Pentose Phosphate

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Pentose Phosphate

• CH339K

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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

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NADH vs NADPH

• As a general rule of thumb
• NAD/NADH is used in catabolic processes
• NADP/NADPH is used in anabolic processes

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G3P to Glycolysis
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• Oxidative Phase
• Lose a carbon
• Reduce 2 NADP

lactonase
H2O
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Better Picture
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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

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GSH
NADP
Glutathione Reductase
NADPH H
GSSG
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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 DGo from what we learned about
redox reactions
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For what its 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, Vicia
faba, is among the oldest cultivated plants -
6,000 years.
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Glucose-6-P Dehydrogenase Deficiency

• Effects 4108 people worldwide
• Most common human genetic disease
• X-linked
• 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

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Glucose-6-Phosphate Dehydrogenase Deficiency
Cappellini, M.D., and Fiorelli, G. (2008)
Glucose-6-phosphate dehydrogenase deficiency,
Lancet 371 64-74.
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Harmful Agents for G6PDD Sufferers
Antimalarials Analgesics Antibiotics Anthelmintics Miscellaneous
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
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G3P to Glycolysis
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Non-oxidative phase
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• Ribulose can be used to make ribose
• enediol intermediate

phosphopentose isomerase
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Transketolase moves 2-carbon units
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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.
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Transketolase uses a TPP cofactor
1.
2.
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Transaldolase forms a protonated Schiff base
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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.

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Multiple Functions of Pentose Phosphate Pathway
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Products in the pathway can be withdrawn at
several points