Pentose phosphate pathway

Question 1

what does the PPP do

Answer 1

provides NADH from abundant G6P in cytoplasm. also makes substrates for glycolysis/gluconeogenisis/nucleotide metabolism

NADH: typically catabolic for energy production (ETC and oxidative phosphorylation) NADH/NAD= .0014

NADPH: anabolic for reductive reactions and synthesis of fats to combat reactive oxygen species NADPH/NADP= 70

Question 2

2 stages of PPP

Answer 2

Oxidative: IRREVERSIBle
G6P + NADP -> CO2, 2 NADPH, ribulose 5 P (via glucose 6 phosphate dehydrogenase) rate limiting step and NADPH inhibits it

Nonoxidative, REVERSIBLE

Ribulose 5 P ribose 5 P, glyceraldehyde 3 P, fructose 6 P (via transketolose, transaldolase/pppisomerase along with a B1 cofactor)

Question 3

Where does PPP occur

Answer 3

liver, mammary glands, adipose tissue

Need NADPH for fatty acid synthesis, adrenal cortex uses NADPH for microsomal cytochrome P450 monooxogynase system

Question 4

NADPH role in combating reactive oxygen species

Answer 4

NADPH uses reduced glutathione (GSH)
GSH is an antioxidant that reduces protein disulfides, H2O2 and organic peroxides via glutathione peroxidase in eye and RBCs

GSSG + NADPH -> 2 GSH + NADP+ (using glutathione reductase)

Question 5

Oxidative stage

Answer 5

G6P-> CO2, 2 NADPH, Ribulose 5P

G6P-> 6Pgluconolactone + NADPH (via G6P dehydrogenase)
commited step, rate limiting step, regulated by substrate availability (NADP), regulated by product competitive inhibition (NADPH)

Question 6

Non oxidative PPP stage

Answer 6

Ribulose 5 P -> Ribose 5 P, glyceraldehyde 3P, Fructose 6 P

via Transketolose (requires thiamine pyrophosphate (B1)
and Translaldolase makes a schiff base, no cofactor needed

Question 7

Function of PPP

Answer 7

1. NADPH for synthesis or GSSG reduction:
   - uses oxidative branch to reduce NADP-> NADPH
   - use nonoxidative Ribulose 5P-> glycolitic intermediate so the carbons arent wasted
   - control is automatic if NADP+ accumulates, 6 phosphogluconate dehydrogenase will act on it -> NADPH
2. Ribose 5 P to make nucleotides
   - uses nonoxidative branch F6P-> ribose 5 P
   - doesnt need oxidative branch
   - control is automatic

Question 8

Medical implication

Answer 8

glucose 6 phosphate dehydrogenase deficiency is the most common enzyme abnormaility affecting humans

X linked
causes hemolytic anemia in RBCs

poor ROS defense, cant make GSH from GSSG