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HMP Pathway- A
SSR Medical College, Mauritius
Phospho gluconate pathway
Pentose phosphate pathway
Hexose monophosphate shunt [HMP shunt]
All the intermediates of this pathway are in the mono phosphate form contrary to
glycolysis where bisphosphate forms of intermediates are also there.
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What is the purpose of HMP pathway ?
• An alternative route for the metabolism of glucose
• What is the outcome ???
o Not directly meant for energy production.
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Where does this pathway take place ?
Rapidly dividing cells and in tissues where there is a great requirement of NADPH such as:
Lactating mammary gland
The pathway is less active in the skeletal
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• All the reactions
of this pathway
take place in the
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Oxidative phase leads to formation of
Ribose-5-P by oxidative decarboxylation
Non oxidative phase involves
rearrangement process results in the
formation of glycolytic intermediates
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Glycolysis V/S HMP pathway
Characteristics Glycolysis HMP pathway
Occurrence All cells of the body Active in liver, adipose tissue, adrenal cortex, thyroid, erythrocytes,
testis, and lactating mammary glands.
Coenzyme NAD + NADP+
CO2 production No CO2 production CO2 is produced.
Pentose production Pentoses are not produced Pentoses are produced.
Intermediates Intermediates can be in the
mono or bisphosphate forms
Intermediates are never in the bisphosphate form.
Energy ATP is utilized as well as
ATP is neither utilized nor produced.
Glycolytic intermediates may enter glycolytic pathway to produce
Energy production both in
aerobic and anaerobic
NADPH is required for reductive biosynthesis and Pentoses are
required for synthesis of coenzymes and nucleotides.
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Reactions of HMP pathway- Oxidative phase
Reactions of oxidative phase of HMP pathway- 2 molecules of NADPH and one of CO2 are produced in the
oxidative phase. 12/22/2016Namrata Chhabra, M.D. 9
Reactions of HMP
• Ribulose 5-phosphate 3-epimerase
(Phosphopentose epimerase) alters the
configuration about carbon 3, forming the
epimer Xylulose 5-phosphate, also a
• Ribose 5-phosphate keto Isomerase
(Phosphopentose isomerase) converts
Ribulose 5-phosphate to the corresponding
aldopentose, ribose 5-phosphate.
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• The pathway catalyzes the interconversion of :
• six, and seven-carbon sugars in a series of nonoxidative reactions
• that can result in the synthesis of
o five-carbon sugars for nucleotide biosynthesis or
o the degradation of excess five-carbon sugars into intermediates of the glycolytic pathway.
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Rearrangement of sugars in the Non-
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• Transketolase catalyzes the transfer of the two-
carbon unit comprising carbons 1 and 2 of a
ketose (from Xylulose 5-phosphate) to the
aldehyde carbon of an aldose sugar (ribose 5-
phosphate), producing the seven-carbon ketose
sedoheptulose 7-phosphate and the aldose
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Step-1- Non-Oxidative phase
• Transketolase effects the conversion of a ketose sugar into an aldose with
two carbons less and an aldose sugar into a ketose with two carbons more.
• The reaction requires Mg2+ and thiamine pyrophosphate (vitamin B1) as
• Clinical significance- R.B.C Transketolase activity is measured to diagnose
underlying thiamine deficiency.
• In thiamine deficiency Transketolase activity is reduced.
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Step-2- Non-Oxidative phase
• Transaldolase catalyzes the
transfer of a three-carbon
(carbons 1–3) from the ketose
sedoheptulose -7-phosphate onto
the aldose glyceraldehyde 3-
phosphate to form the ketose
fructose 6-phosphate and the
four-carbon aldose Erythrose 4-
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Step-3 Non-Oxidative phase
• In this reaction catalyzed
by transketolase, Xylulose 5-
phosphate again serves as a donor of
• In this case Erythrose 4-phosphate is
the acceptor, and the products of the
reaction are fructose 6-phosphate and
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Biological advantage of reversible reactions
• Since the reactions of non oxidative phase are irreversible, the glycolytic
intermediates can also rearrange to form pentoses.
• The sum of these reactions is:
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Degradation of excess Pentoses through HMP
• Xylulose 5-phosphate can be formed from ribose 5-phosphate, or vice versa, by the sequential action
of phosphopentose isomerase and phosphopentose Epimerase, therefore:
o Thus, excess ribose 5-phosphate formed by the pentose phosphate pathway can be completely converted into glycolytic
o Moreover, any ribose ingested in the diet can be processed into glycolytic intermediates by this pathway.
o The carbon skeletons of sugars can be extensively rearranged to meet physiologic needs.
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Complete oxidation of glucose
• 3 molecules of Glucose-6-P enter simultaneously in this pathway to produce 3
molecules of CO2, 6 NADPH , 2 fructose-6-P and one molecule of glyceraldehyde-
• 2 molecule of Fructose-6-P are converted to 2 molecule of Glucose-6-P
while Glyceraldehyde-3-P is presumed to be equivalent to half a molecule of
• Three carbons less are presumed to be lost as CO2.
• If 6 molecules enter at the same time then it would represent loss of 6 molecules of
CO2 equivalent to complete oxidation of one molecule of glucose.
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Significance of HMP Pathway
• Glycolytic intermediates
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NADPH is mainly used for reductive
biosynthesis. Additionally it is used for
maintenance of membrane integrity of red
blood cell and lens, detoxification and
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Significance of Pentoses
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Utilization of Pentoses
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Significance of Glycolytic intermediates
• Glyceraldehyde-3-P and fructose-6-Pformed from 5‐C sugar phosphates may
enter Glycolysis for ATP synthesis or may be used as intermediates of
pathway of gluconeogenesis.
• The Pentose Phosphate Pathway thus serves as an entry into Glycolysis for
both 5‐carbon & 6‐carbon sugars.
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Significance of CO2
• CO2 produced from this pathway can be utilized for CO2 fixation reactions,
• Pyruvate to Oxaloacetate
• Acetyl co A to Malonyl co A
• Propionyl co A to Methyl malonyl co A
• Gamma carboxylation of glutamic acid residues etc.
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• Glucose-6-phosphate dehydrogenase (G6PD) deficiency
• An X-linked disorder
• Asymptomatic or Hemolytic anemia
• Anemia may be associated with hemogobinemia and hemoglobinuria
• Acute HA can develop as a result of three types of triggers: (i) fava beans,
(ii) infections, and (iii) drugs like- Antimalarial, antibiotics, Antipyretics/
analgesics, sulfonamides etc.
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• Reduced glutathione (GSH), a tripeptide with a
free sulfhydryl group, is required to combat
oxidative stress and maintain the normal
reduced state in the cell.
• Oxidized glutathione (GSSG) is reduced by
NADPH generated by glucose 6-phosphate
dehydrogenase in the pentose phosphate
• Cells with reduced levels of glucose 6-
phosphate dehydrogenase are especially
sensitive to oxidative stress.
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Treatment of Hemolytic Anemia in G6PD
• Identification and discontinuation of the precipitating agent is critical in cases of glucose-6-
phosphatase dehydrogenase (G6PD) deficiency.
• Affected individuals are treated with oxygen and bed rest, which may afford symptomatic
• Prevention of drug-induced hemolysis is possible in most cases by choosing alternative
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1) Further reading