Biomed Chem Lecture 2

Clinical Laboratory Chemistry: Regulation and Abnormal Carbohydrate Metabolism

Lecture 2 Outline

  • Topics covered
    • Regulation of carbohydrate (CHO) metabolism
    • Diet
    • Energy source
    • Hormones
    • Organ systems
    • Metabolic response to
    • Eating
    • Fasting
    • Starvation
    • Tissue breakdown
    • Disorders of CHO metabolism
    • Hypoglycemia
    • Hyperglycemia
    • Inborn errors of CHO metabolism

Factors Regulating CHO Metabolism

  1. Dietary Source and Excess

    • Glucose:
      • Glycogenesis: Converts glucose to glycogen, stored in liver and muscles.
      • Glycerol: Converted to lipids and stored in adipose tissue.
    • Amino Acids (AA): Role in protein synthesis.
    • Fatty Acids (FA) + Glycerol: Form triglycerides (TG) stored in adipose tissue.

  2. Energy Stores

    • Caloric Values:
      • Carbohydrates: 4.1 kcal/g
      • Proteins: 4.1 kcal/g
      • Lipids: 9.3 kcal/g
    • Effect of starvation on food stores in the body.

  3. Hormones

    • Key hormones affecting blood glucose levels and metabolism.

  4. Organ Systems

    • Different organ systems play critical roles in CHO metabolism.

Nutritional Sources and Energy Metabolism

  1. Diet Source and Excess of Nutrients
    • Glycolysis: Breakdown of glucose to produce energy (ATP).
    • Citric Acid Cycle: Metabolic pathway to further oxidize acetyl-CoA.
    • Oxidative Phosphorylation: Generates ATP through electron transport chain.
    • Glycogenesis, Glycogenolysis, Gluconeogenesis: Processes related to glucose storage and utilization.
    • Lipogenesis, Lipolysis: Processes of fat storage and breakdown.
    • Fatty Acid Oxidation: Pathway for energy production from fats.

Energy Stores

  • Glycogen
    • Polysaccharide stored in the liver and muscle; available for short-term use (24-36 hours).
  • Proteins
    • Used as an energy reserve; degradation begins after prolonged fasting.
  • Lipids
    • Major energy reserve; oxidation provides significant fuel and can lead to ketone body accumulation during starvation.

Ketogenesis, Ketonemia, and Ketosis

  • Ketone Bodies
    • Includes acetone, acetoacetic acid, and beta-hydroxybutyric acid; form during fat breakdown when glucose is not available.
  • Ketonemia: Presence of ketone bodies in the blood leading to lowered blood pH that must be compensated by buffers.
  • Ketosis: Elevated levels of ketone bodies in body fluids, potentially leading to ketoacidosis if severe.

Hormonal Regulation of Blood Glucose

  • Insulin: Decreases blood glucose levels; secreted by pancreatic beta cells when glucose is high.
  • Glucagon: Increases blood glucose levels; secreted by pancreatic alpha cells when glucose is low.
  • Other hormones include catecholamines, glucocorticoids, thyroid hormones, and growth hormone affecting blood glucose levels.

Actions of Insulin and Glucagon

Insulin Actions
  • Promotes glucose uptake by cells, increases ATP production, enhances glycogen synthesis, decreases gluconeogenesis, and stimulates protein and fat synthesis.
  • Mechanism of Action: Insulin acts via binding to receptors that activate glucose transport into cells.
Glucagon Actions
  • Promotes gluconeogenesis, increases glycogen breakdown, stimulates fat breakdown in adipose tissue.
  • Mechanism involves G protein-coupled receptors leading to increased c-AMP and protein kinase activity.

Organ Systems in CHO Metabolism

  1. Intestine
    • Site of CHO digestion and absorption.
  2. Liver
    • Main site for glucose storage and production. 90% of gluconeogenesis occurs here.
  3. Muscle
    • Significant glycogen storage but cannot export glucose to other cells.
  4. Kidney
    • Small glycogen stores, mainly reabsorbs glucose.

Metabolic Response to Eating, Fasting, Starvation, and Tissue Breakdown

  • Fed State
    • Elevated insulin, decreased glucagon; focus on energy storage.
  • Fasting State
    • Increased glucagon, decreased insulin; focus on maintaining blood glucose via glycogenolysis and gluconeogenesis.
  • Starvation
    • Very low insulin levels and increased ketone body usage as fuel.
  • Tissue Breakdown
    • Associated with trauma, infection; leads to protein catabolism and altered metabolic response.

Carbohydrate Disorders

Blood Glucose Levels
  • Normal fasting: 70-110 mg/dl (3.8-6.1 mmol/L)
  • Impaired glucose tolerance: 110-126 mg/dl (6.1-7.0 mmol/L)
  • Diabetes: >126 mg/dl (>7.0 mmol/L
Hypoglycemia
  • Defined as blood glucose <70 mg/dl, caused by various factors such as prolonged fasting, excessive insulin, or hormonal deficiencies.
  • Symptoms include hunger, fatigue, confusion, and in extreme cases, coma.
Hyperglycemia
  • Defined as blood glucose >180 mg/dl; relates to diabetes mellitus.
  • Types of DM: Type 1 (IDDM), Type 2 (NIDDM), Gestational.
Inborn Errors of Carbohydrate Metabolism
  • Conditions like glycogen storage diseases, galactosemia.
  • Impact metabolic function significantly and usually exhibit symptoms in infancy or childhood.