Lecture 16 Glycogen Synthesis and Degradation FS

Overview of Exam and Lecture Plan

  • Exam 3 scheduled for one week from today

  • Lecture today may run over time; Thursday's lecture will be shorter

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Gluconeogenesis

Definition

  • Synthesis of glucose from pyruvate and other simple precursors

  • Functions as a crucial metabolic pathway when glucose is not readily available

Occurrence

  • Present in all animals, plants, fungi, microorganisms

  • Major site: liver (also occurs in kidneys, not in muscle cells)

Importance

  • Especially vital during fasting/starvation

    • Glucose is a primary fuel for the brain

    • Red blood cells rely solely on glucose for energy

Inputs and Outputs of Gluconeogenesis

Key Inputs

  • Blood glucose, glycoproteins, monosaccharides, sucrose, glycogen, glucose 6-phosphate

  • Amino acids, lactate, glycerol, pyruvate, and citric acid cycle intermediates

Output

  • Mainly produces glucose 6-phosphate in animals

  • In plants, outputs can involve energy storage processes

Enzymes of Gluconeogenesis

  • Important enzymes include:

    • Glucose 6-phosphatase

    • Phosphoglucose isomerase

    • Fructose 1,6-bisphosphatase

    • Aldolase

    • Triose phosphate isomerase

    • Glyceraldehyde 3-phosphate dehydrogenase

    • Phosphoglycerate kinase

    • Other various key enzymes connecting glycolysis and gluconeogenesis

Reciprocal Regulation of Gluconeogenesis and Glycolysis

Regulation Mechanism

  • Gluconeogenesis and glycolysis are reciprocally regulated in cells

  • Glycolysis occurs when glucose is abundant; gluconeogenesis is active when glucose is scarce

Liver-Specific Regulation

  • Fructose 6-phosphate, AMP, and citrate levels are key in regulating the pathways

    • High ATP: Slow down glycolysis, promote gluconeogenesis

    • High AMP: Urge glycolysis, inhibit gluconeogenesis

Role of Fructose 2,6-Bisphosphate

  • F2,6BP stimulates phosphofructokinase (glycolysis) and inhibits fructose 1,6-bisphosphatase (gluconeogenesis)

Hormonal Control of Glycogen Metabolism

Glucagon vs. Insulin

  • Glucagon: Increases blood glucose by stimulating glycogen breakdown, gluconeogenesis; secreted when glucose is low

  • Insulin: Lowers blood glucose by promoting uptake, glycolysis, and glycogenesis; secreted when glucose is high

Glycogen Synthase and Phosphorylase Regulation

  • Glycogen phosphorylase activation and glycogen synthase inactivation are influenced by hormonal signals

  • GSK3 inactivates glycogen synthase; insulin signaling inhibits GSK3 to promote glycogen synthesis

The Cori Cycle

Mechanism

  • Converts lactate produced in muscles during anaerobic conditions back into glucose in the liver

    • Lactate transported to liver during recovery

    • Glucose then released back into bloodstream to be used by muscles

Exercise and Glycogen

Glycogen Depletion

  • Fatigue correlates with glycogen reserves depletion

  • Immediate energy demands during physical activity cause rapid glycogen breakdown

Hormonal Responses to Exercise

  • During exercise, both glucagon and epinephrine levels rise, increasing glucose mobilization and usage

Diabetes Mellitus

Overview

  • Characterized by high blood glucose due to insulin insufficiency or resistance

  • Type 1 Diabetes: Insufficient insulin production due to autoimmune destruction of pancreatic cells

  • Type 2 Diabetes: Cells become resistant to insulin; typically associated with obesity

Symptoms and Complications

  • Common symptoms: excessive thirst, frequent urination

  • Long-term complications: kidney failure, cardiovascular disease, blindness