissues concerned with lipogenesis, eg. Adipose tissue, liver etc.
2. NADPH is used in the synthesis of certain amino acids involving the enzyme glutamate
dehydrogenase.
3. There is a continuous production of H2O2 in the living cells which can chemically damage
unsaturated lipids, proteins and DNA. This is, however, prevented to a large extent through
antioxidant reactions involving NADPH. Glutathione mediated reduction of H2O2 is given in
the next column.
Glutathione (reduced, GSH) detoxifies H2O2, peroxidase catalyses this reaction. NADPH
is responsible for the regeneration of reduced glutathione from the oxidized one.
4. Microsomal cytochrome P450 system (in liver) brings about the detoxification of drugs and
foreign compounds by hydroxylation reactions involving NADPH.
5. Phagocytosis is the engulfment of foreign particles, including microorganisms, carried out by
white blood cells. The process requires the supply of NADPH.
6. Special functions of NADPH in RBC: NADPH produced in erythrocytes has special
functions to perform. It maintains the concentration of reduced glutathione (reaction explained in
3) which is essentially required to preserve the integrity of RBC membrane. NADPH is also
necessary to keep the ferrous iron (Fe2+) of hemoglobin in the reduced state so that accumulation
of methemoglobin (Fe3+) is prevented.

HMP Shunt

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