BIOC2600 1.9

• Catabolism of carbohydrates, fatty acids and amino acids converge in the liver.
• Fed liver is different from fasting liver in terms of its function.
• The reactions involved in the replenishment of intermediates of the TCA cycle depleted by biosynthesis are outlined.
• The metabolism of different biomolecules in the liver is discussed.
• Metabolic cooperation between skeletal muscle and liver is explained.
• The metabolic state in well-fed vs fasting liver is compared and contrasted.
• Intermediates of the TCA cycle can be syphoned out for biosynthesis of carbohydrates, lipids and amino acids, as well as other biomolecules.
• Oxaloacetate can be taken out from the TCA cycle to make carbohydrates.
• Citrate can be removed for the biosynthesis of lipids.
• Oxaloacetate and a-ketoglutarate can be used for biosynthesis of amino acids.
• If these TCA cycle intermediates are syphoned out for biosynthesis, there might not be enough intermediates to complete the TCA cycle.
• If there are not enough intermediates available to complete the TCA cycle, there will not be enough oxaloacetate to react with acetyl-CoA to form citrate.
• As a result, the acetyl-CoA metabolism will slow down and the rate of formation of ATP downstream will slow down.
• These intermediates must be replenished for the cycle and the central metabolic pathway to continue.
• They are replenished by anaplerotic reactions.
• Most cells have the enzymes to carry out both catabolic and anabolic reactions of the important biomolecules (carbohydrates, lipids and proteins).
• Catabolic and anabolic pathways are reciprocally regulated.
• When one pathway is active the other is suppressed.
• Catabolic and anabolic pathways that connect the same 2 end points may share many of the same enzymes but at least one of the steps use different enzymes in the catabolic and anabolic direction.
• These enzymes will serve as the site of regulation.
• During recovery, lactate is transported to the liver and converted to glucose by gluconeogenesis.
• Patients with diabetes are unable to take up glucose efficiently, and tissues then depend on fatty acids for fuel and degrade cellular proteins to provide glucogenic amino acids to glucose synthesis.
• After some hours without a meal, the liver becomes the principal source of glucose for the brain, and liver glycogen is broken down to G1P.
• There are two major types of diabetes: Type I, Insulin-dependent (IDDM), and Type II, Non-insulin dependent (NIDDM).
• Blood glucose triggers the release of insulin, which speeds up the uptake of glucose by tissues and favours the storage of fuels as glycogen and triacylglycerols.
• Dietary fats move from the intestines to muscle and fat via the lymphatic system.
• The Cori cycle is a metabolic cooperation between skeletal muscle and liver.
• After a meal, glucose, fatty acids and amino acids enter the liver, and insulin is released in response to high blood glucose to stimulate glucose uptake.
• Excess glucose is oxidised to acetyl-CoA and into fatty acids to be exported as triacylglycerol to fat and muscles.
• Excess amino acids are converted to pyruvate and acetyl-CoA, and used for lipid synthesis.
• Uncontrolled diabetes is characterised by high levels of glucose in the blood and urine and production and excretion of ketone bodies.
• During strenuous exercise, muscles use glycogen as an energy source, generating lactate via glycolysis.
• The glucose is released into the blood and returned to the muscles to replenish the glycogen stores.
• Concentration of blood glucose is hormonally regulated.
• G1P is converted to G6P, then into free glucose which is released into the blood.
• Diabetes Mellitus is a deficiency in the secretion or action of insulin.
• Amino acids from degradation of proteins and glycerol from the breakdown of triacylglycerols are used for gluconeogenesis.
• Liver continues to use fatty acids as principal fuel and excess acetyl-CoA is converted to ketone bodies to export to other tissues for fuel.
• Blood glucose triggers the release of glucagon, which stimulates glucose release from liver glycogen, shifts metabolism in liver and muscles to fatty acid oxidation to spare glucose for use by the brain, and in prolonged fasting, triacylglycerols become the principal fuel.
• Free fatty acids are activated and oxidised to yield acetyl - CoA and NADH.