HMP pathway and its significance

Alina George | Mam Yad-e-Baiza Nawal | Govt. Post Graduate College

 HMP SHUNT PATHWAY

• DEFINITION:

It is a metabolic pathway parallel to glycolysis. It generates NADPH and

pentoses essential in body for various reasons.

• WHY HMP PATHWAY IS CALLED SHUNT?

It is called HMP SHUNT PATHWAY because the pathway allows for carbon
atoms from glucose-6-phosphate to take a brief detour (shunt) before they
proceed down the glycolytic pathway.

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 HMP Pathway

• Phospho gluconate pathway

• Pentose phosphate pathway

• Hexose monophosphate pathway

• 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:

1. NADPH

2. Pentoses

• Not directly meant for energy production

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 • ORGANS?TISSUES

• Rapidly dividing cells and in tissues where there is a

great requirement of NADPH such as:

• Liver

Where does this • Adipose tissue

pathway take place?
• Adrenal cortex

• Gonads

• Lens

• RBC’s

• The pathway is less active in the skeletal muscle.

 HMP Pathway

• All the reactions of this pathway take place in the cytoplasm.

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HMP pathway an overview
 HMP
Pathway

Oxidative Non-
phase Oxidative
Phase

Pentoses Glycolytic
NADPH
intermediates

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 • Oxidative phase leads to formation of
Ribose 5-P by oxidative decarboxylation

• Non oxidative phase rearrangement

process results in the formation of
glycolytic intermediates

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Oxidative phase
  
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 STEP-1:

•  

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 STEP-2:

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 STEP-3:

• The product 6-
phosphogluconate
gets
decarboxylated to
give D-ribulose 5-
phosphate.

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Non-Oxidative phase
 • Reactions of HMP
pathway – Non-
Oxidative phase
• Ribulose 5-phosphate 3-
epimerase(Phosphopentose
epimerase) alters the
configuration about carbon 3,
forming the epimer Xylose 5-
phosphate, also a
ketopentose
• Ribose 5-phosphate keto
Isomerase
(phosphopentose
isomerase) converts
Ribulose 5-phosphate to the
corresponding aldopentose,
ribose 5-phosphate

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 Non-Oxidative phase

• The pathway catalyzes the interconversion of: 3,4,5,6 and 7 carbon sugars
in a series of non oxidative reactions

• That can result in the synthesis of:

• 5-carbon sugars for nucleotide biosynthesis or

• Degradation of excess 5-carbon sugars into intermediates of the glycolytic

pathway.

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 Rearrangement of sugars in the Non-Oxidative
Phase

• C5+C5 C3+C7

• C3+C7 C6+C4

• C5+C4 C3+C6

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 STEP-1-Non-Oxidative phase

C5+C5 C3+C7
• Transketolase
catalyzes the transfer
of 2-carbon unit of
ketose to aldehydic
carbon of aldose
sugar.
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 STEP-1 Non-oxidative phase

•  

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 STEP-2-Non-Oxidative phase

C3+C7 C6+C4
• Transaldolase catalyzes
the transfer of 3-carbon
unit from
ketosedoheptulose-7-
phosphate onto aldose
glyceraldehyde 3-
phosphate.
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 STEP-3-Non-Oxidative phase

C5+C4 C3+C6
• Transketolase catalyzes
the reaction
• Xylose 5- phosphate
again serves as a donor
of glycoaldehyde
• Erythrose 4-phosphate
is the acceptor.
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Significance of HMP pathway
 Major outcomes

•  

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 Significance of NADPH

Fatty acids
• It is used for reductive
biosynthesis
Reduction of
• For maintenance of glutathione
cholesterol

membrane integrity of red

blood cell and lens,
detoxification and NADPH
macrophageal functions

Sphingolipids detoxification

Steroids
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 Significance of pentoses

Nucleic acids

Glycoproteins pentoses ATP

Coenzymes
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 NUCLEOTIDES:

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 ATP:

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 COENZYMES:

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NADP FAD 03/17/2020
 Utilization of Pentoses

Dietary

Degradation Degradation Non-Oxidative phase of HMP

of of nucleic Pathway
coenzymes acids

pentoses

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 Significance of Glycolytic intermediates

• Glyceraldehyde-3-Phosphate and Fructose-6-Phosphate formed may enter

glycolysis for ATP synthesis or may be used as intermediates of pathway of
gluconeogenesis( metabolic process used to make sugars from non-
carbohydrate precursors)

• The Pentose Phosphate Pathway thus serves as an entry into Glycolysis for
both 5-carbon and 6-carbon sugars.

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•  

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 PYRUVATE TO OXALOACETATE:

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 ACETL CO-A TO MALONYL CO-A:

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 GAMMA CARBOXYLATION OF GLUTAMIC ACID:

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 PROPIONY CO-A TO METHYL MALONYL CO-A:

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 Clinical significance

• Glucose-6-phosphate dehydrogenase (GSPD) deficiency

• An X-linked disorder

• Asymptomatic or hemolytic anemia

• Anemia may be associated with hemoglobinemia(excess of hemoglobin in

blood plasma) and hemoglobinuria( excretion of free hemoglobin in urine)

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 Pathophysiology of hemolytic Anemia

• 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
pathway

• 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 deficiency

• Identification and discontinuation of the precipitating agent is critical in cases

of glucose-6-phosphate dehydrogenase(G6PD) deficiency

• Affected individuals are treated with oxygen and bed rest, which may afford
symptomatic relief

• Prevention of drug-induced hemolysis is possible in most cases by choosing

alternative drugs

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 THANKYOU FOR LISTENING…

• REFERENCES:
• www.slideshare.net 7th February,2020

• www.pharmaexchange.info 16th February, 2020

• www.ncbi.nlm.nih.gov/books/NBK551687/ 16th February ,2020

• www.watcut.uwaterloo.ca/webnotes/Metabolism/HMS.html

16th February ,2020

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