1. PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu Web Site: http://www.campbell.edu/faculty/chazotte http://www.campbell.edu/faculty/chazotte Original material only ©2000-14 B. Chazotte

2. 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.

3. Pentose Phosphate Reaction Overall 3 Glucose-6-P + 6 NADP + + 3 H 2 O  6 NADPH + 6 H + + 3CO 2 + 2F-6-P + GAP Stage 1 3G-6-P + 6 NADP + + 3 H 2 O  6 NADPH + 6 H + + 3CO 2 Stage 2 3Ru5P  R5P + 2 Xu5P Stage 3R5P + 2Xu5P  2F6P + GAP Voet & Voet 1995 Chap 21 p. 617-9

4. Berg, Tymoczko, & Stryer 2012 Table 20.4 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

5. Berg, Tymoczko, & Stryer 2002 Fig 20.19 PENTOSE PHOSPHATE PATHWAY Oxidative Phase Nonoxidative Voet, Voet, & Pratt 2013 Figure 15.30

6. Berg, Tymoczko, & Stryer 2012 Table 20.3 Pentose Phosphate Pathway

7. Berg, Tymoczko, & Stryer 2012 Fig 20.19 Pentose Phosphate Pathway: Oxidative Phase

8. Voet, Voet, & Pratt 2013 Chap 15 p.508 Pentose Phosphate Pathway: Oxidative Phase Rx 1

9. Glucose 6-P Dehydrogenase R x (#1) Voet & Voet Biochemistry 1995 Fig. 21.24 Pentose Monophosphate Pathway Voet, Voet & Pratt 2013 Figure 15.31 6-Phosphogluconate Dehydrogenase R x (#3)

10. Berg, Tymoscko, & Stryer 2002 Fig 20.20b Pentose Phosphate Pathway: Oxidative Phase R x 2

11. Berg, Tymoscko, & Stryer 2012 Fig 20.19c Pentose Phosphate Pathway: Oxidative Phase R x 3

12. Linking the Pentose Phosphate and Glycolytic Pathways [Transketolase & Transaldolase R x s]

13. Linking the Pentose Pathway and Glycolysis Transketolase C 5 + C 5 C 3 + C 7 Transaldolase C 3 + C 7 C 6 + C 4 Transketolase C 4 + C 5 C 6 + C 3 Net Reaction 3 C 5 2 C 6 + C 3 Berg, Tymoczko, & Stryer 2012 Chap 20

14. Lehninger 2000 Fig 15.21a Nonoxidative Reactions of the Pentose Phosphate Pathway.

15. Lehninger 2000 Fig 15.21b Schematic: 6 Pentoses to 5 Hexoses

16. Berg, Tymoczko, & Stryer 2012 Chao. 20 p. 603 Pentose Phosphate Pathway: Transketolase Rx

17. Pentose Phosphate Pathway: Transaldolase Rx Berg, Tymoczko, & Stryer 2012 Chao. 20 p. 603

18. Pentose Phosphate Pathway: Transketolase Rx II Berg, Tymoczko, & Stryer 2012 Chao. 20 p. 603

19. Transketolase & Transaldolase Mechanisms

20. Berg, Tymoscko, & Stryer 2002 Fig 20.23 Carbanion Intermediates

21. Voet, Voet & Pratt 2013 Fig 15.32 Pentose Phosphate Pathway: Transketolase Mechanism Ketose Substrate Aldose Product Ketose Product Aldose Substrate

22. Pentose Phosphate Pathway: Transaldolase Mechanism Ketose Substrate Ketose Product Aldose Product Aldose Substrate Voet, Voet & Pratt 2013 Fig 15.33

23. Berg, Tymoczko, & Stryer 2012 Table 20.3 Pentose Phosphate Pathway

24. Glycolytic & Pentose Phosphate Pathways Relationships Voet, Voet & Pratt 2013 Figure 15.34

25. Berg, Tymoscko, & Stryer 2002 Fig 20.24 Four Modes of the Pentose Phosphate Pathway Mode 1: 5 glucose-6-P + ATP 6 ribose-5-P + ADP + H + Mode 2: glucose-6-P + 2NADP + + H 2 O ribose-5-P + 2NADPH + 2H + +CO 2 Sum of Mode 3: glucose-6-P + 12NADP + +7 H 2 O 6 CO 2 + 12NADPH + 12H + +P i Mode 4: 3 glucose-6-P + 6 NADP+ + 5 NAD+ + 5Pi + 8 ADP 5 pyruvate + 3 CO 2 + 6 NADPH = 5 NADH + 8 ATP + 8H+ +2H2O

26. Berg, Tymoczko, & Stryer 2012 Table 20.4 Tissues with P.P. Pathway

27. End of Lectures