Fatty acid synthetase degradation

A separate very long-chain-acyl-CoA synthetase is present in peroxisomes for the activation of very long-chain fatty acids, such as arachidonate (20 carbon atoms). These fatty acids are degraded exclusively in the peroxisomes. 

P-oxidation of fatty acids is a major metabolic process in which fatty acids are degraded in the mitochondria and peroxisome to produce energy [59, 60], P-oxidation occurs at the P-carbon (C-3) of the fatty acid. However, fatty acids must be activated for degradation before being P-oxidized, because negatively charged fatty acids cannot enter the plasma membrane. Activation of fatty acids are catalyzed by fatty acyl-CoA synthetase (FACS, or called thiokinases) to form fatty acyl-CoA thioester [61]. The net reaction of this activation process is ATP-dependent. 

Howard (1968b) studied fatty acid synthetic systems in cell-free preparations from squirrel monkey aortas, and the data were similar to those for the rabbit aorta with regard to the mitochondrial system. Acetate or acetyl-CoA was a more efficient precursor than malonyl-CoA, and the Schmidt degradation data indicated that it was primarily an elongation system. The cytosol or HSS was examined, and malonyl-CoA was found to be incorporated into fatty acids 55-200 times more actively than acetyl-CoA, a finding that had been noted previously in liver HSS by Abraham et al. (1962a). Majerus and Lastra (1967) noted that malonyl-CoA was incorporated into fatty acids six or seven times as fast as acetyl-CoA by human leukocytes. The latter authors were unable to find any acetyl-CoA carboxylase activity in leukocytes and reasoned that these cells possess only the fatty acid synthetase. As they pointed out, in the absence of any acetyl-CoA carboxylase, the synthetase alone uses 1 mole of acetyl-CoA plus 7 moles of malonyl-CoA to make 1 mole of palmitate (Wakil... 

Volpe, J. J., Lyles, T. O., Roucari, D. A. K., and Vagelos, P. R., 1973, Fatty acid synthetase of developing brain and liver. Content, synthesis and degradation during development, J. Biol. Chem. 248 2502. 

In the same way as the actual levels of acetyl-CoA carboxylase protein can be changed in animals under dietary influence so can that of fatty acid synthetase (Table 3.11). Up to 20-fold differences have been observed in the levels of, for example, liver fatty acid synthetase between starved and re-fed animals. Alterations in both synthesis and degradation of the enzyme seem to be involved. 

These changes in animal fatty acid synthetase (FAS) levels have now been studied at the subcellular level. FAS mRNA has been isolated from different tissues after various hormonal or dietary manipulations and translated in vitro. Recombinant plasmids have been used to ascertain the size of FAS mRNA and also the amounts of this mRNA in tissues. By these means it has been shown that differences in FAS activity are caused by changes in enzyme levels rather than its intrinsic activity. These alterations are themselves changed by the balance of enzyme synthesis and degradation, mediated by the quantity of FAS mRNA present in the cell. 

Coleman, R.A., Lewin, T.M., Van Horn, C.G., Gonzalez-Baro, M.R. 2002. Do long-chain acyl-CoA synthetases regulate fatty acid entry into synthetic versus degradative pathways . / Nutr. 132, 2123-2126. 

Many aroma compounds in fruits and plant materials are derived from lipid metabolism. Fatty acid biosynthesis and degradation and their connections with glycolysis, gluconeogenesis, TCA cycle, glyoxylate cycle and terpene metabolism have been described by Lynen (2) and Stumpf ( ). During fatty acid biosynthesis in the cytoplasm acetyl-CoA is transformed into malonyl-CoA. The de novo synthesis of palmitic acid by palmitoyl-ACP synthetase involves the sequential addition of C2-units by a series of reactions which have been well characterized. Palmitoyl-ACP is transformed into stearoyl-ACP and oleoyl-CoA in chloroplasts and plastides. During B-oxi-dation in mitochondria and microsomes the fatty acids are bound to CoASH. The B-oxidation pathway shows a similar reaction sequence compared to that of de novo synthesis. B-Oxidation and de novo synthesis possess differences in activation, coenzymes, enzymes and the intermediates (SM+)-3-hydroxyacyl-S-CoA (B-oxidation) and (R)-(-)-3-hydroxyacyl-ACP (de novo synthesis). The key enzyme for de novo synthesis (acetyl-CoA carboxylase) is inhibited by palmitoyl-S-CoA and plays an important role in fatty acid metabolism. 

Each plant cell manufactures its own fatty acids, since there is no lipid transport in plants. The synthesis begins with acetate which is formed from pyruvate, formed from phosphoglycerate in the Calvin cycle in leaf tissue or via degradation of sugars in seeds or fruits. De novo synthesis of fatty acids takes place in the chloroplasts of vegetative tissues or in plastids of other plant tissues. Acetate is first esterified to the -SH function of coenzyme A (CoA) via an enzyme, acetyl CoA synthetase. Coenzyme A is an adenosine derivative attached to a 4 -phosphopantetheine moiety, a chemical subunit idilch is ubiquitous in the metabolism of fatty acids. 

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