Enzymes fatty acid synthetase

The pathway from acetate to palmitic acid (actually a palmitic acid-acyl carrier protein complex) involves at least nine enzymes acetyl CoA synthetase, acetyl CoA carboxylase, and the seven enzyme fatty acid synthetase complex. We chose first to test the effect of these compounds on acetyl CoA carboxylase (ACCase) activity. There were several reasons to select ACCase as the... 

Following the administration of insulin to diabetic rats, fatty acid synthesis increases [90,100,102-104] as would be predicted, increases are observed in the citrate cleavage enzyme, fatty acid synthetase, and... 

Kater MM, Koningstein GM, Nijkamp HJJ and Stuitje AR. The use of a Hybrid Genetic System to Study the Functional Relationship between Prokaryotic and Plant Multi-Enzyme Fatty Acid Synthetase Complexes. Plant Mol Biol 1994 in press. 

We can descnbe the major elements of fatty acid biosynthesis by considering the for mation of butanoic acid from two molecules of acetyl coenzyme A The machinery responsible for accomplishing this conversion is a complex of enzymes known as fatty acid synthetase Certain portions of this complex referred to as acyl carrier protein (ACP), bear a side chain that is structurally similar to coenzyme A An important early step m fatty acid biosynthesis is the transfer of the acetyl group from a molecule of acetyl coenzyme A to the sulfhydryl group of acyl carrier protein... 

Fatty acid synthetase (Section 26 3) Complex of enzymes that catalyzes the biosynthesis of fatty acids from acetate Field effect (Section 19 6) An electronic effect in a molecule that IS transmitted from a substituent to a reaction site via the medium (e g solvent)... 

Fatty acid synthetase (Section 26.3) Complex of enzymes that catalyzes the biosynthesis of fatty acids from acetate. 

The key enzymes involved in the biosynthetic pathways of the Type I compounds are the fatty acid synthesis enzymes acetyl-CoA carboxylase and fatty acid synthetase. These enzymes are similar to those that produce the normal fatty acids used by all organisms. The resulting products are palmitic (16 car-... 

This enzyme, officially known as 3-hydroxypalmitoyl-[acyl-carrier protein] dehydratase [EC 4.2.1.61], is the fatty-acid synthase component that catalyzes the conversion of (3 i )-3-hydroxypalmitoyl-[acyl-carrier protein] to form 2-hexadecenoyl-[acyl-carrier protein] and water. This enzyme displays specificity toward 3-hydroxyacyl-[acyl-carrier protein] derivatives (with chain lengths from Ci2 to Cie), with highest activity on the palmitoyl derivative. See also Fatty Acid Synthetase... 

This enzyme [EC 2.3.1.41], also known as 3-oxoacyl-[acyl-carrier protein] synthase, catalyzes the reaction of an acyl-[acyl-carrier protein] with malonyl-[acyl-carrier protein] to produce a 3-oxoacyl-[acyl-carrier protein], carbon dioxide, and the [acyl-carrier protein]. See also Fatty Acid Synthetase... 

Smith, S. 1976. Structural and functional relationships of fatty acid synthetases from various tissues and species. In Immunochemistry of Enzymes and Their Antibodies. M.G.J. Salton, (Editor). John Wiley Sons, New York, pp. 125-146. 

L Kuhn, H Castorph, E Schweizer. Gene linkage and gene-enzyme relations in the fatty-acid-synthetase system of Saccharomyces cerevisiae. Eur J Biochem 24 492-497, 1972. 

The synthesis of several lipogenic enzymes is stimulated in the liver by thyroid hormones. For instance the concentration of acetyl Co A carboxylase, fatty acid synthetase and malic enzyme is increased in vivo after T3 injection [66-69],... 

The acetyl-CoA generated from citrate is then used for fatty acid biosynthesis. In the human being, only two multifunctional enzymes are involved acetyl-CoA carboxylase (also termed malonyl-CoA synthetase) and fatty acid synthetase, with a molecular weight of 500,000, and coded by a single gene. The product of the two enzymes is palmitate. Other fatty acids may be made from palmitate by chain unsaturation, or elongation, or both (see later). The initial reaction involves the carboxylation of acetyl-CoA in two steps by acetyl-CoA carboxylase. Biotin is a cofactor, and one molecule of ATP is hydrolyzed to ADP and Pc ... 

Figure 19.13 Biosynthesis of palmitate via fatty acid synthetase. The numbered enzyme activities (steps) are as follows (1) acetyl-CoA transacylase (2) malonyl-coA transacylase (3) /3-ketoacylsynthetase (4) j3-ketoacylreductase (5) /3-hydroxyacyldehydratase (6) enoyl reductase (7) fatty acyltransacylase. (Reproduced by permission from Wakil SJ, Stoops JK, Joshi VC. Fatty acid synthesis and its regulation. Annu Rev Biochem 52 537-579, 1983.)...

The ER elongation system works similarly to the fatty acid synthetase sequence, except that individual enzymes (gene products) are involved palmitoyl-CoA reacts with malonyl-CoA to give C02 and /3-ketooctadecanoyl-CoA. The... 

Although fatty acid 8-oxidation is catalyzed by a series of intramitochon-drial enzymes, and the fatty acyl chain is carried by CoA, fatty acid synthesis is catalyzed by a cytosolic-multienzyme complex in which the growing fatty acyl chain is bound by thioester linkage to an enzyme-bound 4 -phosphopantetheine residue. This component of the fatty acid synthetase complex is ACP. 

Figure 1.8 shows the synthesis of fatty acids. This complex process is catalysed by the multienzymatic complex, fatty acid synthetase. This enzyme uses as substrates acetyl-coA and malonyl-coA to produce palmitic acid. Afterwards, palmitic acid, a saturated fatty acid of 16 carbon atoms, can be used to produce other fatty acids (Ratledge and Evans 1989). Fatty acids with more carbon units, such as estearic acid, are obtained by elongation of palmitic acid. 

Thus, the lipid biosynthetic enzyme system evolved in extreme halophiles to utilize the (halophilic) mevalonate pathway for synthesis of virtually all of its hydrocarbon (isoprenoid/isopranoid) chains, rather than the (non-halophilic) fatty-acid synthetase system which was retained only for synthesis of normal fatty acid chains required for incorporation into proteins of the red membrane (Pugh and Kates, unpublished data). Starting from acetate and involving lysine, which provides the branch-methyl and methine carbons [88]), the mevalonate pathway proceeds to geranylgeranyl-PP (GG-PP) [13,15,89] as follows ... 

The observation that the fatty acid synthetase (FAS) in H. cutirubrum is strongly inhibited by high salt concentration while the mevalonate enzyme system for isoprenoid biosynthesis has an absolute requirement for high salt concentration (see section 4.1) may offer a clue to the mechanism of evolution of extreme halophiles from non-halophilic, or moderately halophilic precursors, and possibly also for the evolution of the methanogens and extreme thermophiles. The following hypothetical scenarios are offered for discussion (see ref [107] and Figs. 9, 14) ... 

New (de novo) fatty acids are synthesized from two-carbon acetyl units produced during metabolism. Two enzyme complexes, acetyl-coenzyme A carboxylase and fatty acid synthetase, work in concert to build up fatty acid chains, two carbons at a time, until released by the complex. The primer in plants and animals is essentially a two-carbon acetyl group and the fatty acid chains have even numbers of carbons. If the primer is a three-carbon propionate group, odd-number carbon chains result. Odd-number fatty acids are common in microbial lipids and also are synthesized de novo from propionic VFA by rumen bacteria and deposited in adipose tissue. The length of the fatty acid synthesized depends on the tissue. Palmitic acid is produced in the liver and adipose tissue, and shorter-chain fatty acids are also produced in the mammary glands (49). 

If the Fatty Acid Synthetase Complex only makes palmitate where do the rest of the fatty acids come from Of course palmitate can be shortened by P-oxidation. For longer fatty acids there is a fatty acid elongation system localized on the ER. The same reactions occur as in the S)mthetase, but now have individual enzymes. Palmitate is first activated to palmitoyl-CoA. The enzymes prefer C-16 or less as... 

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