The pentose phosphate pathway (PPP), also known as the hexose monophosphate shunt, is an alternative glucose metabolism pathway to glycolysis. It generates NADPH and pentoses through oxidative and non-oxidative phases. NADPH is important for biosynthesis of fatty acids and antioxidation, while pentoses such as ribose-5-phosphate are precursors for nucleic acid synthesis. Certain tissues like liver and red blood cells heavily utilize the PPP. A deficiency in glucose-6-phosphate dehydrogenase, the first enzyme in the oxidative phase, can cause hemolytic anemia upon exposure to oxidative drugs or foods.
2. CONTENTS
• Introduction
• Pentose phosphate pathwayPentose phosphate pathway
• Steps involved in PPP/ HMP
• Significance of PPP/ HMP
• Importance of NADPH
• References
CONTENTS
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3. INTRODUCTION
• Alternative route for the metabolism of glucose to glycolysis andTCA
cycle for the oxidation of glucose
• Also known as Hexose Monophosphate Pathway (HMP) shunt
or phosphogluconate pathway
• More complex pathway than glycolysis
• It helps in
-formation of NADPH for synthesis of fatty
-maintaining reduced glutathione
-synthesis of ribose for nucleotide and nucleic acid formation
INTRODUCTION
Alternative route for the metabolism of glucose to glycolysis andTCA
Hexose Monophosphate Pathway (HMP) shunt
More complex pathway than glycolysis
for synthesis of fatty acids,steroids,
glutathione for antioxidant activity
for nucleotide and nucleic acid formation
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4. • PPP is more anabolic in nature
• it is concerned with the biosynthesis of NADPH &
pentoses
• About 10% of glucose entering in this pathway/day
• the liver & RBC metabolise about 30% of glucose by this
pathway
• The enzymes are located in the cytosol.• The enzymes are located in the cytosol.
• The tissues such as liver, adipose tissue, adrenal gland,
erythrocytes, testes, lactating mammary glands, are highly
active in HMP shunt
• Most of this tissues are involved in biosynthesis of fatty
acids and steroids which are dependent on the supply of
NADPH.
more anabolic in nature
it is concerned with the biosynthesis of NADPH &
10% of glucose entering in this pathway/day
the liver & RBC metabolise about 30% of glucose by this
The enzymes are located in the cytosol.The enzymes are located in the cytosol.
The tissues such as liver, adipose tissue, adrenal gland,
erythrocytes, testes, lactating mammary glands, are highly
Most of this tissues are involved in biosynthesis of fatty
acids and steroids which are dependent on the supply of
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5. HMP /
• It starts with glucose 6-phosphate
• No ATP is directly utilized or produced in HMP shunt
• It is multifunctional pathway, several interconvertible substances• It is multifunctional pathway, several interconvertible substances
produced, which are proceed in different directions in the metabolic
reactions
• Reactions of pathway are divided into 2 phases = Oxidative & Non
oxidative phase
HMP / PPP
No ATP is directly utilized or produced in HMP shunt
It is multifunctional pathway, several interconvertible substancesIt is multifunctional pathway, several interconvertible substances
produced, which are proceed in different directions in the metabolic
Reactions of pathway are divided into 2 phases = Oxidative & Non-
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7. OXIDATIVE PHASE
• Step 1 = glucose 6-phosphate is oxidised by NADP
phosphate dehydrogenase (G6PD), 6-Phosphogluconolactonate is formed.
• NADPH is formed in the reaction and this is a rate limiting step.• NADPH is formed in the reaction and this is a rate limiting step.
• Step 2 = 6-phosphogluconolactonate is hydrolysed by
hydrolase to form 6- phosphogluconate
• Step 3 = the next reaction involving the synthesis of NADPH and is catalysed
by 6- phosphogluconate dehydrogenase to produce 3 keto 6
phosphogluconate which then undergoes
phosphate
OXIDATIVE PHASE
phosphate is oxidised by NADP- dependent Glucose 6-
Phosphogluconolactonate is formed.
NADPH is formed in the reaction and this is a rate limiting step.NADPH is formed in the reaction and this is a rate limiting step.
phosphogluconolactonate is hydrolysed by glucono lactone
phosphogluconate.
Step 3 = the next reaction involving the synthesis of NADPH and is catalysed
dehydrogenase to produce 3 keto 6-
which then undergoes decarboylation to give ribulose 5-
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8. NON-OXIDATIVE PHASE
• Step 4 = the ribulose-5-phosphate is then isomerised to ribose
phosphate or epimerised to xylulose
• Step 5 = Transketolase reaction
Transketolase is a thiamine pyrophosphate (TPP) dependent enzyme
It transfers 2- carbon unit from xylulose 5It transfers 2- carbon unit from xylulose 5
carbon sugar, seduhaptulose 7-phosphate and glyceraldehyde 3
phosphate.
• Step 6 = Transaldolase reaction
Transaldolase brings about the transfernof
sedohaptulose 7-phosphate to Glyceraldehyde 3
fructose 6-phosphate & 4-carbon erythrose 4
OXIDATIVE PHASE
phosphate is then isomerised to ribose-5-
phosphate or epimerised to xylulose-5- phosphate.
Transketolase is a thiamine pyrophosphate (TPP) dependent enzyme
carbon unit from xylulose 5-phosphate to form a 7-carbon unit from xylulose 5-phosphate to form a 7-
phosphate and glyceraldehyde 3-
transfernof a 3-carbon fragment from
phosphate to Glyceraldehyde 3-phosphate to give
carbon erythrose 4-phosphate
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9. • Step 7 = second transketolase reaction
• In another transketolase reaction a 2
transferred from xylulose 5-phosphate to erythrose 4
phosphate to form fructose 6
3-phosphate.3-phosphate.
• Fructose 6-phosphate & Glyceraldehyde 3
further metabolised by glycolysis & TCA cycle
Step 7 = second transketolase reaction
In another transketolase reaction a 2- carbon unit is
phosphate to erythrose 4-
phosphate to form fructose 6-phosphate & Glyceraldehyde
phosphate & Glyceraldehyde 3-phosphate are
further metabolised by glycolysis & TCA cycle
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10. SIGNIFICANCE OF HMP SHUNT
• HMP shunt is unique in generating 2 important products
• Importance of pentoses=
In HMP shunt, hexoses are converted into pentoses, the most important being ribose 5In HMP shunt, hexoses are converted into pentoses, the most important being ribose 5
phosphate
This pentose or its derivatives are useful for the synthesis of nucleic acids (DNA &
RNA)
Many nucleotides such as ATP, NAD+, FAD & CoA
SIGNIFICANCE OF HMP SHUNT
HMP shunt is unique in generating 2 important products- pentoses and NADPH
In HMP shunt, hexoses are converted into pentoses, the most important being ribose 5-In HMP shunt, hexoses are converted into pentoses, the most important being ribose 5-
This pentose or its derivatives are useful for the synthesis of nucleic acids (DNA &
Many nucleotides such as ATP, NAD+, FAD & CoA
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11. IMPORTANCE OF
• NADPH is required for the biosynthesis of fatty acids and steroids
• Also used in the synthesis of certain amino acids involving the enzyme• Also used in the synthesis of certain amino acids involving the enzyme
glutamate dehydrogenase.
• Free radical scavenging
• The free radicals (super oxide, hydrogen peroxide) are continuously
produced in all cells.
IMPORTANCE OF NADPH
NADPH is required for the biosynthesis of fatty acids and steroids
Also used in the synthesis of certain amino acids involving the enzymeAlso used in the synthesis of certain amino acids involving the enzyme
The free radicals (super oxide, hydrogen peroxide) are continuously
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12. GLUCOSE 6-
DEHYDROGENASE DEFICIENCY (G6PD)
• It is an inherited sex- linked trait
• It is more severe in RBC
• Decreased activity of G6PD impairs the synthesis of NADPH in RBC• Decreased activity of G6PD impairs the synthesis of NADPH in RBC
• This results in the accumulation of met haemoglobin & peroxides in erythrocytes leading
to hemolysis.
• The deficiency is manifested only when exposed to certain drugs or toxins,
antimalarial drug like primaquine & ingestion of fava beans (favism) & sulpha also
precipitate the hemolysis
-PHOSPHATE
DEHYDROGENASE DEFICIENCY (G6PD)
Decreased activity of G6PD impairs the synthesis of NADPH in RBCDecreased activity of G6PD impairs the synthesis of NADPH in RBC
This results in the accumulation of met haemoglobin & peroxides in erythrocytes leading
The deficiency is manifested only when exposed to certain drugs or toxins, eg. Intake of
antimalarial drug like primaquine & ingestion of fava beans (favism) & sulpha also
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13. REFERENCES
• Harper’s illustrated Biochemistry, 30E (2015)
• Biochemistry – U. Satyanarayan and U. Chakrapani 3• Biochemistry – U. Satyanarayan and U. Chakrapani 3
• Lehninger Principles of Biochemistry, fourth edition
Michael M. Cox
• Textbook of Biochemistry – DMVasudevan
REFERENCES
Harper’s illustrated Biochemistry, 30E (2015)
and U. Chakrapani 3rd editionand U. Chakrapani 3rd edition
Principles of Biochemistry, fourth edition –David L. Nelson,
DMVasudevan
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