Carbohydrate Metabolism

Carbohydrate Metabolism Overview

  • Key Processes: Understanding carbohydrate metabolism involves multiple processes including glycolysis (both aerobic and anaerobic), gluconeogenesis, glycogenesis, and glycogenolysis.

Learning Outcomes

  • Describe the process of aerobic and anaerobic glycolysis.

  • Explain the enzymatic regulation of glycolysis.

  • Understand the metabolism of fructose and the consequences of aldolase and fructokinase deficiencies.

  • Discuss the role of glycogen in metabolism.

  • Differentiate carbohydrate metabolism in fed vs. fasting states.

  • Identify sources of energy available during fed and fasting states.

  • Describe the role of ketone bodies.

  • Explain the roles of insulin, glucagon, and other counter-regulatory hormones in the control of metabolism.

Fructose Metabolism

  • Fructose as a Nutrient:

    • Contributes to about 10% of dietary calories, primarily from fruit and sucrose (disaccharide comprising glucose and fructose).

    • Transport: Uptake into cells mediated by GLUT5 transporter.

    • Processed predominantly in the liver; does not stimulate insulin secretion.

  • Metabolic Pathway:

    • Fructose is converted into Fructose 1-P by fructokinase.

    • Can be further broken down by Aldolase B to produce intermediate metabolites such as Glyceraldehyde and Dihydroxyacetone Phosphate (DHAP).

    • The process continues through gluconeogenic intermediates to yield pyruvate.

  • Disorders of Fructose Metabolism:

    • Essential Fructosuria: Caused by the deficiency of fructokinase; leads to benign condition with fructose accumulation in urine.

    • Hereditary Fructose Intolerance (HFI): Caused by deficiency of aldolase B; symptoms include convulsions, irritability, and hypoglycemia exacerbated by fructose/sucrose intake.

Glycogen Metabolism

  • Role of Glycogen:

    • Liver glycogen: 100g in well-fed state; crucial for maintaining blood glucose levels during fasting.

    • Muscle glycogen: 400g; serves primarily as energy source during strenuous exercise but is not available for other tissues.

  • Processes:

    • Glycogenesis: Process of glycogen synthesis during fed state, promoted by insulin.

    • Glycogenolysis: Breakdown of glycogen during fasting, promoted by glucagon.

  • Key Enzymes:

    • Glycogen synthase (active when dephosphorylated, inactive when phosphorylated) and glycogen phosphorylase (active when phosphorylated).

Gluconeogenesis

  • Process: The synthesis of glucose from non-carbohydrate sources during prolonged fasting. Initial substrates include:

    • Lactate, produced by exercising muscle.

    • Glycerol, derived from fat reserves (triacylglycerols).

    • Alpha-keto acids, produced from the catabolism of amino acids.

  • Key Points:

    • Occurs mainly in the liver (90%); some gluconeogenesis also occurs in the kidneys.

    • Involves multiple enzymes including PEP carboxykinase and pyruvate carboxylase, which are bypassed in glycolysis.

    • Requires energy, with ATP, GTP, and NADH being key energy sources.

  • Regulation:

    • Gluconeogenesis is activated by high glucagon and inhibited by insulin; it responds to changes in substrate availability and enzyme expression levels.

Summary of Key Enzymes

  • Fructose Metabolism:

    • Fructokinase (essential fructosuria)

    • Aldolase B (hereditary fructose intolerance)

  • Glycogenesis vs. Glycogenolysis:

    • Both processes regulated by insulin (promotes glycogenesis) and glucagon (promotes glycogenolysis).

  • Gluconeogenesis:

    • Involves reversing glycolysis with modifications, using lactate, alpha-keto acids, and glycerol as substrates.