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Pentose Phosphate Pathway

Core outputs and why they matter

Produces:

  • NADPH

  • detoxification of ROS

  • keeps glutathione in a reduced state
  • used for fatty acid synthesis

  • ribose-5-phosphate

  • used for RNA and DNA synthesis

NADP\(^+\) vs NAD\(^+\)

  • NADP\(^+\) and NAD\(^+\) are similar except NADP\(^+\) has an extra phosphate group on the C\(2'\) position
  • they are not metabolically interchangeable

Typical cellular ratios:

  • NADH/NAD\(^+\) \(\approx 0.001\)
  • NADPH/NADP\(^+\) \(\approx 100\)

Note:

  • only glutamate dehydrogenase can use both (as noted)

Oxidative phase

Main products:

  • NADPH
  • ribulose-5-phosphate

Steps (oxidative)

  1. glucose → glucose-6-phosphate via hexokinase or glucokinase

  2. committed step:

  3. glucose-6-phosphate → 6-phosphoglucono-\(\delta\)-lactone

  4. enzyme: glucose-6-phosphate dehydrogenase
  5. NADP\(^+\) → NADPH + H\(^+\)

  6. 6-phosphoglucono-\(\delta\)-lactone → 6-phosphogluconate

  7. enzyme: gluconolactonase

  8. converts water to proton (as noted)

  9. 6-phosphogluconate → ribulose-5-phosphate

  10. enzyme: 6-phosphogluconate dehydrogenase

  11. NADP\(^+\) → NADPH
  12. releases CO\(_2\) and produces NADPH and H\(^+\) (as noted)

  13. ribulose-5-phosphate → either:

  14. ribose-5-phosphate via isomerase (keto–aldo isomerization; nucleotides)

  15. xylulose-5-phosphate via epimerase (feeds glycolysis)
  16. the direction depends on cellular need (as noted)

Non-oxidative phase

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Regulation

  • NADPH inhibits glucose-6-phosphate dehydrogenase (product inhibition)

Tissue-level notes

RBC

  • converts essentially all ribulose-5-phosphate to glycolytic intermediates

Regular cells

  • often require both NADPH and ribose-5-phosphate

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

  • X-linked recessive
  • causes hemolysis (hemolytic anemia)

  • episodic; triggers include:

  • infections

  • drugs
  • fava beans

Mechanism :

  • reduced ability to handle ROS stress because NADPH production is impaired
  • glutathione peroxidase removes ROS by oxidizing reduced glutathione
  • without sufficient NADPH, glutathione cannot be maintained in the reduced state, leading to ROS damage (including membrane damage)