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HMP Shunt, NADPH & Simple Sugar 2025

1. Pentose Phosphate Pathway (PPP)

  • Definition: Also known as the hexose monophosphate (HMP) shunt, this pathway occurs in the cytosol and operates parallel to glycolysis.

  • Purpose:

    • Generates NADPH for reductive biosynthesis and antioxidant defense.

    • Produces ribose-5-phosphate for nucleotide and nucleic acid biosynthesis.

    • Provides intermediates linking to glycolysis.

  • Key Features:

    • Comprises two phases:

      1. Irreversible Oxidative Reactions (produce NADPH).

      2. Reversible Non-Oxidative Reactions (interconversion of sugars).

    • No ATP is directly consumed or produced.

2. Irreversible Oxidative Reactions

  1. Dehydrogenation of Glucose-6-Phosphate:

    • Enzyme: Glucose-6-phosphate dehydrogenase (G6PD).

    • Product: 6-Phosphogluconate and the first NADPH molecule.

    • Regulation: Inhibited by high NADPH/NADP⁺ ratio.

  2. Formation of Ribulose-5-Phosphate:

    • Enzyme: 6-Phosphogluconate dehydrogenase.

    • Products: Ribulose-5-phosphate, CO₂, and the second NADPH molecule.

3. Reversible Non-Oxidative Reactions

  • Purpose: Interconversion of sugars (3C–7C).

  • Enzymes:

    • Transketolase: Transfers 2-carbon units (requires TPP).

    • Transaldolase: Transfers 3-carbon units.

  • Key Intermediates:

    • Ribulose-5-phosphate → Ribose-5-phosphate, Fructose-6-phosphate, Glyceraldehyde-3-phosphate.

  • Flexibility: Depends on cellular needs for NADPH or ribose-5-phosphate.

4. Functions and Uses of NADPH

  1. Reductive Biosynthesis:

    • Provides reducing equivalents for fatty acid and cholesterol synthesis.

  2. Reduction of Hydrogen Peroxide (H₂O₂):

    • Maintains reduced glutathione (GSH), detoxifying reactive oxygen species (ROS).

    • Catalyzed by glutathione reductase using NADPH.

  3. Cytochrome P450 Monooxygenase System:

    • Involved in steroid hormone biosynthesis, bile acid synthesis, and detoxification of xenobiotics.

  4. Phagocytosis:

    • NADPH oxidase generates superoxide radicals for microbial killing (respiratory burst).

  5. Synthesis of Nitric Oxide (NO):

    • NO synthase uses NADPH to produce NO, a vasodilator and signaling molecule.

5. G6PD Deficiency

  • Definition: Inherited condition causing hemolytic anemia due to insufficient NADPH production.

  • Clinical Features:

    • Hemolysis under oxidative stress (e.g., infection, drugs, fava beans).

    • Neonatal jaundice.

  • Precipitating Factors:

    • Oxidant drugs: Antibiotics, antimalarials, antipyretics.

    • Favism: Hemolysis triggered by fava bean consumption.

    • Infections: Generate oxidative stress in erythrocytes.