Pentose phosphate pathway (Hexose Monophosphate Pathway)

Pentose phosphate pathway is an alternative pathway to glycolysis and TCA cycle for oxidation of glucose. It is a shunt of glycolysis. It is also known as hexose monophosphate (HMP) shunt or phosphogluconate pathway. It occurs in cytoplasm of both prokaryotes and eukaryotes. While it involves oxidation of glucose, its primary role is anabolic rather than catabolic. It is an important pathway that generates precursors for nucleotide synthesis and is especially important in red blood cells (erythrocytes).

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 ofglucose, its
primary role isanabolicrather thancatabolic.

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 shuntis useful in adipose tissue, liver,
erythrocytes, testes, adrenal glands and lactating mammary glands.
The HMP generates NADPH for reductivebiosynthesisof lipids,
andribosefornucleotideandnucleic acidbiosynthesis.

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
theoxidativephase, in
which NADPH is generated
The second is the non-
oxidativesynthesisof
5-carbon sugars.

5. Oxidativephase

7. This phase starts with the
oxidation of glucose 6-
phosphateby the
enzymeglucose 6-phosphate
dehydrogenaseto yield6-
phosphoglucono-δ-lactone.
This enzyme is an NADP
dependent enzyme, where
NADP
+
accepts an electron to
formNADPH+ H
+
.
The product6-
phosphoglucono-δ-
lactonethen gets hydrolyzed
to6-phosphogluconateby a
specific enzymelactonase

8. The product obtained from the
previous reaction i.e
6-phosphogluconategets
decarboxylated and oxidized to
giveD-ribulose 5-phosphateand
alsoNADPH + H
+
is produced once
more. This reaction was catalyzed by
the enzyme6-phosphogluconate
dehydrogenase.
The final step of the oxidative
phase is the conversion
ofribulose 5-phosphateto its
isomerribose 5-phosphateby
the enzymephosphopentose
isomerase.

9. Non-Oxidative Phase

11. Oxidative reactions is followed by a series reversible sugar phosphate inter-conversion
reaction.
Ribulose-5-phosphateis
epimerized to
producexylulose 5-
phosphatein 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
formsedoheptulose-7-
phosphateandglyceralde
hyde 3—phosphate.

12. Sedoheptulose -7-phosphate
transfer three carbon moiety
to glyceraldehyde -3-
phosphate to formfructose 6-
phopsphateanderythrose 4-
phosphatein 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 reducednicotinamide
adenine dinucleotide phosphate(NADPH), a
cofactor inglutathionemetabolism 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.