Medicine & USMLE

Pentose Phosphate Pathway - Non-Oxidative Phase

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Metabolism
  1. Citric Acid Cycle (TCA, Krebs)
  2. Glycolysis - Investment Phase
  3. Glycolysis - Payoff Phase
  4. Pentose Phosphate Pathway - Oxidative Phase
  5. Pentose Phosphate Pathway - Non-Oxidative Phase
  6. Glycogenesis
  7. Glycogenolysis
  8. Gluconeogenesis
  9. Electron Transport Chain (ETC)

Summary

The pentose phosphate pathway is composed of two parts: an oxidative phase and a non-oxidative phase.

The non-oxidative phase consists of a bunch reversible, carbon-carbon rearrangements. Its primary purpose is to generate pentose phosphates, chiefly ribose-5-phosphate, which is important for nucleotide synthesis. It also provides a way for us to shunt pentose phosphate pathway molecules back into glycolysis—and vice versa.

Since the pentose phosphate pathway interconnects with glycolysis, it should make sense that this pathway takes place in the cytosol.

Key Points

  • Pentose Phosphate Pathway (PPP) non-oxidative phase
    • Etymology
      • also called the hexose monophosphate shunt
        • Glucose-6-phosphate (starting substrate) is a hexose ring with 1 phosphate group that is ‘shunted’ from glycolysis to enter the PPP
    • Summary
      • Pentose Phosphate Pathway (PPP) is a metabolic pathway that generates NADPH and precursor molecules for biosynthesis
      • PPP occurs in the cytoplasm
        • Interconnects with glycolysis
          • glycolysis also occurs in the cytoplasm
          • PPP starting substrate, glucose-6-phosphate, is produced by the first step of glycolysis (link)
            • Can be produced in other ways too
      • Two phases
        • Oxidative phase: generates NADPH (link)
        • Nonoxidative phase: generates precursors for biosynthesis
          • Precursors for nucleotide synthesis
          • Reactions are carbon-carbon rearrangements
            • All reversible reactions
          • Some intermediates can enter other metabolic pathways (such as glycolysis)
    • reaction steps (non-oxidative phase)
      • Ribulose-5-phosphate → [ribulose-5-phosphate Isomerase] ribose-5-phosphate
        • 1st of two enzymes that metabolizes ribulose-5-phosphate
        • Ribose-5-phosphate is used in nucleotide synthesis (DNA and RNA)
      • Ribulose-5-phosphate → [ribulose-5-phosphate 3-Epimerase] Xylulose-5-phosphate
        • 2nd of two enzymes that metabolizes ribulose-5-phosphate
      • Ribose-5-phosphate + Xylulose-5-phosphate → [Transketolase] glyceraldehyde-3-phosphate + sedoheptulose-7-phosphate
        • Reactants are produced by the two ribulose-5-phosphate reactions
        • Carbon-carbon rearrangement: 5-C + 5-C → 3-C + 7-C
        • Glyceraldehyde-3-phosphate can enter glycolysis (common intermediate)
      • Glyceraldehyde-3-phosphate + sedoheptulose-7-phosphate → [transaldolase] fructose-6-phosphate + erythrose-4-phosphate
        • Carbon-carbon rearrangement: 3-C + 7-C → 6-C + 4-C
        • Erythrose-4-phosphate used in aromatic amino acid synthesis
        • Fructose-6-phosphate can enter glycolysis (common intermediate)
      • Erythrose-4-phosphate + Xylulose-5-phosphate → [transketolase] glyceraldehyde-3-phosphate + fructose-6-phosphate
        • Carbon-Carbon rearrangement: 4-C + 5-C → 3-C + 6-C
        • Erythrose-4-phosphate is produced by the transaldolase reaction
        • Glyceraldehyde-3-phosphate and fructose-6-phosphate can enter glycolysis (common intermediate)