Liver carbohydrate metabolism

Soengas, J.L., Barciela, P., Fuentes, J., Otero, J., Andrds, MD. and Aldegunde, M. (1993). The effect of seawater transfer on liver carbohydrate metabolism of domesticated rainbow trout (Oncorhynchus mykiss). Comparative Biochemistry and Physiology 105B, 337-343. 

Weber, G., Lea, M. A., and Stamm, N. B., 1968, Sequential feedback inhibition and regulation of liver carbohydrate metabolism through control of enzyme activity, Adv. Enzyme Regul. 6 101. 

The fatty acids released on triacylglycerol hydrolysis are transported to mitochondria and degraded to acetyl CoA, while the glycerol is carried to the liver for further metabolism. In the liver, glycerol is first phosphorylated by reaction with ATP. Oxidation by NAD+ then yields dihydroxyacetone phosphate (DHAP), which enters the carbohydrate metabolic pathway. We ll discuss this carbohydrate pathway in more detail in Section 29.5. 

Isotopes were not available in van t Hoff s day. My student generation was taught that an asymmetric carbon atom was a carbon atom attached to 4 chemically different groups. When isotopes of carbon, UC and 13C, were first applied as tracers to study carbohydrate metabolism, the entire emphasis was on the chemical similarity of 11C and 13C to the more abundant isotope 12C. Thus, it was of pressing interest to determine whether CO 2 participated in the oxidation of carbohydrate in animal tissues, a conclusion strongly suggested by the demonstration in Krebs laboratory, that pyruvate and oxalacetate behaved alike in pigeon liver, and by Wood and Werkman s earlier demonstration that some he-... 

Because of its involvement with many aspects of lipid metabolism so far described, it will be apparent from the discussion so far that acetyl-CoA is an axle around which hepatic lipid metabolism revolves. Indeed, acetyl-CoA links lipid and carbohydrate metabolism. Figure 6.20 summarizes the central role of acetyl-CoA in lipid related pathways in the liver. 

The calorific capacity of amino acids is comparable to that of carbohydrates so despite their prime importance in maintaining structural integrity of cells as proteins, amino acids may be used as fuels especially during times when carbohydrate metabolism is compromised, for example, starvation or prolonged vigorous exercise. Muscle and liver are particularly important in the metabolism of amino acids as both have transaminase enzymes (see Figures 6.2 and 6.3 and Section 6.4.2) which convert the carbon skeletons of several different amino acids into intermediates of glycolysis (e.g. pyruvate) or the TCA cycle (e.g. oxaloacetate). Not all amino acids are catabolized to the same extent... 

There are data from animal studies in mice, rats, and pigs that indicate that both carbohydrate metabolism and lipid metabolism may be affected by exposure to heptachlor or heptachlor epoxide (Enan et al. 1982 Halacka et al. 1974 Kacew and Singhal 1973 Pelikan 1971). Alterations in gluconeogenic enzymes and an increase in cellular steatosis in the liver have been reported. Granulomas and fibrotic liver have also been observed. In addition, hepatocellular carcinoma was identified as causally related to heptachlor in the diet in a mouse study conducted by the National Cancer Institute (NCI 1977). The existing evidence suggests that heptachlor and heptachlor epoxide are hepatic toxicants. 

In all organisms, carbohydrate metabolism is subject to complex regulatory mechanisms involving hormones, metabolites, and coenzymes. The scheme shown here (still a simplified one) applies to the liver, which has central functions in carbohydrate metabolism (see p. 306). Some of the control mechanisms shown here are not effective in other tissues. 

The effects of insulin on carbohydrate metabolism are discussed on p. 158. In simplified terms, they can be described as stimulation of glucose utilization and inhibition of gluconeogenesis. In addition, the transport of glucose from the blood into most tissues is also insulin-dependent (exceptions to this include the liver, CNS, and erythrocytes). 

Carbohydrate metabolism. The liver takes up glucose and other monosaccharides from the plasma. Glucose is then either stored in... 

The signal is often modulated by integration with input from other signaling pathways (eg, the insulin/glucagon ratio is important for balancing carbohydrate metabolism in the liver). 

Mechanism of Action Acts as a coenzyme for various metabolic functions, including fat and carbohydrate metabolism and protein synthesis. Therapeutic Effect Necessary for cell growth and replication, hematopoiesis, and myelin synthesis. Pharmacokinetics In the presence of calcium, absorbed systemically in lower half of ileum. Initially, bound to intrinsicfactor this complex passes down intestine, binding to receptor sites on ileal mucosa. Protein binding High, Metabolized in the liver. Primarily eliminated unchanged in urine. Half-life 6 days. 

Mecfianism of Action A cinchona alkaloid that relaxes skeletal muscle by increasing the refractory period, decreasing excitability of motor end plates (curare-like), and affecting distribution of calcium with muscle fiber. Antimalaria Depresses oxygen uptake, carbohydrate metabolism, elevates pH in intracellular organelles of parasites. Therapeutic Effect Relaxes skeletal muscle produces parasite death. Pharmacokinetics Rapidly absorbed mainly from upper small intestine. Protein binding 70%-95%. Metabolized in liver. Excreted in feces, saliva, and urine. Half-life 8-14 hr (adults), 6-12 hr (children). 

FIGURE 15-32 Difference in the regulation of carbohydrate metabolism in liver and muscle. In... 

To meet these changing circumstances, the liver has remarkable metabolic flexibility. For example, when the diet is rich in protein, hepatocytes supply themselves with high levels of enzymes for amino acid catabolism and gluconeogenesis. Within hours after a shift to a high-carbohydrate diet, the levels of these enzymes begin to drop and the hepatocytes increase their synthesis of enzymes essential to carbohydrate metabolism and fat synthesis. Liver enzymes turn over (are synthesized and degraded) at live to ten times the rate of enzyme turnover in other tissues, such as muscle. Extrahepatic... 

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