1. Pentose Phosphate CH339K

2. 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 Hexose Monophosphate Shunt

3. NADH vs NADPH As a general rule of thumb: NAD + /NADH is used in catabolic processes NADP + /NADPH is used in anabolic processes

4. G3P to Glycolysis

5. Oxidative Phase 1)Lose a carbon 2)Reduce 2 NADP + lactonase H2OH2O

9. Better Picture

10. Glutathione -SH containing tripeptide Glu-Cys-Gly Amino of Cysteine linked to  -carboxyl of glutamate Commonly used for reducing agent in cells Oxidizes to for disulfide-linked GSSG Rereduced to GSH using NADPH

11. 2 NADPH + H + NADP + GSH GSSG Glutathione Reductase

12. Making Glutathione For the Reaction to form GSH: GSSG + 2e - + 2H + ⇄ 2GSH-0.23 V NADPH + H + ⇄ NADP + + 2e - + 2 H + +0.32 V GSSG + NADPH + H + ⇄ 2GSH + NADP + +0.09 V We can figure out  G o from what we learned about redox reactions

14. 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, Vicia faba, is among the oldest cultivated plants - ~6,000 years. For what it’s worth…

15. Glucose-6-P Dehydrogenase Deficiency Effects ~ 4*10 8 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

16. Harmful Agents for G6PDD Sufferers AntimalarialsAnalgesicsAntibioticsAnthelminticsMiscellaneous Primaquine Pamaquine Chloroquine Aspirin Bufferin Anacin Excedrin Empirin APC Tablets Darvon Compound Coricidin Sulfanilamide Sulfapyridine Sulfadimidine Sulfacetamide Glucosulfone sodium Nitrofurantoin Furazolidone Nitrofurazone Dapsone Sulfoxone Sulfisoxazole B-Naphthol Stibophen Niridazole Probenecid Thiazide Diuretics Phenothiazine Chloramphenicol Orinase Dimercaprol Methylene blue Naphthalene (moth balls) Vitamin K Fava beans

17. G3P to Glycolysis

18. Non-oxidative phase

23. Transketolase moves 2-carbon units

24. 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.

31. 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.

33. Products in the pathway can be withdrawn at several points