Pentose Phosphate Pathway Central Washington 磷酸戊糖途径华盛顿市中心.pptVIP

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Pentose Phosphate Pathway Central Washington 磷酸戊糖途径华盛顿市中心.ppt

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Pentose Phosphate Pathway Central Washington 磷酸戊糖途径华盛顿市中心

Pentose Phosphate Pathway Generation of NADPH and Pentoses Overview Function NADPH production Reducing power carrier Synthetic pathways Role as cellular antioxidants Ribose synthesis Nucleic acids and nucleotides Characteristics:Tissue Distribution Demand for NADPH Biosynthetic pathways FA synthesis (liver, adipose, mammary) Cholesterol synthesis (liver) Steroid hormone synthesis (adrenal, ovaries, testes) Detoxification (Cytochrome P-450 System) – liver Reduced glutathione as an antioxidant (RBC) Generation of superoxide (neutrophils) Characteristics:Oxidative and Non-oxidative Phases Oxidative phases Reactions producing NADPH Irreversible Non-oxidative phases Produces ribose-5-P Reversible reactions feed to glycolysis NADPH producing reactions Glucose-6-P dehydrogenase 6-P-gluconate dehydrogenase The Pentose Phosphate Pathway:Non-oxidative phases Regulation Glucose-6-P dehydrogenase First step Rate limiting Allosteric Regulation Feedback inhibited by NADPH Inducible enzyme Induced by insulin Role of NADPH in the RBC Production of superoxide Hb-Fe2+-O2 - Hb-Fe3+ + O2-. Spontaneous rxn, 1% per hour O2-. + 2H2O - 2H2O2 Both O2-. H2O2 can produce reactive free radical species, damage cell membranes, and cause hemolysis Detoxification of Superoxide Anion and Hydrogen Peroxide Antioxidant enzymes Superoxide dismutase Glutathione peroxidase Glutathione reductase Case Study 21 yo male medical student with malaria Treated with primaquine Four days later: Black colored urine Low RBC count Elevated reticulocyte count RBC with Heinz bodies Low hemoglobin Elevated serum bilirubin Pt recovered in a few days G6PDH Deficiency and Hemolytic Anemia Most common genetic enzymopathy 400 hundred variants of G6PDH deficiency Mediterranean, Asian, African descent 400 million people affected worldwide 50% of Kurdish men 10-14% of African-American men with G6PD deficiency Worldwide distribution of G6PD deficiency: 1995 G6PD Deficiency Distribution of G6PD deficiency coincides preval