Key Functions & Purpose

  1. Produce NADPH: Used for:
    • Reductive Biosynthesis: Fatty acid synthesis, cholesterol/steroid synthesis, part of Respiratory burst
    • Antioxidant Defense: Essential for regenerating reduced glutathione, which detoxifies reactive oxygen species (e.g., H₂O₂). This is particularly crucial in RBCs.
  2. Produce Ribose-5-Phosphate (R5P): A precursor for nucleotide (DNA, RNA) and coenzyme (NAD+, FAD, CoA) synthesis.

Pathway Phases

  1. Oxidative Phase (Irreversible)

    • Purpose: Generates 2 NADPH from one molecule of Glucose-6-Phosphate (G6P).
    • Rate-Limiting Enzyme: Glucose-6-Phosphate Dehydrogenase (G6PD).
      • Converts G6P to 6-phosphogluconolactone.
      • Induced by: NADP+, Insulin.
      • Inhibited by: NADPH (product inhibition).
    • Location: Tissues with high demand for NADPH (e.g., liver, adrenal cortex, lactating mammary glands, RBCs).
  2. Non-Oxidative Phase (Reversible)

    • Purpose: Interconverts ribulose-5-phosphate (product of oxidative phase) into ribose-5-phosphate (for nucleotide synthesis) or glycolytic intermediates (Fructose-6-P, Glyceraldehyde-3-P). This allows the pathway to be flexible based on the cell’s metabolic needs.
    • Key Enzymes:
      • Transketolase: Requires Thiamine (Vitamin B1) as a cofactor. Transfers 2-carbon units.
      • Transaldolase: Transfers 3-carbon units.
  • Occurs in cytoplasm of liver cells