Chapter 16 Glycogen metabolism and Gluconeogenesis lecture

Chapter 16: Glycogen Metabolism and Gluconeogenesis

Glycogen Breakdown

  • Glycogen:

    • Storage form of glucose in animals, fungi, and bacteria.

    • Glycogen is a branched polymer that ensures a constant supply of glucose for the brain and red blood cells (RBCs).

    • Glucose mobilization in the liver involves:

      • Conversion pathway: Glycogen → Glucose-1-Phosphate (G1P) → Glucose-6-Phosphate → Glucose.

  • Enzyme Deficiencies:

    • McArdle’s disease: Caused by deficiencies in enzymes responsible for glycogen degradation.

  • Role of Liver and Kidney:

    • Glucose-6-Phosphate (G6P) is converted to glucose in the liver and kidney, then released into the bloodstream.

Overview of Glucose Metabolism

  • Pathways:

    • Glycogen Breakdown

    • Glycogen Synthesis

    • Pentose Phosphate Pathway:

      • Produces ribose-5-phosphate, critical for nucleic acid synthesis.

    • Glycolysis: Breakdown of glucose.

    • Gluconeogenesis: Formation of glucose from non-carbohydrate sources.

    • Products and precursors include Pyruvate, Amino Acids, Lactate, and Acetyl-CoA, leading into the Citric Acid Cycle.

Structure of Glycogen

  • Glycogen consists of:

    • Branching: a(1→6) linkages create a branched structure for efficient energy release.

    • Nonreducing and Reducing Ends: The structure allows rapid release of glucose from many ends.

Glycogenolysis (Glycogen Breakdown)

  • Process involves several enzymes:

    • Glycogen phosphorylase: Converts glycogen to G1P.

    • Glycogen debranching enzyme: Specifically targets a(1→6) linkages to facilitate breakdown.

    • Phosphoglucomutase: Converts G1P to G6P.

Glycogen Debranching Enzyme

  • Function and Mechanism:

    • Phosphorolysis: Cuts glycogen branches, producing G1P.

    • Glucosyltransferase: Moves trisaccharides to allow further breakdown.

    • Contains separate active sites for transferase and glucosidase activities.

Glycogen Synthesis

  • Glycogen Synthesis Process:

    • Begins with the conversion of glucose to glucose-6-phosphate, then into UDP-glucose, finally forming glycogen.

    • Glycogenin acts as a primer for glycogen synthesis.

Control of Glycogen Metabolism

  • Regulation via hormonal control (insulin, glucagon, epinephrine) and allosteric interactions.

  • Opposing pathways: Synthesis is regulated to balance degradation, ensuring energy homeostasis.

Allosteric Control

  • Key effectors include ATP, G6P, and AMP, which toggle enzyme activity based on cellular energy status.

  • Glycogen phosphorylase is activated by AMP and inhibited by ATP and G6P.

  • Glycogen synthase is activated by G6P.

Enzymatic Regulation Cascade

  • Glycogen Phosphorylase Activation:

    • Involves phosphorylase kinase (phosphorylates), protein kinase A (PKA), and dephosphorylation by protein phosphatase 1 (PP1).

Hormonal Control of Glycogen Metabolism

  • Key hormones include:

    • Insulin: Promotes glycogen synthesis.

    • Glucagon and Epinephrine: Stimulate glycogen degradation.

  • Mechanisms involve cAMP as a second messenger affecting enzyme phosphorylation.

Gluconeogenesis

  • Synthesis of glucose from non-carbohydrate precursors mainly in the liver.

  • Key substrates: lactate, pyruvate, and amino acids; metabolic bypass of certain glycolytic enzymes.

  • Regulation: Gossip with glycolysis, ensuring opposite processes are tightly controlled.

Importance of Precursors

  • Non-carbohydrate precursors must convert to oxaloacetate; fatty acids don’t convert into glucose in animals (yield acetyl-CoA).

Pyruvate Conversion to PEP

  • Critical steps:

    1. Pyruvate carboxylase.

    2. PEP carboxykinase (PEPCK); both critical in gluconeogenesis.

Other Carbohydrate Biosynthetic Pathways

  • Glycosidic bond formation and protein modification through glycosylation processes.

  • Lactose synthesis involves UDP-linked sugars.

  • Various nucleotide sugar donors are utilized in mammalian and plant carbohydrate synthesis.