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Metabolism of Carbohydrates: GLUT'S AND GLYCOLYSIS

1. Major Carbohydrates in the Human Body and Diet

  • Monosaccharides (1 sugar unit)

    • Glucose → main blood sugar, primary fuel.

    • Fructose → fruit sugar, metabolized mostly in liver.

    • Galactose → from milk sugar (lactose), converted to glucose in liver.

  • Disaccharides (2 sugar units)

    • Sucrose = glucose + fructose → table sugar.

    • Lactose = glucose + galactose → milk sugar.

    • Maltose = glucose + glucose → from starch digestion.

  • Polysaccharides (many sugar units)

    • Starch → plant storage form, main dietary polysaccharide.

    • Glycogen → human storage form, in liver (blood glucose regulation) & muscle (energy for contraction).

    • Fiber (cellulose) → indigestible, adds bulk.

2. Glucose Absorption in the Intestine

Process:

  • Step 1: In small intestine, glucose enters epithelial cell from gut lumen via SGLT1 (sodium-glucose transporter, uses Na+ gradient).

  • Step 2: Glucose exits into blood via GLUT2 (facilitated diffusion).

  • Step 3: Na+/K+ ATPase maintains sodium gradient.

Diagram (mental picture):

  • Lumen → SGLT1 → Epithelial cell → GLUT2 → Blood.

  • Na+/K+ ATPase at basolateral side keeps process running.

3. Glucose Transporters (GLUTs)

  • Definition: Proteins that move glucose across membranes (facilitated diffusion, no ATP).

  • Types and Tissues:

    • GLUT1: RBCs, brain — constant uptake (basal glucose).

    • GLUT2: Liver, pancreas, intestine — bidirectional (important for sensing & releasing glucose).

    • GLUT3: Neurons — high affinity (always get glucose).

    • GLUT4: Muscle, adipose — insulin-dependent.

  • Function: Ensure each tissue gets glucose according to its needs.

4. Glycolysis (Overview)

  • Purpose: Break down glucose → ATP + intermediates for biosynthesis.

  • Reactants: 1 glucose + 2 NAD+ + 2 ADP + 2 Pi.

  • Products: 2 pyruvate + 2 NADH + 2 ATP (net).

  • Location: Cytoplasm of all cells.

  • Distribution: Everywhere, but very important in brain, RBCs, muscle.

5. Key Enzymes of Glycolysis

  • Hexokinase / Glucokinase

    • Function: Phosphorylates glucose → glucose-6-P (traps it inside cell).

    • Deficiency: Can cause hypoglycemia (can’t trap glucose).

  • Phosphofructokinase-1 (PFK-1)

    • Function: Rate-limiting step, commits glucose to glycolysis.

    • Deficiency: Rare, can cause exercise intolerance.

  • Pyruvate kinase

    • Function: Final step, makes ATP + pyruvate.

    • Deficiency: Hemolytic anemia (RBCs depend only on glycolysis for ATP).

6. Regulation of Glycolysis

  • Allosteric regulation

    • ATP = inhibits; AMP/ADP = activates.

    • Citrate = inhibits PFK-1.

    • Fructose-2,6-bisphosphate = powerful activator of PFK-1.

  • Hormonal regulation

    • Insulin ↑ glycolysis (activates PFK-1 via ↑F2,6BP).

    • Glucagon ↓ glycolysis (via PKA, lowers F2,6BP).

  • Covalent modification

    • Phosphorylation/dephosphorylation (especially in liver enzymes).

7. Hexokinase vs. Glucokinase

  • Hexokinase

    • Location: All tissues (except liver, pancreas β-cells).

    • High affinity (works even at low glucose).

    • Always active (baseline trapping of glucose).

  • Glucokinase

    • Location: Liver, pancreas.

    • Low affinity, high capacity (active when glucose is high, e.g., after meal).

    • Acts as a glucose sensor.

8. Aerobic vs. Anaerobic Glycolysis

  • Aerobic

    • Location: Most tissues (brain, liver, muscle).

    • Products: 2 pyruvate → mitochondria (→ acetyl-CoA, TCA, oxidative phosphorylation).

    • ATP yield: Much higher (30–32 ATP per glucose).

  • Anaerobic

    • Location: RBCs, exercising muscle, some tissues with low O₂.

    • Products: 2 lactate + 2 ATP.

    • Purpose: Generate ATP quickly, regenerate NAD+ for glycolysis.