Macronutrient Metabolism

Carbohydrates The liver is responsible for maintaining normal blood glucose concentrations under various metabolic conditions. Among the several metabolic processes that allow this fine regulation are glycogenesis, gluconeogenesis, and glycolysis. The end product of carbohydrate digestion is 80% glucose, with the remaining 20% being fructose and galactose; the latter two are quickly converted into glucose in the liver. Once transported into the hepa-tocyte, the glucose molecule is phosphorylated (via glucokinase) and cannot leave the cell unless dephos-phorylated with glucose phosphatase. Glucose is either used for immediate energy release or stored as glycogen.

Proteins The liver plays a major role in protein metabolism in the deamination of amino acids, urea formation for removal of ammonia, plasma protein synthesis, and in the interconversions among amino acids. Ingested protein is the sole source of the 10 essential amino acids and the primary source of nitrogen necessary for the synthesis of other amino acids. Protein is digested and broken down to amino acids that are absorbed into the circulation and taken to cells throughout the body, primarily the liver, and quickly become combined by peptide linkages. The plasma level of amino acids is tightly controlled and maintained near a constant level. Once the cellular limit of protein storage is met, excess amino acids are degraded and used for energy or stored as fat or glycogen. The liver is the primary site of all amino acid catabolism with the exception of branch-chained amino acid catabolism, which occurs in the muscle cells. The urea cycle, in which the toxic compound ammonia is converted to urea, occurs solely in the liver. The synthesis of the plasma proteins albumin, fibrinogen, and globulin also occurs in the liver.

Lipids The liver plays a role in fat metabolism in four key processes: fatty acid oxidation for energy, lipoprotein syntheses, the synthesis of cholesterol and phospholipids, and the conversion of carbohydrate to fat for storage. Digested fat is a major source of energy in which after splitting into fatty acids and glycerol, the fatty acid components further split via beta oxidation into acetyl-CoA. Two molecules of acetyl-CoA become paired together to form acetoacetic acid and are transported to other cells to provide energy in the citric acid cycle.

Fat-soluble vitamins The liver plays a key role in the absorption of the fat-soluble vitamins—A, D, E, and K—as they are only successfully absorbed in association with fat and sufficient quantities of bile salts. The liver is also the primary storage site for several vitamins, including A, E, K, and B12. Vitamin A is stored in the largest quantity in a sufficient amount to prevent deficiency for 5-10 months. Vitamin D is stored in amounts sufficient for 24 months. Vitamin B12 is stored in amounts sufficient for at least 1 year. The liver is responsible for the hydroxylation of vitamin D to its storage form, 25-hydroxy vitamin D. It is released into circulation and thence delivered to the kidney where it is converted to its active form, 1, 25-dihydroxy vitamin D.

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