6 hmp+glucuronic


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6 hmp+glucuronic

  1. 1. Pentose Phosphate ShuntHexose Monophosphate Shunt (HMP Shunt)
  2. 2. HMP Shunt• HMP is a minor oxidation pathway for glucose• It is an alternative pathway which involves phospho–pentoses as intermediates for purposes other than energy production
  3. 3. HMP Shunt• HMP occurs in the Cytoplasm of: 1. Liver 2. Lactating mammary gland 3. Adipose tissue 4. Red blood cells 5. Adrenal cortex
  4. 4. Rate limiting Oxidation enzymeOxidative Decarboxylation
  5. 5. Hexose Monophosphate Shunt• The first step:
  6. 6. Hexose Monophosphate Shunt• Reactions of the hexose monophosphate pathways:• Enzymes numbered above are 1. Glucose 6-phosphate dehydroganase and gluconolactone hydrolyase 2. 6-phosphogluconate dehydrogenase 3. Phosphopentose isomerase 4. Phosphopentose epimerase 5. Transketolase (TPP cofactor) 6. Transaldolase 7. Transketolase (TPP cofactor)
  7. 7. 3 molecules3rd 2nd TPP 1st TPP TPP
  8. 8. 2 molecules 1 molecule
  9. 9. Regulation of HMP Shunt1. Insulin increases the activity of HMP pathway by stimulating the synthesis of dehydrogenases involved in HMP pathway2. Galactose-1-phosphate inhibits G-6-P DH
  10. 10. Metabolic Significance of HMP Shunt1) It is the only source of phosphorylated pentoses which used for the synthesis of: A. Nucleotides: ATP & GTP B. Coenzymes: FMN, FAD, NAD+ C. Certain vitamins: B2 & B12 D. Nucleic acids: DNA & RNA
  11. 11. Metabolic Significance of HMP Shunt2) It is the major source of NADPH+ which is essential for:A. Fatty acid synthesis for lipogenesis which occurs in liver, adipose tissue & lactating mammary glandB. Steroid synthesis (Adrenal cortical hormones, Sex hormones) which is active in adrenal cortex, testes, ovaries & placentaC. Act as coenzyme of glutathione reductase which keeps GSH in reduced state
  12. 12. Other NADPH+ Source• Malic enzyme (In the cytoplasm) catalyze the oxidative decarboxylation of malate to pyruvate and CO2, with the concomitant reduction of the cofactor NADP+ to NADPH Malic enz.• Malate + NADP+ pyruvate + CO2 + NADPH
  13. 13. Metabolic Significance of HMP Shunt3) NADPH is essential for keeping the reduced form of glutathione (G-SH), which is essential for keeping the red blood cell wall intact, since G-SH is essential for: A. Keeping iron of Hb in Ferrous state (Fe2+) B. Keeping globin of Hb in native structure C. Preventing accumulation of free radicals & H2O2 in RBCs So Keeping RBCs wall intact preventing hemolysis
  14. 14. Glutathione Protects us from Oxidation1 2 3 4 Protects RBCs against hemolysis
  15. 15. Oxidized Glutathione Reduced Glutathione
  16. 16. Rate limiting enzyme
  17. 17. Favism or Primaquine Sensitivity Fava beans) Aspirin)Metabolite (Like, Oxidation H2O2 Sulfa Drugs) Primaquine)H2O2 + 2 G-SH Glutathione Peroxidase 2 H2O + G-S-S-GG-S-S-G + NADPH Glutathione Reductase 2 G-SH + NADP+Glucose-6-phosphate + NADP+ Glucose-6-P DH NADPH + 6-phospho gluconolactone
  18. 18. Fava Beans
  19. 19. Child with FavismWith signs of anemia(decreased redblood cell count, jaundice, etc.)
  20. 20. Conclusion– Favism is a significant disease in society today– it plays a role similar to sickle cell anemia– It may act as a defense mechanism against malaria– The unusually high number of oxidants in the blood can kill the malaria, bacteria, Plasmodium falciparum– Interestingly, the highest incidence of this disease is found in areas where malaria is present (Mediterranean and African areas)
  21. 21. Glucuronic Acid Synthesis
  22. 22. HMP Shunt
  23. 23. Metabolic Significance of Glucuronic Acid• Glucuronic acid is used in:1. Synthesis of Proteoglycans (Glycosaminoglycans, GAGs)2. Excretion of Bilirubin and Steroid compounds (Glucuronidation)3. Detoxification of certain drugs and their metabolites by increasing their solubility (Glucuronidation)
  24. 24. Official Names of Malic Enzymes• Malate dehydrogenase (decarboxylating)• Malic enzyme• NADP-Malic enzyme• Pyruvic-Malic carboxylase• Malate + NADP+ Malic enz pyruvate + CO2 + NADPH