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Endocrine, Metabolism & Exercise 2008b(12): Detail the protective and regulatory roles of the liver. General: the liver is the largest gland in the body and has multiple functions involved in many essential processes in the body. It is the interface between the gut and the body and therefore has a role in protection from organisms and toxins and regulation of nutrient levels. Protective: - involved in removal of bacteria, endotoxins and protein denaturation - these actions are primarily undertaken by Kupffer Cells located in the hepatic sinusoids - the actions of these macrophages are an example of innate immunity - Kupffer Cell activitation initiates a chain of events: o phagocytosis → complement activation → recruitment of other cells - can function as a blood reservoir: o 450mL in the liver at resting state o can ↑ to 1500mL in fluid overload o ↓intravascular volume → able to mobilize 350mL - production of acute phase proteins - drug biotransformation: o phase I: oxidation (enzyme systems eg CYP450) → unmask conjugation sites o phase II: conjugation to ↑solubility for excretion Regulatory: - primarily acts as a glucostat - metabolic roles are hormonally influenced o catabolic hormones: glucagons, cortisol, adrenaline o anabolic hormones: insulin, GH - anabolic functions o CHO: glycogenesis ↑glucose trapping (hepatocytes) 2° ↑glucokinase activity o fats: fatty acid formation • once maximal glycogen stores → glucose metabolized to pyruvate → AcetylCoA → fatty acid cholesterol/phospholipids formation o proteins: lipoproteins synthesis - catabolic functions: o CHO: glycogenolysis, gluconeogenesis (via acetyl CoA formation from fatty acid breakdown) → maintain BSL o fats: ↑lipolysis ketone body formation bile acid formation (for fat absorption) o proteins: ammonium formation (via glutathione synthesis for transport to PCT in kidney) By Michael Wirth Endocrine, Metabolism & Exercise urea: by product amino acid metabolism → ↑concentrating ability of kidney regulating production of albumin to control plasma oncotic pressure production of bile in regulating fat and fat soluble vitamin absorption bilirubin metabolism hormone inactivation production of both coagulant and anti-coagulant proteins involved in the storage of: o amino acids o iron (as ferritin) o glycogen o lipid soluble vitamins (A, D, E, K) o copper - By Michael Wirth