MBBS Stage 1: Liver and Gluconeogenesis

Glucose Metabolism and the Liver

• Glucose is a vital metabolic fuel, essential for the body's functioning.
• The liver plays a crucial role in maintaining blood glucose homeostasis.
• Glucose is the preferred fuel source for all tissues, with some tissues having a continuous dependence on glucose.

Blood Glucose Concentration

• The normal physiological circulating glucose concentration is 3.9-6.2 mM.
• Average fasting blood glucose concentration is 4.4-5 mM for most adults.
• If blood glucose concentration drops to 2.5 or less, coma and death can result.
• If it rises for an extended period, dehydration, wasting of body tissue, and eventually death will result.

Roles of Glucose

• Glucose is a source of energy, generating 2 ATP through glycolysis and 31 ATP through oxidative phosphorylation.
• It is a source of NADPH, necessary for synthetic reactions, fatty acid synthesis, and drug metabolism.
• Glucose is a source of pentose sugars for synthetic reactions, such as nucleotide and DNA synthesis.
• It is a source of carbon for other sugars and glycoconjugates.

Advantages and Disadvantages of Glucose as a Metabolic Fuel

• Advantages: water-soluble, no carrier required in circulation, can cross the blood-brain barrier, and can be oxidized anaerobically.
• Disadvantages: relatively low yield of ATP/mole compared to fatty acids, osmotically active, and can cause direct cellular damage or accumulate toxic by-products in high concentrations.

Pathways Involving Glucose

• Predominant pathways involving glucose differ in various tissues.
• The liver can provide glucose for other tissues.
• Glucose is used in glycolysis, glycogen synthesis, and the pentose phosphate pathway in different tissues.

Role of Glucose in Different Tissues

• Skeletal muscle: glycolysis for anaerobic muscle contraction, glycolysis/TCA cycle for energy, and glycogen synthesis/degradation for energy storage.
• Heart/brain: glycolysis/TCA cycle for energy.
• Adipose tissue: glycolysis for production of glycerol phosphate for TAG synthesis.
• Erythrocyte: glycolysis for energy, pentose phosphate pathway for NADPH synthesis.

Glucose-6-Phosphate Dehydrogenase Deficiency

• X-linked hereditary disorder, affecting more than 400 million people worldwide.
• Triggers for hemolytic anemia in people with G6PD deficiency include favism, resulting from the ingestion of fava beans.

Gluconeogenesis

• Gluconeogenesis is the synthesis of glucose from non-carbohydrate sources in the liver.
• Sources: lactate, glycerol, other monosaccharides, and glucogenic amino acids (all except leu and lys).
• Not from fatty acids.
• Gluconeogenesis is not simply the reversal of glycolysis, with three irreversible reactions in glycolysis that must be bypassed.

Regulation of Gluconeogenesis

• Mobilization of substrate: glycerol from fat breakdown, amino acids from muscle protein breakdown.
• Activation of enzymes: G6Pase, F1,6bisPase, PEPCK, and pyruvate carboxylase.
• Regulation by insulin, glucagon, and adrenaline.

Blood Glucose Maintenance

• Insulin, glucagon, and adrenaline signal and coordinate the activities of the liver, adipose tissue, and muscle tissue to maintain physiological blood glucose concentrations.
• Insulin promotes synthesis and storage, while glucagon promotes degradation of stored fuel.

Insulin and Glucagon

• Insulin: anabolic hormone, promoting synthesis and storage.
• Glucagon: catabolic hormone, promoting degradation of stored fuel.
• Sites of insulin action: liver, adipose tissue, and muscle.
• Metabolic effects of insulin: inhibition of gluconeogenesis, activation of glycogen synthesis, increased fatty acid synthesis, and increased amino acid uptake and protein synthesis.

Metabolic Effects of Glucagon

• Increase in blood glucose: increase in glycogenolysis and gluconeogenesis in the liver.
• Increase in circulating fatty acids and ketone bodies: increase in adipose tissue lipolysis, fatty acid oxidation in the liver, and ketone body formation.
• Decrease in plasma amino acids: increase in uptake by the liver for gluconeogenesis.

This quiz covers the liver's role in glucose metabolism, including gluconeogenesis, glucose sources, and blood glucose homeostasis. It's a comprehensive test for MBBS Stage 1 students.