Pentose Phosphate Pathway (

HMP)
MLS 218
Objectives
To understand the function of the pentose
phosphate pathway In production of
NADPH and precursors for nucleic acid
synthesis.
Introduction
In most animal tissues, glucose is catabolized via
the glycolytic pathway into two molecules of
pyruvate. Pyruvate is then oxidized via the citric
acid cycle to generate ATP.
There is another metabolic fate for glucose
used to generate NADPH and specialized
products needed by the cell. This pathway is
called the pentose phosphate pathway also
called as the hexose monophosphate shunt
(HMP shunt), or the phosphogluconate
pathway.
Cont..
 The pentose phosphate pathway produces NADPH
which is the universal reductant in anabolic pathways.
 In mammals the tissues requiring large amounts of
NADPH produced by this pathway are the tissues that
synthesize fatty acids and steroids such as the
mammary glands, adipose tissue, adrenal cortex and the
liver.
 Tissues less active in fatty acid synthesis such as
skeletal muscle are virtually lacking the pentose
phosphate pathway.

 The second function of the pentose phosphate

pathway is to generate pentoses, particularly ribose
which is necessary for the synthesis of nucleic acids.
Cont…
The pentose phosphate pathway has two
distinct phases:
the oxidative phase , which produces
NADPH and the pentose ribulose-5-
phosphate ;
the rearrangement phase ( non oxidative
phase ), which rearranges pentose phosphates
into Triose and hexose phosphates , which
can be returned to the normal glycolysis
sequence
Summary of HMP pathway
Regulation
The first reaction is the irreversible and is the
committed step
This reaction is catalyzed by glucose -6 –
phosphate dehydrogenase and is allosterically
regulated
This enzyme is inhibited at high concentrations
of NADPH
G6PD deficiency

 Mutations present in some populations causes a deficiency in

glucose 6 ‐ phosphate dehydrogenase, with consequent impairment
of NADPH production.

 Reduced glutathione (GSH) protects the cell by destroying

hydrogen peroxide and hydroxyl free radicals. Regeneration of GSH
from its oxidized form (GS‐SG) requires the NADPH

 Detoxification Of H2O2 is inhibited, and cellular damage results ‐

leads to erythrocyte membrane breakdown and hemolytic anemia.

 Most G6PD ‐ deficient individuals are asymptomatic ‐ only in

combination with certain environmental factors (sulfa antibiotics,
herbicides, antimalarials, *divicine)do clinical Manifestations occur.