Pentose Phosphate Pathway

Def

alternative pathway of glucose metabolism

PPP loco

cytosol of all cells

Two main functions

• produce NADPH (for biosynthesis + antioxidant defense)

• Produce ribose 5- phosphate (nucleotide synthesis)

Tissues with high PPP activity

liver, adipose tissue, adrenal cortex, mammary glands

Phase of PPP

• Oxidative phase: step 1-3 (irreversible) → produce NADPH

• Nonoxidative phase: step 4-8 ( reversible) → rearranged sugars

PPP: Step 1

Glucose-6-phosphate → 6-phosphogluconolactone by glucose-6-phosphate DH

• Key point: rate limiting/committed step

• inhibited by NADPH (product inhibition)

• activated when NADP+ increased

PPP: Step 2

6-phosphogluconolactone → 6-phosphogluconate by gluconolactonase

PPP: Step 3

6-phosphogluconate → ribose-5-p by 6-phosphogluconate by 6-phosphogluconate DH

• Key point: oxidation + decarboxylation

Net oxidative phase

3 G6P + 6 NADP+ → 2 ribulose-5-P + 3 co2 + 6 NADPH + 6 H+

PPP: Step 4

ribulose-5-P → ribose-5-P by phosphopentose isomerase

• Mech ketose → aldose (enediol interm) → rearranged carbonyl

PPP: Step 5

Ribulose-5-P → xylulose-5-P by phosphopentose epimerase

• Mech: epimerization at c3 → base removes H → flips sterochem

PPP: Step 6

Xyluluose-5-P + ribose-5-P → G3P + sedheptulose-7-p by Transketolase

• cofactor needed: Thiamine pyrophosphate (TTP) (Vit B1)

• froms carbanion inter

• Func: transfers 2-carbon fragment

PPP: Step 7

G3P + sedoheptulose-7-P → fructose-6-P +erythrose-4-P by transaldolase

Transaldolase

• Mech: schiff base (lysine)

• forms imine inter

• Func: transfers 3 carbon units

PPP: Step 8

xylulose-5-P + erythrose-4-P → fructose-6-P + G3P by transketolase

Net nonoxidative Phase

2 xylulose-5-P + ribose-5-P → glycolysis intermediates ( 2 F6P + G3P)

Overall net PPP

3 G6P + 6 NADP+ → 2 F6P + G3P + 3 co2 + 6 NADPH + 6 H+

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