PPP (HMS)

Question 1

Metabolic roles of pentoses & NADPH

Answer 1

2 parts:

• 1. Oxidative part: generates NADPH by oxidation of G6P using G6PDH; NADPH used for:
     * FA syntheisis
     * Glutathione (RBC)
     * Other pathways
• 2. Non-Oxidative part: produces Ribose-5-P, which can be linked to nucleotide synthesis or glycolysis
• Depending on the tissue, Pentose Phosphates can be used for:
  
  • Nucleotide Synthesis (Liver)
  • Cholesterol synthesis (Liver)
  • Peroxide to kill bacteria (Neutrophil)

Question 2

Enzymes of oxidative part of PPP

Answer 2

• G6PDH: Glucose-6-P -> 6-Phoshogluconolactone
  
  • Generates NADPH x 1
• 6-Phoshogluconate Dehydrogenase: 6-Phosphogluconate -> Ribulose-5-P
  
  • Generates NADPH x 1 & CO2

Question 3

Enzymes of non-oxidative part of PPP

Answer 3

• Transketolase: requires Thiamine
• Transaldolase

Question 4

Role of PPP in H202 metabolism

Answer 4

• All cells except erythrocytes have an alternative source of NADPH production, e.g., NADP+-dependent Malate Dehydrogenase
  L-Malate + NADP+ -> Pyruvate + CO2 + NADPH
• Erythrocytes have no nucleus or ribosomes to produce more enzyme & must survive on enzymes they have
• Under severe oxidative stress, erythrocytes will consume all reduced glutathione. If G6PDH is mutated than NADPH cannot be produced & thus glutathione will not be reduced -> Lysis