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PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemis try Dr. Brad Chazotte 213 Maddox Hall [email protected] Web Site: http://www.campbell.edu/faculty /chazotte Original material only ©2000-14 B. Chazotte

PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall [email protected]

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Page 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

PENTOSE PHOSPHATE(PHOSPHOGLUCONATE)

PATHWAYStudent Edition 5/30/13 VERSION

Pharm. 304 Biochemistry

Fall 2014

Dr. Brad Chazotte 213 Maddox Hall

[email protected]

Web Site:

http://www.campbell.edu/faculty/chazotte

Original material only ©2000-14 B. Chazotte

Page 2: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

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.

Page 3: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Pentose Phosphate ReactionOverall 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

Page 4: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

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

Page 5: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Berg, Tymoczko, & Stryer 2002 Fig 20.19

PENTOSE PHOSPHATE PATHWAYOxidative Phase

Nonoxidative

Voet, Voet, & Pratt 2013 Figure 15.30

Page 6: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Berg, Tymoczko, & Stryer 2012 Table 20.3

Pentose Phosphate Pathway

Page 7: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Berg, Tymoczko, & Stryer 2012 Fig 20.19

Pentose Phosphate Pathway: Oxidative Phase

Page 8: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Voet, Voet, & Pratt 2013 Chap 15 p.508

Pentose Phosphate Pathway: Oxidative Phase Rx 1

Page 9: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Glucose 6-P Dehydrogenase Rx (#1)

Voet & Voet Biochemistry 1995 Fig. 21.24

Pentose Monophosphate Pathway

Voet, Voet & Pratt 2013 Figure 15.31

6-Phosphogluconate Dehydrogenase Rx (#3)

Page 10: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Berg, Tymoscko, & Stryer 2002 Fig 20.20b

Pentose Phosphate Pathway: Oxidative Phase Rx 2

Page 11: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Berg, Tymoscko, & Stryer 2012 Fig 20.19c

Pentose Phosphate Pathway: Oxidative Phase Rx 3

Page 12: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Linking the Pentose Phosphate and Glycolytic Pathways

[Transketolase & Transaldolase Rxs]

Page 13: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

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

Page 14: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Lehninger 2000 Fig 15.21a

Nonoxidative Reactions of the Pentose Phosphate Pathway.

Page 15: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Lehninger 2000 Fig 15.21b

Schematic: 6 Pentoses to 5 Hexoses

Page 16: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Berg, Tymoczko, & Stryer 2012 Chao. 20 p. 603

Pentose Phosphate Pathway: Transketolase Rx

Page 17: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Pentose Phosphate Pathway: Transaldolase Rx

Berg, Tymoczko, & Stryer 2012 Chao. 20 p. 603

Page 18: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Pentose Phosphate Pathway: Transketolase Rx II

Berg, Tymoczko, & Stryer 2012 Chao. 20 p. 603

Page 19: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Transketolase & Transaldolase Mechanisms

Page 20: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Berg, Tymoscko, & Stryer 2002 Fig 20.23

Carbanion Intermediates

Page 21: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Voet, Voet & Pratt 2013 Fig 15.32

Pentose Phosphate Pathway: Transketolase Mechanism

KetoseSubstrate

AldoseProduct

KetoseProduct

Aldose Substrate

Page 22: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Pentose Phosphate Pathway: Transaldolase Mechanism

KetoseSubstrate

KetoseProduct

AldoseProduct

AldoseSubstrate

Voet, Voet & Pratt 2013 Fig 15.33

Page 23: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Berg, Tymoczko, & Stryer 2012 Table 20.3

Pentose Phosphate Pathway

Page 24: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Glycolytic & Pentose Phosphate Pathways Relationships

Voet, Voet & Pratt 2013 Figure 15.34

Page 25: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

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+ + H2O ribose-5-P + 2NADPH + 2H+ +CO2

Sum of Mode 3: glucose-6-P + 12NADP+ +7 H2O 6 CO2 + 12NADPH + 12H+ +Pi

Mode 4: 3 glucose-6-P + 6 NADP+ + 5 NAD+ + 5Pi + 8 ADP 5 pyruvate + 3 CO2 + 6 NADPH = 5 NADH + 8 ATP + 8H+ +2H2O

Page 26: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

Berg, Tymoczko, & Stryer 2012 Table 20.4

Tissues with P.P. Pathway

Page 27: PENTOSE PHOSPHATE (PHOSPHOGLUCONATE) PATHWAY Student Edition 5/30/13 VERSION Pharm. 304 Biochemistry Fall 2014 Dr. Brad Chazotte 213 Maddox Hall chazotte@campbell.edu

End of Lectures