Metabolic States Notes

Metabolic States

Homeostasis vs. Equilibrium

  • Equilibrium: Generally seen as undesirable in biochemistry because it's a fixed state. It prevents energy storage and excitable environments.
  • Homeostasis: A physiological tendency toward a relatively stable state. It's actively maintained and adjusted, often requiring energy expenditure.
  • Biochemists aim for homeostasis, maintaining compounds at levels different from equilibrium to store potential energy (e.g., sodium concentration gradient in neurons).
  • Homeostasis allows reactions to proceed while delaying equilibrium.

Nutritional States and Fuel Metabolism

  • Fuel metabolism pathways depend on an organism's nutritional state.
  • Transitions between fuel storage/mobilization and shifts among fuel types are pronounced during:
    • Well-fed state
    • Overnight fast
    • Prolonged starvation

Key Metabolic Pathways (Referenced)

  • Glycolysis, glycogenolysis, glycogenogenesis, gluconeogenesis, and pentose phosphate pathway (Chapter 9).
  • Citric acid cycle, electron transport chain, and oxidative phosphorylation (Chapter 10).
  • Fatty acid and cholesterol synthesis, beta-oxidation, ketogenesis, and ketolysis, amino acid metabolism (Chapter 11).

Postprandial (Absorptive or Well-Fed) State

  • Occurs shortly after eating, lasting 3-5 hours.
  • Characterized by:
    • Increased anabolism (synthesis of biomolecules)
    • Fuel storage
    • Catabolism (breakdown) for energy
  • Nutrients enter the liver via the hepatic portal vein and are either stored or distributed.
  • Insulin Release:
    • Blood glucose rises, stimulating insulin release.
    • Major target tissues: liver, muscle, and adipose tissue.
  • Insulin's Effects:
    • Promotes glycogen synthesis in the liver and muscle.
    • Excess glucose is converted to fatty acids and triacylglycerols in the liver when glycogen stores are full.
    • Promotes triacylglycerol synthesis in adipose tissue.
    • Promotes protein synthesis and glucose entry in muscle.
  • Liver primarily uses excess amino acid oxidation for energy.
  • Insulin-Insensitive Tissues:
    • Nervous tissue: Derives energy from oxidizing glucose to CO2CO_2 and water in well-fed and normal fasting states; ketones are used during prolonged fasting.
    • Red blood cells: Use glucose anaerobically regardless of metabolic state.

Postabsorptive (Fasting) State

  • Counterregulatory Hormones: Glucagon, cortisol, epinephrine, norepinephrine, and growth hormone oppose insulin's actions.
  • Liver:
    • Glycogen degradation and glucose release are stimulated.
    • Hepatic gluconeogenesis is stimulated by glucagon but slower than glycogenolysis (gluconeogenesis takes about 12 hours to reach max velocity).
  • Skeletal Muscle and Adipose Tissue:
    • Amino acid release from skeletal muscle and fatty acid release from adipose tissue are stimulated by decreased insulin and increased epinephrine.
    • Amino acids and fatty acids provide carbon skeletons and energy for gluconeogenesis in the liver.

Prolonged Fasting (Starvation)

  • Glucagon and epinephrine levels are markedly elevated.
  • High glucagon/insulin ratio leads to rapid liver glycogen degradation.
  • Gluconeogenesis becomes the primary source of glucose after about 24 hours.
  • Lipolysis:
    • Rapid lipolysis results in excess acetyl CoA.
    • Acetyl CoA is used for ketone body synthesis.
  • Fuel Utilization:
    • Muscle tissue uses fatty acids as its primary fuel.
    • The brain adapts to using ketones for energy (approximately two-thirds ketones and one-third glucose after several weeks).
  • Ketone utilization reduces the need for amino acid degradation, sparing vital proteins.
  • Red blood cells continue to depend on glucose due to the lack of mitochondria.