Uses of NADPH in various systems of human bodies. Its role in G6PD deficiency

1. NADPH & Its Uses
Prepared by: Anish Dhakal
anishdhakal718@gmail.com

2. Objectives
• NADPH
• Rationale of two distinct reducing
equivalents NADH & NADPH
• Uses of NADPH
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3. What is NADPH?
• Reduced form of Nicotinamide
adenine dinucleotide phosphate
• Necessity of Vital Anabolic Processes
• Major source is Pentose Phosphate
Pathway
• Deficiency unequivocally subjects cell
to oxidative stress
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4. NADH Vs NADPH ???
• Two distinct redox cofactors prevent
futile metabolic cycles (synthesis &
degradation of molecule of interest)
• Phosphate group enables reducing
agents to recognize two separate set of
enzymes
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5. How are they regulated ???
• Anabolic and Catabolic Processes are
controlled independently
• NAD/NADH ratio is high to supply
enough oxidants for catabolic process
• NADP/NADPH ratio is low to supply
enough NADPH to power anabolic
process
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6. Uses of NADPH
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7. Reductive Biosynthesis
• Electron donor for synthesis of Fatty
acids, sterols, hormones and bile salts
• Unlike its catabolic counterpart which
transfers oxygen, its electrons are used
exclusively for reductive biosynthesis
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8. Cytochrome P450
Monooxygenase System
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9. Cytochrome P450
Monooxygenase System
Mitochondral
•Hydroxylate Steroid hormones & Vitamin D
Microsomal
• Detoxification of Xenobiotic for two sole
purposes
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10. Phagocytosis
by WBCs
• Oxygen dependent
• Include MPO system
• Involves the enzyme
NADPH oxidase
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11. Synthesis of Nitric Oxide
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12. Prevention of Methemoglobin
• Methemoglobin constitutes Ferric form
of Fe unable to transport oxygen
• NADPH mediated reaction with
enzyme Methemoglobin reductase
reduces it to normal hemoglobin
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13. Reduction of Hydrogen Peroxide
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14. G6PD Deficiency
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15. G6PD Deficiency
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16. G6PD Deficiency: Occurs in
all cells
Why RBC to suffer???
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17. RBC are just more vulnerable
• Only mechanism for NADPH
production in RBCs is Pentose
Phosphate Pathway
• No nucleus or ribosomes to renew the
supply of enzymes
• Other cells have enzymes like NADP
linked malate dehydrogenase for
NADPH synthesis
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