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Pentose Phosphate Pathway

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shivaveerakumar kumar

The pentose phosphate pathway, also known as the hexose monophosphate shunt, is an alternative pathway to glycolysis that helps generate reducing power in the form of NADPH and produces pentose sugars. It occurs in the cytosol in two phases - an oxidative phase that uses NADP+ to produce NADPH and CO2 from glucose-6-phosphate, and a non-oxidative phase that rearranges the pentose sugars to regenerate glucose-6-phosphate and glyceraldehyde-3-phosphate. The NADPH produced is important for biosynthesis of fatty acids and reducing glutathione for antioxidant activity, while the pentose sugars are used for nucleotide and nucleic acid synthesis. Defects

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PentosePhosphate Pathway Dr.SVK Chandrikimath
Introduction Alternative route for the metabolism of glucose Also known asHexose Monophosphate (HMP) shunt More complex pathway thanglycolysis It helpsin formation of NADPH for synthesisof fatty acids, steroids, maintaining reduced glutathione forantioxidant activity synthesis of ribose fornucleotide and nucleic acid formation
Pentose PhosphatePathway Likeglycolysis it occurs incytosol Oxidation is achieved by dehydrogenation using NADP+,not NAD+ Its carried out in 2step: 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 phosphateand 1 molecule of the glyceraldehyde-3phosphate
Oxidativephase Dehydrogenation of glucose-6- phosphate to 6- phosphogluconate catalyzedby glucose 6-phosphate dehydrogenase Followed by hydrolysisof 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 hydrogenacceptor
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 nucleicacid synthesis Ribulose-5-phosphate 3-epimerase: alters the configuration about carbon giving xylulose 5- phosphate
Non-oxidativePhase Xylulose-5-phosphate (5c) and Ribose-5- phosphate (5c) reacts to giveGlyceraldehyde- 3-phosphate (3c) and Sedoheptulose-7- phosphate (7c) by the enzymeTransketolase Glyceraldehyde-3-phosphate (3c) and Sedoheptulose-7-phosphate (7c) is acted by Transaldolase to give Fructose-6-phosphate and Erythrose-4-phosphate
Non-oxidativePhase Erythrose-4-phosphate and Xylulose-5-phosphate reacts in the presence of enzyme Transketolase togive Fructose-6-phosphate and Glyceraldehyde-3- phosphate Mg 2+and thiamin diphosphate (vitamin B1)ascoenzyme 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 itproceeds to glycolysis.
Pentose Phosphate Pathway
Importance of NADPH Bio-synthesis of Fattyacid Certain amino acid involving the enzyme glutamatedehydrogenase Antioxidant reaction Glutathionemediated reaction of H2O2 Detoxification of drugs cytochromeP450 Phagocytosis Integrity of RBCmembrane
Importance of PentoseSugar Ribose-5 phosphate useful for the synthesis of nucleic acid (RNAand DNA)and nucleotide Skeletal muscles capable of synthesizing pentoses
CLINICAL SIGNIFICANCE Genetic defects of glucose-6-phosphate dehydrogenase impairment of the generation of NADPH-X chromosome Mediterranean andAfro-Caribbeanorigin red cell hemolysis (hemolyticanemia) subjected to oxidativestress Infection Drugssuchasthe antimalarial primaquine, and sulfonamides Favabeans - favism

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Pentose Phosphate Pathway

  • 2. Introduction Alternative route for the metabolism of glucose Also known asHexose Monophosphate (HMP) shunt More complex pathway thanglycolysis It helpsin formation of NADPH for synthesisof fatty acids, steroids, maintaining reduced glutathione forantioxidant activity synthesis of ribose fornucleotide and nucleic acid formation
  • 3. Pentose PhosphatePathway Likeglycolysis it occurs incytosol Oxidation is achieved by dehydrogenation using NADP+,not NAD+ Its carried out in 2step: 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 phosphateand 1 molecule of the glyceraldehyde-3phosphate
  • 4. Oxidativephase Dehydrogenation of glucose-6- phosphate to 6- phosphogluconate catalyzedby glucose 6-phosphate dehydrogenase Followed by hydrolysisof 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 hydrogenacceptor
  • 5. 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 nucleicacid synthesis Ribulose-5-phosphate 3-epimerase: alters the configuration about carbon giving xylulose 5- phosphate
  • 6. Non-oxidativePhase Xylulose-5-phosphate (5c) and Ribose-5- phosphate (5c) reacts to giveGlyceraldehyde- 3-phosphate (3c) and Sedoheptulose-7- phosphate (7c) by the enzymeTransketolase Glyceraldehyde-3-phosphate (3c) and Sedoheptulose-7-phosphate (7c) is acted by Transaldolase to give Fructose-6-phosphate and Erythrose-4-phosphate
  • 7. Non-oxidativePhase Erythrose-4-phosphate and Xylulose-5-phosphate reacts in the presence of enzyme Transketolase togive Fructose-6-phosphate and Glyceraldehyde-3- phosphate Mg 2+and thiamin diphosphate (vitamin B1)ascoenzyme 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 itproceeds to glycolysis.
  • 9. Importance of NADPH Bio-synthesis of Fattyacid Certain amino acid involving the enzyme glutamatedehydrogenase Antioxidant reaction Glutathionemediated reaction of H2O2 Detoxification of drugs cytochromeP450 Phagocytosis Integrity of RBCmembrane
  • 10. Importance of PentoseSugar Ribose-5 phosphate useful for the synthesis of nucleic acid (RNAand DNA)and nucleotide Skeletal muscles capable of synthesizing pentoses
  • 11. CLINICAL SIGNIFICANCE Genetic defects of glucose-6-phosphate dehydrogenase impairment of the generation of NADPH-X chromosome Mediterranean andAfro-Caribbeanorigin red cell hemolysis (hemolyticanemia) subjected to oxidativestress Infection Drugssuchasthe antimalarial primaquine, and sulfonamides Favabeans - favism