Pentose Phosphate Pathway
Dr. Sooad Al-Daihan
Biochemistry department
Overview
 The
pentose
phosphate
pathway is also called Hexose
Monophosphate Shunt or
Phosphogluconate Pathway.
 It is an alternate route for the
oxidation of glucose without
direct
consumption
or
generation of ATP.
 It takes place entirely in the
cytoplasm.
Importance of pentose phosphate pathway :
 Generation of NADPH
- mainly used for reductive synthesis
of fatty acids, cholesterol and
steroid hormones.
- hydroxylation
reaction
in
metabolism of phenylalanine and
tryptophan.
- production of reduced glutathione
in erythrocytes and other cells.
 Production of ribose residues
- used for nucleotide, nucleic acid ,
and coenzyme biosynthesis
 Serves as an entry into Glycolysis for
both 5‐carbon & 6‐carbon sugars.
The PPP is divided into two phases
 Oxidative non-reversible phase
-generates NAPDH
-Glucose 6-p undergoes dehydrogenation and
decarboxylation to give a pentose, ribulose
5-p, which is converted to its isomer, Dribose 5-p.
-Overall equation of 1st phase:
Glucose 6-p + 2 NADP++ H2O  ribose 5-p +
CO2 + 2 NADPH + 2 H+
 Non-oxidative reversible phase
-ribose 5‐P is converted back to Glucose 6-p by
a series of reactions involving especially two
enzymes
1. Transketolase :Transfer of the 2‐C fragment
2. Transaldolase :Transfer of the 3‐C fragment
Summary
Xylulose-5-p
Sedoheptulose-7-p
Ribose-5-p
Erythrose-4-p
Glyceraldehyde-3-p
Fructose-6-p
Importance of PPP in RBC
When erythrocytes are exposed to chemicals
that generate high levels of superoxide radicals,
GSH (Reduced Glutathione) is required to
reduce these damaging compounds
Glutathione Peroxidase catalyzes degradation
of organic hydroperoxides by reduction, as two
glutathione molecules are oxidized to a
disulfide GSSG
 The PPP is responsible for maintaining high
levels of NADPH in red blood cells for use as a
reductant in the glutathione reductase reaction.
Regulation of the pentose phosphate pathway
Glucose-6-P dehydrogenase (Rate
Limiting Reaction) is controlled by:
 Allosteric Regulation
-Feedback inhibited by NADPH
 Inducible enzyme
-The synthesis of glucose 6phosphate
dehydrogenase
is
induced
by
the
increased
insulin/glucagon ratio after a high
carbohydrate meal.
Glucose-6-phosphate dehydrogenase deficiency
causes hemolytic anemia
 Mutations present in some populations causes a deficiency in
glucose 6‐phosphate dehydrogenase, with consequent
impairment of NADPH production
 Detoxification of H2O2 is inhibited, and cellular damage
results ‐ lipid peroxidation 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.
*toxic ingredient of fava beans