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Pentose Phosphate Pathway (Hexose monophosphate Shunt) • Overview • Oxidative branch of Glucose • Non-oxidative: Regeneration • Modes • Red Blood cells • Glucose 6-P dehydrogenase deficency • White blood cells Overview • • • • • oxidizes Glucose located in cytoplasm produce NADPH for reductiive biosynthesis Ribose 5-P for biosynthesis of nucleotides and amino acids occurs adipose, mammary, ovary, testes, adrenal gland, bone marrow, skin, intestinal mucosa – can account for over 30% of flux of glucose • Two parts – oxidative – non-oxidative Oxidative branch • Three steps • Glucose 6-P dehydrogenase is committing step • Produces 2 NADPH, 1 CO2, 1 Ribose 5-P • Fourth step is isomerase of Ribulose to Ribose Glu 6-P + 2NADP+ H2O Æ ribose 5-P + 2NADPH + CO2 + H+ Non-oxidative Branch • Reversible • Interconverts 3,4,5,6,7 carbon sugars for synthesis of other compounds • Transketolase • Transaldolase Steps: Non-oxidative Branch Transketolase Stabilization Transketolase Transaldolase Transaldolase Summary Modes of Pentose Pathway Dependent on cytoplasmic concentration of NADP+ Liver cell NADP+ / NADPH = 0.014 while NAD+/NADH = 700 Role of Pentose Pathway Red Blood cells • detoxify oxidation products • reduce sulfhydral groups in hemoglobin, if not cross link to form Heinz bodies • Keep Fe+2 • maintain structure of RBC • Also, required lens and cornea of eye Mechanism • NADPH reduces Glutathione • Glutathione reductase catalyses reaction • Peroxide inactivation Role of Glutathione Vicia faba (fava beans) contains pamaquine Glucose 6-P dehydrogenase deficiency • • • • • • • • • sex-linked trait (11% of NA african americans, 5-10% of mediteranean and Middle eastern heritage cause oxidative stress under certain environmental conditions low levels of glutathione another genetic trait favored in malarial regions Falciparum malaria distorts surface of red blood cells targets them for destruction anit-malarial drugs cause hemolytic crisis by oxdiative stress Can survive under normal conditions White blood cells • generates oxidizing agents • NADPH oxidase • phagolysosomes and myeloperoxidase • Chronic granulomatous disease (CGD) fail to activate NADPH oxidase • Due to lack of activation of enzyme/activating system • Recurrent bacterial and fungal infections
