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HMP Shunt

Glucose oxidation pathway

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HMP Shunt

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  1. Hexose Monophos-phate Shunt (HMP shunt) Dr Mukhtiar Baig

  2. Metabolic Pathways of Glucose- production and utilization Glycogenolysis Hexoseinterconversion Gluconeogenesis Production Glucose Utilization Glycolysis HMP/PPP Hexose interconversion Glycogenesis Krebs cycle

  3. Hexose Monophosphate Pathway (HMP) Alternative pathway for glucose oxidation Not meant for producing energy Site: cytosol of certain tissues e.g. liver, lactating mammary gland & adrenalgonads. Two phases Oxidative phase, glucose-6-P is oxidized with generation of 2 moles of NADPH, and one mole of pentose phosphate, with liberation of CO2. Non-oxidative phase, pentose phosphate is converted to intermediates of glycolysis.

  4. Comparison of HMP Shunt and Glycolysis

  5. The pentose pathway can be divided into two phases. Non-oxidative interconversion of sugars

  6. NADPH + H+ is formed from two separate reactions. The glucose 6-phosphate DH (G6PD) reaction is the rate limiting step and is essentially irreversible. This enzyme deficiency is one of the most common enzyme deficiency in the world.

  7. Regulatory enzyme 5 carbon atoms

  8. Importance of HMP pathway • It provides ribose5-phosphate • required for synthesis of nucleotides and nucleicacids (DNA, RNA). • Main source of NADPH, requiredfor: A)Reductases • Glutathionereductase

  9. 2. Reductases of synthesis of fattyacids • 3- HMG-CoA reductase (cholesterolsynthesis) 4- Retinalreductase • 5- Dihydrofolate (DHF)reductase • Hydroxylases • 1- Hydroxylases of caciltriol synthesis 2- Aromatic amino acid hydroxylase 3- Hydroxylases of steroidssynthesis • NADPH Oxidase:Cell membrane of phagocyticcells.

  10. Favism • Genetic deficiency of glucose-6-phosphate dehydrogenase(G6PD). • Precipitatingfactors: • Certain drugs (premaquine, aspirin or sulfonamides) Favabeans (containing divicine and otheroxidants). • Symptoms: • Asymptomatic: in betweenattacks. • Hemolytic crisis: on exposure to abovefactors. • Mechanism: G6PDdeficiency HMPinhibition Inhibition of glutathionereductase NADPH reducedglutathione failure to protect cells from oxidative damage byH2O2 Lysis ofredcells hemolyticanemia

  11. Regulation of Pentose PhosphatePathway • Allostericregulation: • NADPH is a strong inhibitor of G6PD. • Hormonalregulation: • Insulin induces synthesis of G6PD (key enzyme ofHMP).

  12. Thank you for your attention

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