Fatty add synthase

FIGURE 25.9 Fatty add synthase in animals contains all the functional groups and enzyme activities on a single multifunctional subunit. The active enzyme Is a head-to-tall dimer of Identical subunits. (Adapted from Wakit, S. J., Stoops,... 

Fatty add synthase is a large multienzyme complex in the cytoplasm that is rapidly induced in the liver after a meal by high carbohydrate and the concomitant rise in insulin levels. It contains an acyl carrier protein (AGP) that requires the vitamin pantothenic add. Althoi malonyl CoA is the substrate used by fetty acid synthase, only the carbons from the acetyl CoA portion are actually incorporated into the fatty acid produced. Therefore, the fetty add is derived entirely from acetyl CoA. 

In the vertebrates, biosynthesis of fatty acids is catalyzed by fatty add synthase, a multifunctional enzyme. Located in the cytoplasm, the enzyme requires acetyl CoA as a starter molecule. In a cyclic reaction, the acetyl residue is elongated by one C2 unit at a time for seven cycles. NADPH+H is used as a reducing agent in the process. The end product of the reaction is the saturated Cie acid, palmitic acid. 

This enzyme [EC 2.3.1.38], also referred to as acetyl-CoA [acyl-carrier protein] 5-acetyltransferase, transfers an acetyl group from one acetyl-CoA to an acyl-carrier-protein (ACP) to form free coenzyme A and the acetyl-[acyl-carrier-protein]. See also Fatty Add Synthase... 

Seven rounds of reactions occur on fatty add synthase to synthesize one molecule of palmitic acid. 

The serum level of pantothenic add is about 1 to 5 lM (Lopaschuk d ai, 1987). The vitamin in the bloodstream is transported into various tissues, where it is then converted to coenzyme A. Coenzyme A is synthesized from pantothenic add, ATP, and cysteine. The pathway of coenzyme A synthesis is shown in Figure 9,77. The cofactor of fatty add synthase is synthesized from coenzyme A and does not involve the direct participation of pantothenic acid. A specific enzyme catalyzes... 

Covniyme A 3, 5 -Ad4no)ine diptwaphstv FtGURl 9.7S Conversion of fatty add synthase to the holoenzyme form. 

It is unclear how the synthesis of predominantly short-chain fatty acids occurs, especially as the fatty acid synthase from the uropygial gland appears to have the same characteristics as in other tissues. During the biosynthesis of fatty acids from malonyl-CoA and methylmalonyl-CoA by the fatty add synthase, the growing chain is attached to the pantotheine group of the multienzyme polypeptide by a thioester link. One of the enzyme activities associated with a domain of the multienzyme polypeptide is the thioesterase (reaction 4.4), which has a specificity for cleaving thioesters of longer chain fatty acids esterified to the acyl carrier protein (ACP). 

Fischer, P.W.F. Goodridge, A.G. (1978). Coordinate regulation of acetylCoA carboxylase and fatty add synthase in liver cells of the developing chick in vivo and in culture. Arch. Biophys. Biochem., 190, 332—44. 

Foster, R.J., Bonsall, R.F., Poulose, A.J. Kolattukudy, P.E. (1985). Interaction of S-acyl fatty add synthase thioester hydrolase with fatty add synthase. ]. Biol Chem., 260, 1386-9. 

E., and Wilmer,. (2006) Plant cyclopropane fatty add synthase genes and uses thereof WO/2005/087354. 

Type II fatty add synthase. 6-7 discrete enzymes and an acyl carrier protein, assodated noncovalently. In plants the enzymes are only in the plastids, and fatty add synthesis does not occur in the cytoplasm. Similarity of plant and bacterial type II systems supports endosymbiont theory of origin of chloro-plasts. Enoyl reductase uses FMN. Primary product is palmitate. 

The Aflatoxin Polyketide Synthase/Fatty Add Synthase Complex... 

An inhibition of one of the enzymes involved in fatty add synthesis is consistent with retarded lipogenesis. The enzyme considered to be rate-limiting in fatty add synthesis, i.e. acetyl-CoA carboxylase, and another fatty add synthesis enzyme, i.e. fatty add synthase, are both downregulated by hypolipidaemic EPA-derivatives. Thus, the hypolipidaemic effect observed by administration of the EPA-derivatives to rats could be due to both increased fatty acid oxidation and reduced lipogenesis. However, other results by our group indicate that the fatty acid oxidation is the major cause of the hypolipidaemic effect. 

T. Maier, S. Jenni, N. Ban, Aichitectuie of mammeilian fatty add synthase at 4.5 angstrom... 

Hauvermale, A., Runer, J., Rosenzweig, B., Guerra, D., Diltz, S and Metz, J.G. (2006) Fatty acid production in Schizochytrium sp. involvement of a polyunsaturated fatty acid synthase and a Type I fatty add synthase. Lipids, 41, 739-747. 

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