02: Carbohydrate Metabolism: Glycolysis and Gluconeogenesis - Study Notes

  • Carbohydrate Metabolism Overview

  • Focus on Glycolysis and Gluconeogenesis.

  • Presented by Dr. Anand Sridhar, Medical Biochemistry II.

  • Section Objectives

  • Stages of carbohydrate digestion in the GI tract.

  • Glucose transport mechanisms and glucose transporters (GLUT).

  • Definition and process of glycolysis.

  • Enzymes, reactants, products, and reaction types involved in glycolysis.

  • Energetics and hormonal regulation of glycolysis.

  • Fermentation processes and chemical fates of pyruvate.

  • Carbohydrate Digestion

  • Salivary Amylase:

    • Cleaves α-(1,4)- glycosidic bonds; inactivated by stomach acid.
    • Pancreatic secretions neutralize stomach acid, leading to the breakdown of oligosaccharides to monosaccharides.
    • Monosaccharides enter portal circulation; glucose stored as glycogen in the liver.

  • Glucose

  • A hexose monosaccharide and major carbohydrate form absorbed by the body.

  • Essential energy source for the brain (20% oxygen consumption, 25% glucose utilization).

  • Uptake into cells via glucose transporters (GLUT).

  • Glucose Transport

  • Cannot diffuse directly into cells; requires transport mechanisms.

  • Facilitated Diffusion:

    • Na+-independent and Na+-dependent transport includes two GLUT types:
    • Na+-independent: GLUT family.
    • Na+-dependent: SGLT (Sodium-dependent glucose transporters).

  • GLUT Transporters

  • GLUT1: Most tissues; basal glucose uptake.

  • GLUT2: Liver, kidneys, pancreas; insulin-sensitive.

  • GLUT3: Brain; low-level glucose transport.

  • GLUT4: Muscle and adipose; translocates in response to insulin.

  • GLUT5: Small intestine; fructose transporter.

  • Glycolysis

  • Main metabolic pathway for glucose breakdown, occurs in the cytosol of all cells.

  • Process summary:

    • 1 glucose (6 carbons) → 2 pyruvate (3 carbons) + energy.
      • -

  • Investment Phase: Steps

    1. Hexokinase: Glucose → Glucose 6-phosphate (ATP investment).
    2. Phosphoglucose Isomerase: Converts Glucose 6-P to Fructose 6-P.
    3. Phosphofructokinase-1 (PFK-1): Fructose 6-P → Fructose 1,6-bisphosphate (regulated and irreversible).
    4. Aldolase: Cleavage of Fructose 1,6-P to glyceraldehyde 3-phosphate (G3P) and dihydroxyacetone phosphate (DHAP).
    5. Triose Phosphate Isomerase: Interconversion of DHAP and G3P, leading to G3P accumulation.
    6. Dehydrogenase Reaction: G3P to 1,3-bisphosphoglycerate (NAD+ to NADH).
    7. Phosphoglycerate Kinase: Forms ATP from ADP (substrate level phosphorylation).
    8. Mutase: 3-phosphoglycerate → 2-phosphoglycerate (isomerization).
    9. Enolase: 2-phosphoglycerate → phosphoenolpyruvate (PEP).
  1. Pyruvate Kinase: PEP → Pyruvate + ATP (final product).

  • Energetics of Glycolysis

  • Investment Phase: 2 ATP used.

  • Payoff Phase: 4 ATP produced and 2 NADH; net gain = 2 ATP.

  • Hormonal Regulation of Glycolysis

  • Insulin promotes glycolysis; glucagon inhibits it.

  • Activation of key enzymes when nutrient-rich (carb-rich diet).

  • Lactate Fermentation

  • In absence of oxygen, pyruvate reduced to lactate (Cori Cycle).

  • Important for regenerating NAD+, allowing glycolysis to continue in anaerobic conditions.

  • Alternate fates of Pyruvate

  • Acetyl CoA formation for TCA cycle.

  • Carboxylation to oxaloacetate for gluconeogenesis.

  • Reduction to ethanol in fermentation processes.

  • Gluconeogenesis

  • Synthesis of glucose from non-carbohydrate sources: pyruvate, lactate, etc.

  • Mostly occurs in the liver; key aerobic process.

  • Begins with pyruvate → oxaloacetate → phosphoenolpyruvate through several key enzymatic steps.

  • Key steps and enzymes:

    • Pyruvate Carboxylase marks starting point in mitochondria.
    • Fructose 1,6-bisphosphatase regulates steps opposing those of glycolysis.
    • Glucose 6-phosphatase finalizes gluconeogenesis.

  • Cori Cycle

  • Lactate from muscle can be recycled into glucose in the liver, maintaining glucose supply during fasting or intense exercise.