PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu Web Site: http://www.campbell.edu/faculty/chazotte Original material only ©2000-14 B. Chazotte Pharm. 304 Biochemistry Fall 2014 Goals • Learn the Pentose Phosphate Pathway and its oxidative and non-oxidative phases. • Learn what the Pentose phosphate pathway produces and how it can react to various metabolic demands (pathway modes of operation) • Be familiar with the pathways that require pathway products. • Understand the role of the transketolase and transaldolase reactions. Pentose Phosphate Reaction Overall 3 Glucose-6-P + 6 NADP+ + 3 H2O 6 NADPH + 6 H+ + 3CO2 + 2F-6-P + GAP Stage 1 3G-6-P + 6 NADP+ + 3 H2O 6 NADPH + 6 H+ + 3CO2 Stage 2 3Ru5P R5P + 2 Xu5P Stage 3 R5P + 2Xu5P 2F6P + GAP Voet & Voet 1995 Chap 21 p. 617-9 Pathways That Require NADPH Two key functions: 1. It provides all organisms with a source of NADPH to use on reductive biosynthesis 2. Generates pentose sugars, particularly ribose Berg, Tymoczko, & Stryer 2012 Table 20.4 PENTOSE PHOSPHATE PATHWAY Oxidative Phase Nonoxidative Berg, Tymoczko, & Stryer 2002 Fig 20.19 Voet, Voet, & Pratt 2013 Figure 15.30 Pentose Phosphate Pathway Berg, Tymoczko, & Stryer 2012 Table 20.3 Pentose Phosphate Pathway: Oxidative Phase Berg, Tymoczko, & Stryer 2012 Fig 20.19 Pentose Phosphate Pathway: Oxidative Phase Rx 1 Voet, Voet, & Pratt 2013 Chap 15 p.508 Glucose 6-P Dehydrogenase Rx (#1) 6-Phosphogluconate Dehydrogenase Rx (#3) Voet & Voet Biochemistry 1995 Fig. 21.24 Pentose Monophosphate Pathway Voet, Voet & Pratt 2013 Figure 15.31 Pentose Phosphate Pathway: Oxidative Phase Rx 2 Berg, Tymoscko, & Stryer 2002 Fig 20.20b Pentose Phosphate Pathway: Oxidative Phase Rx 3 Berg, Tymoscko, & Stryer 2012 Fig 20.19c Linking the Pentose Phosphate and Glycolytic Pathways [Transketolase & Transaldolase Rxs] Linking the Pentose Pathway and Glycolysis Transketolase C5 + C5 C3 + C7 Transaldolase C3 + C7 C6 + C4 Transketolase C4 + C5 C6 + C3 Net Reaction 3 C5 2 C6 + C3 Berg, Tymoczko, & Stryer 2012 Chap 20 Nonoxidative Reactions of the Pentose Phosphate Pathway. Lehninger 2000 Fig 15.21a Schematic: 6 Pentoses to 5 Hexoses Lehninger 2000 Fig 15.21b Pentose Phosphate Pathway: Transketolase Rx Berg, Tymoczko, & Stryer 2012 Chao. 20 p. 603 Pentose Phosphate Pathway: Transaldolase Rx Berg, Tymoczko, & Stryer 2012 Chao. 20 p. 603 Pentose Phosphate Pathway: Transketolase Rx II Berg, Tymoczko, & Stryer 2012 Chao. 20 p. 603 Transketolase & Transaldolase Mechanisms Carbanion Intermediates Berg, Tymoscko, & Stryer 2002 Fig 20.23 Pentose Phosphate Pathway: Transketolase Mechanism Ketose Substrate Ketose Product Aldose Product Aldose Substrate Voet, Voet & Pratt 2013 Fig 15.32 Pentose Phosphate Pathway: Transaldolase Mechanism Aldose Product Ketose Substrate Ketose Product Aldose Substrate Voet, Voet & Pratt 2013 Fig 15.33 Pentose Phosphate Pathway Berg, Tymoczko, & Stryer 2012 Table 20.3 Glycolytic & Pentose Phosphate Pathways Relationships Voet, Voet & Pratt 2013 Figure 15.34 Four Modes of the Pentose Phosphate Pathway Mode 1: Mode 2: Sum of Mode 3: Mode 4: 5 glucose-6-P + ATP 6 ribose-5-P + ADP + H+ glucose-6-P + 2NADP+ + H2O ribose-5-P + 2NADPH + 2H+ +CO2 glucose-6-P + 12NADP+ +7 H2O 6 CO2 + 12NADPH + 12H+ +Pi 3 glucose-6-P + 6 NADP+ + 5 NAD+ + 5Pi + 8 ADP 5 pyruvate + 3 CO2 + 6 NADPH = 5 NADH + 8 ATP + 8H+ +2H2O Berg, Tymoscko, & Stryer 2002 Fig 20.24 Tissues with P.P. Pathway Berg, Tymoczko, & Stryer 2012 Table 20.4 End of Lectures