生物化学原理教学（杨荣武）Chapter24 PPP.pptVIP

Outline Overview of PPP All PPP reactions Physiological functions of PPP Regulation of PPP Pentose Phosphate Pathway Aka: Pentose shunt, Hexose monophosphate shunt and Phosphogluconate pathway It occurs in the cytosol. Two oxidative processes followed by five non-oxidative steps Operates active in the cytosol of liver and adipose cells Pentose Phosphate Pathway Cells need a constant supply of energy NADH, NADPH and ATP ATP - energy currency NADPH - reducing power Glucose -- NADH -- ATP Glucose -- NADPH -- biosynthesis (reductive) PPP Provides NADPH and ribose-5-P Glucose-6-P Dehydrogenase: Irreversible 1st step - highly regulated (inhibited by NADPH) Gluconolactonase: Uncatalyzed reaction happens too 6-Phosphogluconate Dehydrogenase: An oxidative decarboxylation Transketolase: transfer of two-carbon units Transaldolase: transfers a three-carbon unit Variations on the PPP More ribose-5-P than NADPH is needed Both ribose-5-P and NADPH are needed More NADPH than ribose-5-P is needed NADPH and ATP are needed, but ribose-5-P is not The Use of NADPH Biosynthesis fatty acids photosynthesis DNA synthesis Redox regulation of cellular processes control of cellular redox state disulfide bond formation antioxidant defense Glutathione and NADPH Glutathione Peroxidase catalyzes degradation of organic hydroperoxides by reduction, as two glutathione molecules (represented as GSH) are oxidized to a disulfide. 2 GSH + ROOH ? GSSG + ROH + H2O Glutathione Peroxidase uses the trace element selenium as functional group. The enzymes primary structure includes an analog of cysteine, selenocysteine, with Se replacing S. Regeneration of reduced glutathione requires NADPH produced in the Pentose Phosphate Pathway. Glutathione Reductase catalyzes: GSSG + NADPH + H+ →2 GSH + NADP+ Genetic deficiency of Glucose-6-P Dehydrogenase can lead to hemolytic anemia, due to inadequate [NADPH] within red blood cells. Effect of partial deficiency of Glucose-6-P Dehydrogenase is exacerbated