Metabolism

Metabolism

Fundamentals of Energy Balance

  • Components of metabolism include:

    • Membrane transport

    • Mechanical work

    • Chemical work

    • Synthesis of short-term energy storage (ATP) and long-term energy storage (glycogen, fat)

  • Energy in vs. Energy out:

    • Energy stored in fat is labeled as 'E in'

    • Energy expenditure through:

    • Resting metabolic rate (30-60%)

    • Physical activity (10-60%)

    • Thermic effect of food (~10%)

  • Energy intake is determined by:

    • Absorptive efficiency, where nutrients are oxidized (carbohydrates, proteins, and fats)

Topics Addressed in Unit

  • Distinguish between:

    • Fed (absorptive) state

    • Fasted (postabsorptive) state

  • Describe homeostatic control of metabolism:

    • Explain the roles of insulin and glucagon

    • Develop a response map for type 1 diabetes showing body responses to elevated plasma glucose without insulin presence.

Fed State (Absorptive State)

  • Definition:

    • Occurs following a meal.

    • Products of digestion are absorbed, utilized, and stored.

  • Characterized as an anabolic state.

Fed State: Nutrient Pools and Metabolism

  • Fats:

    • Free fatty acids + glycerol

    • Process: Lipogenesis from dietary fats.

  • Carbohydrates:

    • Process: Glycogenesis from glucose.

  • Proteins:

    • Process: Protein synthesis from amino acids.

  • Metabolic pathways include:

    • Lipogenesis (formation of fat)

    • Glycogen stores

    • Lipolysis (break down of fats)

    • Glycogenolysis (break down of glycogen)

    • Gluconeogenesis (synthesis of glucose)

Energy Regulation in Fed State

  • Most plasma glucose is utilized for immediate energy production or stored as glycogen:

    • Liver glycogen regulates blood glucose levels.

    • Muscle glycogen is utilized for muscle contraction.

  • Questions for study:

    • What happens to excess carbohydrates consumed?

    • What happens when consuming excess protein (e.g., protein shake)?

Fat Metabolism in Fed State

  • Key points include:

    • Lipoprotein lipase facilitates the uptake of free fatty acids for immediate energy or storage.

    • Free fatty acids can be derived from triglycerides in adipose tissue.

Fasted State (Postabsorptive State)

  • Definition:

    • Follows complete digestion of a meal when nutrients are distributed.

    • Characterized by declining plasma glucose levels and a catabolic state.

  • Energy Production Sources:

    • Liver glycogen converts to glucose.

    • Fatty acids and glycerol from adipose tissue enter the bloodstream.

    • Muscle glycogen becomes energy or is supplemented by free fatty acids and amino acids.

Glycogen Metabolism in Fasted State

  • In the liver, glycogen is converted to glucose via glycogenolysis, while muscles predominantly use fatty acids and proteins for energy due to muscle-specific metabolic pathways.

  • The absence of glucose-6-phosphatase in muscles results in different metabolic pathways between liver and muscle glycogen.

Homeostatic Control of Metabolism

  • Involves secretion of insulin and glucagon from the endocrine pancreas:

    • Insulin:

    • Functions as the hormone regulating energy usage and storage.

    • Glucagon:

    • Responsible for promoting energy release.

  • Metabolism is primarily regulated by the insulin-glucagon ratio.

Signals for Secretions of Insulin and Glucagon

  • Insulin secretion is stimulated by:

    • High plasma glucose levels

    • High plasma amino acid levels

  • Glucagon secretion is stimulated by:

    • Low plasma glucose levels

    • High plasma amino acid levels

  • Amino acids’ dual role in triggering both insulin and glucagon relates to their influence on energy balance.

Insulin Functions in Fed State

  • Mechanisms include:

    • Insulin secretion is initiated by:

    • Meal ingestion and nutrient absorption, particularly carbohydrates in the GI tract.

    • Stretch receptors in the GI tract that send sensory neuron input to the CNS.

  • Key functions include:

    • Increased transport of glucose, amino acids, and potassium into insulin-sensitive cells.

    • Stimulation of protein synthesis and inhibition of protein degradation.

    • Activation of glycolytic enzymes and glycogen synthase, inhibiting phosphorylase and gluconeogenic enzymes.

Clinical Cases: Diabetes Mellitus

  • Type 1 Diabetes:

    • Characterized by insulin deficiency due to pancreatic beta-cell destruction.

    • Genetic factors involved in major histocompatibility complex on chromosome 6.

  • Type 2 Diabetes:

    • Involves insulin resistance where target cells do not respond effectively to insulin.

    • Concordance rate of ~90% with various genetic defects such as in glucokinase or insulin receptors.

Important Questions and Considerations

  • Clicker Questions on insulin secretion:

    • Conditions leading to increased insulin secretion include elevated plasma glucose and amino acid levels, and the secretion of gastrointestinal peptides (e.g., GLP-1, GIP).

    • In contrast, sympathetic activation typically decreases insulin secretion.

  • Practice inquiry into responses following carbohydrate ingestion in insulin-deficient diabetes, focusing on metabolism outcomes such as protein degradation and gluconeogenesis.