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 Hexose Monophosphate 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 1)Lose a carbon 2)Reduce 2 NADP + lactonase H2OH2O

Better Picture

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

2 NADPH + H + NADP + GSH GSSG Glutathione Reductase

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

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…

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

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

G3P to Glycolysis

Non-oxidative phase

Transketolase moves 2-carbon units

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):

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.

Products in the pathway can be withdrawn at several points