Carbohydrate Metabolism and Glycolysis

Carbohydrate Metabolism

• Digestion and Absorption of Dietary CHO:
  • Simple carbohydrates are absorbed by the small intestine.
  • Absorbed carbohydrates are transported to the liver and other tissues.
  • They are either converted into fatty acids, amino acids, or glycogen.
  • Alternatively, they are oxidized through catabolic pathways.

Glucose Metabolism (Glycolysis)

• Definition:
  • Glycolysis is the oxidation of glucose to either pyruvate or lactate.
  • It is a catabolic pathway.
  • Aerobic glycolysis produces pyruvate in the presence of oxygen.
  • Anaerobic glycolysis produces lactate in the absence of oxygen.
• Key Enzymes:
  • Hexokinase: Initiates glycolysis by phosphorylating glucose.
  • Glucokinase: Found in the liver, phosphorylates glucose only when blood glucose levels are high.
• Regulation:
  • Hexokinase: Allosterically regulated; irreversible.
  • Glucokinase: Inducible enzyme with a high Km for glucose.
• Energetics:
  • Aerobic glycolysis: Net yield of 7 ATP molecules per glucose molecule.
  • Anaerobic glycolysis: Net yield of 2 ATP molecules per glucose molecule.
• Fate of Pyruvate:
  • Aerobic glycolysis: Pyruvate enters the citric acid cycle.
  • Anaerobic glycolysis: Pyruvate is converted to lactate.

Citric Acid Cycle

• Definition:
  • A series of biochemical reactions that oxidize acetyl-CoA to carbon dioxide and water.
• Importance:
  • Generates ATP through oxidative phosphorylation.
  • Provides precursors for biosynthesis pathways.

Gluconeogenesis

• Definition:
  • The process of synthesizing glucose from non-carbohydrate precursors, primarily pyruvate, lactate, glycerol, and glucogenic amino acids.
  • It is an anabolic pathway.
• Importance:
  • Maintains blood glucose levels during fasting.
  • Supplies glucose to tissues like the brain.
  • Clears metabolic products from the blood.
• Regulation:
  • Allosteric regulation:
    • Acetyl-CoA activates pyruvate carboxylase.
    • AMP inhibits fructose-1,6-bisphosphatase.
  • Hormonal regulation:
    • Insulin inhibits gluconeogenesis.

Glycogen Metabolism

• Definition:
  • The process of synthesizing and breaking down glycogen, the storage form of glucose in animals.
• Glycogenesis:
  • The synthesis of glycogen from glucose.
• Glycogenolysis:
  • The breakdown of glycogen into glucose.
• Regulation:
  • Insulin: Stimulates glycogen synthesis.
  • Glucagon: Stimulates glycogen breakdown.

Blood Glucose Homeostasis

• Regulation:
  • Insulin:
    • Secreted by pancreatic β-cells in response to hyperglycemia.
    • Promotes glucose uptake by cells, glycogen synthesis, and inhibits gluconeogenesis.
  • Glucagon:
    • Secreted by pancreatic α-cells in response to hypoglycemia.
    • Stimulates glycogen breakdown and gluconeogenesis.
  • Growth Hormone:
    • Released from the pituitary gland.
    • Inhibits glucose uptake, promotes lipolysis, and increases protein synthesis.
  • Glucocorticoids:
    • Released from the adrenal cortex.
    • Inhibit glucose uptake, promote gluconeogenesis, and increase lipolysis.
  • Adrenaline:
    • Released from the adrenal medulla in response to stress.
    • Stimulates glycogen breakdown and lipolysis.

Pentose Phosphate Pathway (PPP)

• Definition:
  • An alternative pathway for glucose metabolism that generates NADPH and ribose-5-phosphate.
  • Primarily an anabolic pathway.
• Functions:
  • Provides NADPH for reductive biosynthesis.
  • Synthesizes ribose-5-phosphate for nucleotide and nucleic acid synthesis.
  • Metabolizes dietary pentose sugars.
• Medical Importance:
  • Glucose-6-Phosphate Dehydrogenase Deficiency (G6PDD):
    • A genetic deficiency that affects the activity of glucose-6-phosphate dehydrogenase (G6PD).
    • Can lead to hemolytic anemia due to oxidative stress in erythrocytes when individuals are exposed to certain drugs or infections.
    • NADPH deficiency in erythrocytes results in reduced glutathione levels, increasing oxidative stress.