The Pentose Phosphate Pathway in Metabolism
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Introduction
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•
Alternative
route
for
the
metabolism of
glucose
•
Also
known
as
Hexose
Monophosphate
(HMP)
shunt
•
More
complex
pathway
than
glycolysis
•
It
helps
in
–
formation
of
NADPH
for
synthesis
of
fatty
acids,
steroids,
–
maintaining reduced
glutathione
for
antioxidant
activity
–
synthesis
of
ribose
for
nucleotide
and
nucleic
acid
formation
Pentose
Phosphate
Pathway
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•
Like
glycolysis
it
occurs in
cytosol
•
Oxidation
is
achieved
by dehydrogenation
using
NADP
+
,
not
NAD
+
•
Its
carried out
in 2
step:
–
Irreversible
oxidative
phase:
3 molecules
of
glucose-6-phosphate
give rise
to
3 molecules of
CO
2
and 3
5-carbon
sugars.
–
Reversible
nonoxidative
phase:
Rearranged
to
regenerate
2 molecules of
glucose-6 phosphate
and
1 molecule of the
glyceraldehyde-3
phosphate
Oxidative
phase
•
Dehydrogenation
of
glucose-6-
phosphate
to
6-
phosphogluconate
catalyzed
by
glucose 6-phosphate
dehydrogenase
•
Followed
by
hydrolysis
of
6- phosphogluconolactone
to
Ribulose-5-phosphate
catalyzed
by
6-phosphogluconate
dehydrogenase
•
Decarboxylation
follows
with
the
formation
of
the
ketopentose
ribulose-5-
phosphate
•
Both this
step
requires
NADP
+
as
hydrogen
acceptor
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Non-oxidative
Phase
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•
Ribulose-5-phosphate
is the
substrate
for
two
enzymes
–
Ribose-5-phosphate
ketoisomerase
:
ribulose
5-
phosphate
to
the
corresponding
ribose-5-
phosphate
-
used
for
nucleotide and
nucleic
acid
synthesis
–
Ribulose-5-phosphate 3-epimerase
:
alters
the
configuration
about
carbon
giving
xylulose
5-
phosphate
Non-oxidative
Phase
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•
Xylulose-5-phosphate
(5c)
and
Ribose-5-
phosphate
(5c)
reacts
to
give
Glyceraldehyde-
3-phosphate
(3c)
and
Sedoheptulose-7-
phosphate
(7c)
by
the enzyme
Transketolase
•
Glyceraldehyde-3-phosphate
(3c)
and
Sedoheptulose-7-phosphate
(7c)
is
acted
by
Transaldolase
to
give
Fructose-6-phosphate
and
Erythrose-4-phosphate
Non-oxidative
Phase
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•
Erythrose-4-phosphate
and
Xylulose-5-phosphate
reacts
in the
presence
of enzyme
Transketolase
to
give
Fructose-6-phosphate
and
Glyceraldehyde-3-
phosphate
–
Mg
2+
and
thiamin
diphosphate
(vitamin
B1) as
coenzyme
•
S
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s
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q
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n
t
l
y
F
r
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t
o
s
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-
6
–
p
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p
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a
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i
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i
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o
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i
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d
t
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G
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-
6
-
p
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p
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a
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P
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x
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s
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m
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a
s
e
•
Glyceraldehyde-3-phosphate
-
reversal
of
glycolysis
and the
gluconeogenic enzyme
fructose
1,6
bisphosphatase
or
it
proceeds to
glycolysis.
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Importance
of
NADPH
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•
Bio-synthesis
of
Fatty
acid
•
Certain
amino
acid
involving
the
enzyme
glutamate
dehydrogenase
•
Antioxidant
reaction
–
Glutathione
mediated
reaction
of
H
2
O
2
•
Detoxification
of drugs
–
cytochrome
P450
•
Phagocytosis
•
Integrity
of
RBC
membrane
Importance
of
Pentose
Sugar
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•
Ribose-5
phosphate
–
useful
for
the
synthesis
of
nucleic
acid
(RNA
and
DNA)
and
nucleotide
•
Skeletal
muscles
capable of
synthesizing
pentoses
CLINICAL
ASPECTS
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•
Genetic
defects
of
glucose-6-phosphate
dehydrogenase
•
impairment of
the
generation
of NADPH
- X
chromosome
•
Mediterranean
and
Afro-Caribbean
origin
•
red
cell
hemolysis
(hemolytic
anemia)
•
subjected
to oxidative
stress
–
Infection
–
Drugs such
as the
antimalarial primaquine,
and
sulfonamides
–
Fava
beans
-
favism
R
e
f
e
r
ences
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•
Harper's
Illustrated
Biochemistry,
30E
(2015)
•
Biochemistry
-
U.
Satyanarayan
and
U.
Chakrapani
3
rd
edition
•
Lehninger Principles
of
Biochemistry,
Fourth
Edition
-
David
L. Nelson,
Michael M.
Cox
•
Biochemistry
-
Garrett
And Grisham 2nd
Ed
1998
•
Biochemistry
Stryer
5
th
Edition
repost
•
Color
Atlas
of Biochemistry
2005
The Pentose Phosphate Pathway, also known as the Hexose Monophosphate shunt, is an alternative route for glucose metabolism that plays a crucial role in NADPH synthesis, fatty acid production, antioxidant activity, and nucleotide formation. This pathway involves oxidative and non-oxidative phases, resulting in the generation of important metabolites such as ribose-5-phosphate and xylulose-5-phosphate. Through a series of enzymatic reactions, glucose-6-phosphate is converted to various carbon sugars and ultimately contributes to the synthesis of essential biomolecules.
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Pentose Phosphate Pathway www.facebook.com/notesdent al
Introduction Alternative route for the metabolism of glucose Also known as Hexose Monophosphate (HMP) shunt More complex pathway than glycolysis It helps in formation of NADPH for synthesis of fatty acids, steroids, maintaining reduced glutathione for antioxidant activity synthesis of ribose for nucleotide and nucleic acid formation www.facebook.com/notesdental
Pentose Phosphate Pathway Like glycolysis it occurs in cytosol Oxidation is achieved by dehydrogenation using NADP+, not NAD+ Its carried out in 2 step: Irreversible oxidative phase: 3 molecules of glucose-6-phosphate give rise to 3 molecules of CO2 and 3 5-carbon sugars. Reversible nonoxidative phase: Rearranged to regenerate 2 molecules of glucose-6 phosphate and 1 molecule of the glyceraldehyde-3 phosphate www.facebook.com/notesdental
Oxidativephase Dehydrogenation of glucose-6- phosphate to 6- phosphogluconate catalyzedby glucose 6-phosphate dehydrogenase Followed by hydrolysis of 6- phosphogluconolactone to Ribulose-5-phosphatecatalyzed by 6-phosphogluconate dehydrogenase Decarboxylation followswith the formation of the ketopentose ribulose-5- phosphate Both this step requires NADP+as hydrogenacceptor www.facebook.com/notesdental
Non-oxidativePhase Ribulose-5-phosphate is the substrate for two enzymes Ribose-5-phosphate ketoisomerase: ribulose 5- phosphate to the corresponding ribose-5- phosphate - used for nucleotide and nucleic acid synthesis Ribulose-5-phosphate 3-epimerase: alters the configuration about carbon giving xylulose 5- phosphate www.facebook.com/notesdental
Non-oxidativePhase Xylulose-5-phosphate (5c) and Ribose-5- phosphate (5c) reacts to give Glyceraldehyde- 3-phosphate (3c) and Sedoheptulose-7- phosphate (7c) by the enzymeTransketolase Glyceraldehyde-3-phosphate (3c) and Sedoheptulose-7-phosphate (7c) is actedby Transaldolase to give Fructose-6-phosphate and Erythrose-4-phosphate www.facebook.com/notesdental
Non-oxidativePhase Erythrose-4-phosphate and Xylulose-5-phosphate reacts in the presence of enzyme Transketolase to give Fructose-6-phosphate and Glyceraldehyde-3- phosphate Mg 2+ and thiamin diphosphate (vitamin B1) as coenzyme Subsequently Fructose-6 phosphate is isomerisedto Glucose-6-phosphate by enzyme Phosphohexose isomerase Glyceraldehyde-3-phosphate - reversal of glycolysis and the gluconeogenic enzyme fructose 1,6 bisphosphatase or it proceeds to glycolysis. www.facebook.com/notesdental
Importance of NADPH Bio-synthesis of Fatty acid Certain amino acid involving the enzyme glutamatedehydrogenase Antioxidant reaction Glutathione mediated reaction of H2O2 Detoxification of drugs cytochromeP450 Phagocytosis Integrity of RBC membrane www.facebook.com/notesdental
Importance of Pentose Sugar Ribose-5 phosphate useful for the synthesis of nucleic acid (RNA and DNA) and nucleotide Skeletal muscles capable of synthesizing pentoses www.facebook.com/notesdental
CLINICALASPECTS Genetic defects ofglucose-6-phosphate dehydrogenase impairment of the generation of NADPH - X chromosome Mediterranean and Afro-Caribbeanorigin red cell hemolysis (hemolytic anemia) subjected to oxidativestress Infection Drugs such as the antimalarial primaquine, and sulfonamides Fava beans - favism www.facebook.com/notesdental
References Harper's Illustrated Biochemistry, 30E (2015) Biochemistry - U. Satyanarayan and U. Chakrapani 3rdedition Lehninger Principles of Biochemistry, Fourth Edition - David L. Nelson, Michael M.Cox Biochemistry - Garrett And Grisham 2nd Ed1998 Biochemistry Stryer 5th Editionrepost Color Atlas of Biochemistry 2005 www.facebook.com/notesdental
