The pentose phosphate pathway (PPP) is an alternative metabolic route to glycolysis for glucose oxidation, primarily serving anabolic processes by generating NADPH and ribose. It consists of two phases: the oxidative phase, which produces NADPH, and the non-oxidative phase, which synthesizes various sugar phosphates, leading to intermediates for glycolysis. Key regulatory enzymes include glucose-6-phosphate dehydrogenase, and deficiencies in the pathway, such as G6PD deficiency, can affect red blood cell function and are linked to resistance against malaria.

1. Pentose Phosphate Pathway
Anup Muni Bajracharya

2. Pentose phosphate pathway
• an alternative pathway to glycolysis and TCA
cycle for oxidation of glucose.
• also known as hexose monophosphate (HMP)
shunt or phosphogluconate pathway.
• a shunt of glycolysis
• occurs in cytoplasm of both prokaryotes and
eukaryotes
• While it involves oxidation of glucose, its
primary role is anabolic rather than catabolic.

3. Hexose monophosphate pathway
The fate of glucose whether to undergo glycolysis or the hexose
monophosphate pathway is decided by the relative concentrations
of NADP+ and NADPH.
Hexose monophosphate shunt is useful in adipose tissue, liver,
erythrocytes, testes, adrenal glands and lactating mammary glands.
The HMP generates NADPH for reductive biosynthesis of lipids,
and ribose for nucleotide and nucleic acid biosynthesis.

4. Phases in the PPP pathway
• Pentose phosphate pathway starts with glucose
and it is a multi-steps reaction.
• There are two distinct phases in the pathway.
The first is
the oxidative phase, in
which NADPH is generated
The second is the non-
oxidative synthesis of
5-carbon sugars.

5. Oxidative phase

7. This phase starts with the
oxidation of glucose 6-
phosphate by the
enzyme glucose 6-phosphate
dehydrogenase to yield 6-
phosphoglucono-δ-lactone.
This enzyme is an NADP
dependent enzyme, where
NADP+accepts an electron to
form NADPH + H+.
The product 6-
phosphoglucono-δ-
lactone then gets hydrolyzed
to 6-phosphogluconate by a
specific enzyme lactonase

8. The product obtained from the
previous reaction i.e
6-phosphogluconate gets
decarboxylated and oxidized to
give D-ribulose 5-phosphate and
also NADPH + H+ is produced once
more. This reaction was catalyzed by
the enzyme 6-phosphogluconate
dehydrogenase.
The final step of the oxidative
phase is the conversion
of ribulose 5-phosphate to its
isomer ribose 5-phosphate by
the enzyme phosphopentose
isomerase.

9. Non-Oxidative Phase

11. Oxidative reactions is followed by a series reversible sugar phosphate inter-conversion
reaction.
Ribulose-5-phosphate is
epimerized to
produce xylulose 5-
phosphate in the presence of
enzyme phosphor pentose
epimerase. Similarly ribulose-
5-phosphate is also keto-
isomerized into ribose 5-
phosphate.
Xylulose-5-phsphate
transfer two carbon
moiety to ribose 5-
phospahate in the
presence of enzyme
transketolase to
form sedoheptulose-7-
phosphate and glyceralde
hyde 3—phosphate.

12. Sedoheptulose -7-phosphate
transfer three carbon moiety
to glyceraldehyde -3-
phosphate to form fructose 6-
phopsphate and erythrose 4-
phosphate in the presence of
enzyme transaldolase.
Transketolase enzyme
catalyse the transfer of
two carbon moiety from
Xylulose-5-phsphate to
erythrose-4- phosphate to
form fructose-6-phosphate
and glyceraldehyde-3-
phosphate.
Fructose-6-phosphate and glyceraldehyde-3-phosphate is later enter into glycolysis and
kreb’s cycle.

13. Regulation
• The regulatory enzymes of HMP shunt pathway
are glucose-6-phosphate dehydrogenase and 6-
phosphogluconate dehydrogenase.
• The synthesis of both enzymes are induced by
insulin in human.
• The entry of glucose-6-phosphate into the
Pentose Phosphate Pathway is controlled by the
cellular concentration of NADPH.
• So the oxidative phase is controlled by NADPH.
• The non-oxidative phase is controlled by
pentoses.

14. Glucose-6-Phosphate Dehydrogenase Deficiency
G6PD activity is essential to normal functioning of
the hexose monophosphate (HMP) shunt.
This pathway generates reduced nicotinamide
adenine dinucleotide phosphate (NADPH), a
cofactor in glutathione metabolism in human RBCs.
The HMP shunt is tightly coupled to glutathione
metabolism, which serves to protect RBCs from
oxidant injury.
Accordingly, a marked deficiency of G6PD leaves
the red cells vulnerable to oxidant damage.

15. Result

16. Significance of Pentose phosphate pathway
• HMP is only the cytoplasmic pathway that generates
NADPH
• NADPH is produced in this pathway acts as reducing agent
during biosynthesis of various molecules eg. Fatty acids.
• This pathway generates 3, 4, 5, 6 and 7 carbon compounds
which are precursors for biosynthesis of other molecules.
Eg nucleotides are synthesized from ribose-5-phsophate.
• PPP is very essential for cell lacking mitochondria (eg. RBCs)
for generation of NADPH.
• NADPH is also used to reduce (detoxify) hydrogen peroxide
in cell.
• Resistance to malaria in some Africans are associated with
deficiency of glucose-6-phosphate dehydrogenase enzyme
because malarial parasites depend upon HMP shunt to
reduce glutathione in RBCs.