pentose phosphate pathway - western oregon universitywou.edu › ~guralnl › 451pentose phosphate...
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Pentose Phosphate Pathway(Hexose monophosphate Shunt)
• Overview• Oxidative branch of
Glucose• Non-oxidative:
Regeneration• Modes• Red Blood cells• Glucose 6-P
dehydrogenasedeficency
• White blood cells
Overview • oxidizes Glucose • located in cytoplasm • produce NADPH for
reductiive biosynthesis• Ribose 5-P for biosynthesis
of nucleotides and amino acids
• occurs adipose, mammary, ovary, testes, adrenal gland, bone marrow, skin, intestinal mucosa– can account for over 30% of
flux of glucose • Two parts
– oxidative – non-oxidative
Oxidative branch
• Three steps • Glucose 6-P
dehydrogenase is committing step
• Produces 2 NADPH, 1 CO2, 1 Ribose 5-P
• Fourth step is isomerase of Ribulose to Ribose
Glu 6-P + 2NADP+ H2O ribose 5-P + 2NADPH + CO2 + H+
Non-oxidative Branch
• Reversible • Interconverts
3,4,5,6,7 carbon sugars for synthesis of other compounds
• Transketolase• Transaldolase
Steps: Non-oxidative Branch
Transketolase
Stabilization
Transketolase
Transaldolase
Transaldolase
Summary
Modes of Pentose PathwayDependent on cytoplasmic concentration of NADP+
Liver cell NADP+ / NADPH = 0.014 while NAD+/NADH = 700
Role of Pentose Pathway
Red Blood cells
• detoxify oxidation products
• reduce sulfhydral groups in hemoglobin, if not cross link to form Heinz bodies
• Keep Fe+2
• maintain structure of RBC • Also, required lens and
cornea of eye
Mechanism
• NADPH reduces Glutathione
• Glutathione reductase catalyses reaction
• Peroxide inactivation
Role of Glutathione
Vicia faba (fava beans) containspamaquine
Glucose 6-P dehydrogenasedeficiency
• sex-linked trait (11% of NA africanamericans, 5-10% of mediteraneanand Middle eastern heritage
• cause oxidative stress under certain environmental conditions
• low levels of glutathione • another genetic trait favored in
malarial regions • Falciparum malaria • distorts surface of red blood cells • targets them for destruction • anit-malarial drugs cause hemolytic
crisis by oxdiative stress • Can survive under normal
conditions
White blood cells • generates oxidizing
agents • NADPH oxidase• phagolysosomes and
myeloperoxidase• Chronic granulomatous
disease (CGD) fail to activate NADPH oxidase
• Due to lack of activation of enzyme/activating system
• Recurrent bacterial and fungal infections