Integration of Metabolism lect 6 biochem 1404

Citric Acid Cycle and Oxidative Phosphorylation

• Acetyl CoA is the common metabolite produced from different fuel sources.
• It enters the citric acid cycle and gets oxidized to CO2.
• Most of the energy is trapped in the form of NADH and FADH2.
• Oxidative phosphorylation: NADH and FADH2 are oxidized in the electron transport chain, generating ATP.

Hexose Monophosphate Shunt

• Concerned with the liberation of NADPH.
• NADPH is utilized for biosynthesis of several compounds, including fatty acids and ribose sugar.
• Ribose sugar is an essential component of nucleotides.

Gluconeogenesis

• Many non-carbohydrate compounds serve as precursors for gluconeogenesis.
• Glucose is synthesized from these precursors.

Glycogen Metabolism

• Glycogen is the storage form of glucose in liver and muscle.
• Glycogen serves as a fuel reserve to meet body needs for a brief period.

Regulation of Metabolic Pathways

• Metabolic pathways are controlled by four mechanisms:
  • Availability of substrates
  • Covalent modification of enzymes
  • Allosteric regulation
  • Regulation of enzyme synthesis

Integration of Metabolism during Fed State

• Insulin is the hormone responsible for controlling metabolism in various organs of the body.
• The liver, muscle, and adipose tissue work together to meet the body's metabolic demands.

Carbohydrate, Lipid, and Protein Metabolism during Fasting

• Glucose production and utilization:
  • Liver: Glucose production increases through gluconeogenesis.
  • Adipose tissue: Glucose uptake and metabolism decrease.
  • Skeletal muscle: Glucose uptake and metabolism decrease.
  • Brain: Glucose is the primary fuel source.
• Lipid metabolism:
  • Adipose tissue: Lipolysis increases, releasing fatty acids (FA) and glycerol.
  • Skeletal muscle: FA and ketone bodies are utilized as fuel.
  • Liver: FA oxidation increases, and ketone bodies are produced.
• Protein metabolism:
  • Skeletal muscle: Muscle proteins are degraded, and amino acids are utilized for glucose synthesis in the liver.
  • Liver: Amino acids are utilized for glucose synthesis.

Brain Metabolism during Fasting

• In the early phase of starvation, the brain depends on glucose supplied by liver gluconeogenesis.
• In prolonged starvation, ketone bodies replace glucose as the primary fuel for the brain.
• This reduces protein catabolism.

Integration of Metabolism during Fasting

• The liver, muscle, and adipose tissue work together to meet the body's metabolic demands during fasting.
• The metabolism is reorganized to meet the new demands of fasting.
• Glucose is the fuel of choice for brain and muscle.
• Protein meets the fuel demands of the body.
• Triacylglycerol (TG) of adipose tissue is the predominant energy reserve of the body.

Liver during Fasting

• Carbohydrate metabolism:
  • Increased glycogen degradation and gluconeogenesis.
  • Complete dependence on hepatic gluconeogenesis from lactate and alanine.
• Lipid metabolism:
  • Increased FA oxidation and ketone body formation.
  • Ketone bodies meet the fuel demands of the brain.