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Pentose Phosphate. CH339K. Pentose Phosphate. An example of a pathway that can be both: Anabolic Generates ribose-5-phosphate for nucleotide synthesis Metabolizes dietary pentoses into glycolytic / gluconeogenic intermediates. Catabolic Generates reducing power (NADPH )
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Pentose Phosphate CH339K
Pentose Phosphate An example of a pathway that can be both: • Anabolic • Generates ribose-5-phosphate for nucleotide synthesis • Metabolizes dietary pentoses into glycolytic/gluconeogenic intermediates. • Catabolic • Generates reducing power (NADPH) • Can completely oxidize glucose • Can carry on into glycolysis Aka HexoseMonophosphate Shunt
NADH vs NADPH • As a general rule of thumb: • NAD+/NADH is used in catabolic processes • NADP+/NADPH is used in anabolic processes
G3P to Glycolysis
Oxidative Phase Lose a carbon Reduce 2 NADP+ lactonase H2O
Glutathione -SH containing tripeptide Glu-Cys-Gly Amino of Cysteine linked to g-carboxyl of glutamate Commonly used for reducing agent in cells Oxidizes to for disulfide-linked GSSG Rereduced to GSH using NADPH
2 GSH NADP+ Glutathione Reductase NADPH + H+ GSSG
Making Glutathione • For the Reaction to form GSH: We can figure out DGo from what we learned about redox reactions
For what it’s worth… Divicine is found in fava beans and some other legumes Favas (broad beans) are common foodstuffs in the old world. Largest production in Europe and China. The parent plant, Viciafaba, is among the oldest cultivated plants - ~6,000 years.
Glucose-6-P Dehydrogenase Deficiency • Effects ~ 4*108 people worldwide • Most common human genetic disease • Lack of G-6PD means lack of NADPH • Lack of NADPH means lack of GSH • Lack of GSH means excess of peroxides • RBC membranes particularly susceptible to peroxides • Hemolytic Anemia
G3P to Glycolysis
Transaldolase moves 3-carbon units Lack of transketolase can cause hepatosplenomegaly and liver cirrhosis in childhood. Verhoeven, N. M. et al (2001) Transaldolase Deficiency: Liver Cirrhosis Associated with a New Inborn Error in the Pentose Phosphate Pathway , Amer. J. Hum. Gen. 68(5): 1086-1092.
Control • Conversion of glucose-6-Pi to the lactone is essentially irreversible. • The enzyme, glucose-6-phosphate dehydrogenase, controls the rate of the pathway. • NADPH competes with NADP for binding in he active site; • ATP competes with glucose-6-phosphate. • At high [NADPH] and/or high [ATP], entrance into the pathway is restricted.
