Hepatic fatty acid synthase

Ren, B., Thelen, A. P., Peters, J. M., Gonzalez, F. J., and Jump, D. B. Polyunsaturated fatty acid suppression of hepatic fatty acid synthase and S14 gene expression does not require peroxisome proliferator-activated receptor alpha. J Biol Chem 272 (1997) 26827-26832. 

Fatty acid synthase inhibition. Petroleum ether extract of the fresh fruit, administered to pigs at a concentration of 3.5 g/kg of diet for 29 days, was active on hepatic enzymes l... 

Nakamura MT, Cho HP, Clarke SD. Regulation of hepatic delta-6 desaturase expression and its role in the polyunsaturated fatty acid inhibition of fatty acid synthase gene expression in mice. J Nutr 2000 30 1561-1565. 

Fig. 3. Effects of c9,f11 -conjugated linoleic acid (CLA) and f10,c12-CLA on hepatic carnitine palmitoyltransferase (CPT) and fatty acid synthase (FAS) activities in OLETF rats. Rats were fed control diet (LA) or CLA diets (1 % c9,f11-CLA or flO,cl 2-CLA) for 2 wk. Values with different letters are significantly different, P< 0.05.

TTA is a fatty acid analogue in which a sulfur atom replaces the P-mehylene groups in the alkyl-chain (a 3-thia fatty acid). TTA, therefore, cannot be P-oxidized. Paradoxically, TTA is both mitochondrial and peroxisomal proliferator and the hepatic mitochondrial and peroxisomal fatty acid oxidation capacities are increased (Table 2). In addition to its biochemical and morphological effects, TTA decrease serum TG (Table 1) very low density lipoprotein (VLDL)-TG, cholesterol and free fatty acid (NEFA) levels in rats. Thus, the observed reduction in plasma TG levels during TTA administration could be accomplished by retarded synthesis, reduced hepatic output, enhanced clearance or a combination of these factors. 3-Thia fatty acid resulted in a slight inhibition in the activities of ATP-citrate lyase and fatty acid synthase. However, the impact of... 

The ketone bodies (acetoacetate, 3-hydroxybutyrate, and acetone) are formed in hepatic mitochondria when there is a high rate of fatty acid oxidation. The pathway of ketogenesis involves synthesis and breakdown of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) by two key enzymes, HMG-CoA synthase and HMG-GoA lyase. 

Rapid p-oxidation of fatty acids in perfused liver (DeBeer et a/., 1974) and in isolated mitochondria (Lopes-Cardozo and Van den Bergh, 1972) has been shown to suppress the operation of citric acid cycle apparently from the elevation of mitochondrial NADH/NAD ratio which restricts oxaloaceta-te availability for citrate synthase and simultaneously inhibits isocitrate oxidation (Lenartowicz et a/., 1976). Considerable support for an earlier postulate that oxaloacetate availability normally determines the rate of citrate synthesis has become available. Thus, because of marked protein binding, the concentration of free, as opposed to total, oxaloacetate in matrix of liver mitochondria is now estimated to be near the of citrate synthase (Siess et al., 1976 Brocks eta ., 1980). The antiketogenic effect of alanine (Nosadini et a/., 1980) and of 3-mercaptopicolinate, an inhibitor of phosphoenolpy-ruvate carboxykinase (Blackshear et a/., 1975), is believed to be exerted, at least in part, from their ability to raise hepatic oxaloacetate concentration. And, in pyruvate carboxylase deficiency, expected to impair oxaloacetate supply, concentration of ketone bodies is elevated (Saudubray et a/., 1976). 

One of the functions of hepatic P-oxidation is to provide ketone bodies, acetoac-etate and P-hydroxybutyrate, to the peripheral circulatioa These can then be utilized by peripheral tissues such as brain and heart. Beta-oxidation itself produces acetyl-CoA which then has three possible fates entry to the Krebs cycle via citrate synthase keto-genesis or transesterification to acetyl-carnitine by the action of carnitine acetyltrans-ferase (CAT). Intramitochondrial acetyl-carnitine then equilibrates with plasma via the carnitine acyl-camitine translocase and presumably via the plasma membrane carnitine transporter. Human studies have shown that acetyl-carnitine may provide up to 5% of the circulating carbon product from fatty acids and can be takem and utilized by muscle and possibly brain. In addition, acyl-camitines are of important with regard to the diagnosis of inborn errors of P-oxidation. For these reasons, we wished to examine the production of acetyl-carnitine and other acyl-camitine esters by neonatal rat hepatocytes. 

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