Unformatted text preview: Lecture 17
Overview: The pentose phosphate pathway • The pentose phosphate pathway is present in all organisms. • The role of the pentose phosphate pathway is to generate NADPH and ribose 5-phosphate in the cytoplasm. • NADPH is used later in reductive biosynthesis. • Ribose 5-phosphate is used in synthesis of RNA and DNA, as well as the nucleotide coenzymes. • Under certain cellular conditions, more NADPH than ribose 5phosphate may be needed. Under these conditions, ribose 5phosphate is converted into compounds used in other pathways, such as glyceraldehyde 3-phosphate and fructose 6-phosphate (catalyzed by transketolase and transaldolase enzymes). • The nonoxidative branch is used when more ribose 5-phosphate than NADPH is needed. Chapter 20: The Pentose Phosphate Pathway • generation of NADPH and ﬁvecarbon sugars • coordination of glucose 6phosphate metabolism in pentose phosphate pathway and glycolysis HW: 20.10, 20.15, 20.16, see last page of notes The pentose phosphate pathway The pentose phosphate pathway meets the need of all organisms to generate NADPH to use in reductive biosynthesis. Two phases of the pentose phosphate pathway Two phases: 1) the oxidative generation of NADPH Ch. 22 Ch. 26 Ch. 25 glucose 6-phosphate + 2 NADP+ + H2O -> ribose 5-phosphate + 2 NADPH + 2 H+ + CO2 2) the nonoxidative interconversion of sugars Two phases of the pentose phosphate pathway Two phases of the pentose phosphate pathway C5 + C5 C3 + C7 C4 + C5 3 C5
transketolase C3 + C7 C6 + C4 C6 + C3 transaldolase transketolase 2 C6 + C 3 Net: two hexoses and one triose from three pentoses Two phases of the pentose phosphate pathway Phase 1 The pentose phosphate pathway Step 1: dehydrogenation of glucose 6-phosphate at carbon 1 enzyme: glucose 6-phosphate dehydrogenase highly speciﬁc for NADP+; the Km for NAD+ is about 1000 times as great as that for NADP+ Phase 1 The pentose phosphate pathway Phase 1 The pentose phosphate pathway Step 2: hydrolysis of 6-phosphoglucono-!-lactone Step 3: oxidative decarboxylation enzyme: lactonase note that the ester bond in 6-phosphoglucono-!-lactone is hydrolyzed to generate an alcohol and carboxylic acid enzyme: 6=phosphogluconate dehydrogenase product is ribulose 5-phosphate Linking the pentose phosphate pathway to glycolysis Fig. 20.11, p. 572 Step 1 C5 + C5 C3 + C7 Step 2 C3 + C7 C6 + C4 Step 3 C4 + C5 C6 + C3 Tranketolase and transaldolase: stabilization of carbanionic intermediates by different mechanisms Transketolase: Excess ribose 5-phosphate formed by the pentose phosphate pathway can be completely converted into glycolytic intermediates Sum: 2 xylulose 5-phosphate + ribose 5-phosphate 2 fructose 6-phosphate + glyceraldehyde 3-phosphate 3 ribose 5-phosphate 2 fructose 6-phosphate + glyceraldehyde 3-phosphate Tranketolase and transaldolase: stabilization of carbanionic intermediates by different mechanisms Tranketolase and transaldolase: stabilization of carbanionic intermediates by different mechanisms Transaldolase: carbanion intermediates Four modes of the pentose phosphate pathway Mode 1: much more ribose 5-phosphate than NADPH is required Example: cells are dividing and need ribose 5-phosphate to synthesize DNA. 5 glucose 6-phosphate + ATP -> 6 ribose 5-phosphate + ADP + 2 H+ Mode 2: the need for ribose 5-phosphate and NADPH is equal glucose 6-phosphate + 2 NADP+ + H2O -> ribose 5-phosphate + 2 NADPH + 2 H+ + CO2 Mode 3: much more NADPH than ribose 5-phosphate is required Example: adipose tissue requires high level of NADPH for fatty acid synthesis. 6 glucose 6-phosphate + 12 NADP+ + 6 H2O -> 6 ribose 5-phosphate + 12 NADPH + 12 H+ + 6 CO2 ii) 6 ribose 5-phosphate -> 4 fructose 6-phosphate + 2 glyceraldehyde 3-phosphate iii) 4 fructose 6-phosphate + 2 glyceraldehyde 3-phosphate + H2O -> 5 glucose 6-phosphate + Pi i) Sum: glucose 6-phosphate + 12 NADP+ + 7 H2O -> 6 CO2 + 12 NADPH + 12 H+ + Pi Mode 4: both NADPH and ribose 5-phosphate are required 3 glucose 6-phosphate + 6 NADP+ + 5 NAD+ + 5 Pi + 8 ADP -> 5 pyruvate + 3 CO2 + 6 NADPH + 5 NADH + 8 ATP + 2 H2O + 8 H+ Glucose 6-phosphate dehydrogenase: role in protection against reactive oxygen species glutathione peroxidase HW problems: 1) Draw the complete mechanism for the transaldolasecatalyzed conversion of fructose 6-phosphate and erythrose 4-phosphate to glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate. 2) Draw the complete mechanism for the transketolasecatalyzed conversion of xylulose 5-phosphate and ribose 5phosphate to glyceraldehyde 3-phosphate and sedoheptulose 7-phosphate. 3) Why are these pathways needed in the organism? The answers will be given in the next class, but you should try to answer these questions yourself before class. 2 GSH + ROOH GSSG + H2O + ROH NADPH generated by glucose 6phosphate dehydrogenase maintains the appropriate levels of reduced glutathione required to combat oxidative stress ...
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This note was uploaded on 08/04/2010 for the course CHM 6620 taught by Professor Dr.christinechow during the Fall '08 term at Wayne State University.
- Fall '08