Fatty acid synthetase activation

Sohby, C. (1979). Regulation of fatty acid synthetase activity.. Biol. Chem. 254,8561-8566. TahiRani, A. G, and Neely,). R. (1987). A transport system for coenzyme A in isolated heart mitochondria. /. Biot. Otm. 262, 11607-11610,... 

Sohby, C. (1979). Regulation of fatty acid synthetase activity. J. Biol. Chem. 254, 8561-8566. 

Oku H, Wongtangtintham S, Iwasaki H, Toda T. (2003) Conjugated linoleic acid (CLA) inhibits fatty acid synthetase activity in vitro. Biosci Biotechnol Biochem 67 1584-1586. 

Insulin deficiency impairs several steps in lipogenesis as a result of decreased penetration of glucose and utilization in glycolytic pathway with reduced formation of a-glycerophosphate, decreased pyruvate dehydrogenase and acetyl CoA carboxylase activities with reduced fatty acid chain initiation, decreased fatty acid synthetase activity. 

Gellhorn and Benjamin (1966) have demonstrated that oxidative desaturation of saturated fatty acids becomes depressed in the diabetic state and that this enzymatic impairment is reversed by insulin. Since insulin can also reverse the diabetic depressed llpogenlc activity, it is fair to assume that the insulin-Induced rise in hepatic desaturase activity could be mediated by the increase in de novo fatty acid synthesis. Mercurl et al. (1974) demonstrated that dietary fructose or glycerol was able to partially restore the A9 desaturase activity depressed by the diabetic state. Since utilization of these carbohydrates by the liver is not insulin dependent (Takeda et al , 1967 and Howard and Lowenstein, 1967) and the fatty acid synthetase activity is increased by a fructose or glycerol supplemented diet (Volpe and Vagelos, 1974 and Bruckdorfer et al., 1972), further research in this area may increase our understanding of these metabolic relationships. 

Figure 1. Incorporation of 10 0 Figure 2. Incorporation of 18 1 and 12 0 into triacylglycerols (A) (A) and 18 2 (A) into triacyl-Free fatty acids ( ). Acyl-CoA glycerols. Free fatty acids ( ). synthetase activity (B). Acyl-Coa synthetase activity (B).

DAG feeding reduces fatty acid synthetase activity and elevates the activities of enzymes involved in P-oxidation in the liver of rats. 

M. L. Ernst-Fonberg, Fatty acid synthetase activity in Euglena gracelis variety bacillarius. Characterisation of an acyl carrier protein dependent system. Biochemistry 12 2 9 (1973). 

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... 

Knudsen and Grunnet (1982) have proposed an interesting system for the control of medium-chain fatty acid synthesis by ruminant mammary tissue. Their proposal is based on their observations that ruminant mammary tissue fatty acid-synthetase exhibits both medium-chain thioesterase (Grunnet and Knudsen 1978) and transacylase (Knudsen and Grunnet 1980) activity and that medium-chain fatty acids synthesized de novo can be incorporated into TG without an intermediate activation step (Grunnet and Knudsen 1981). They proposed that the synthesis of the medium-chain fatty acids is controlled by their incorporation into TG (Grunnet and Knudsen 1981). Further work will be needed to substantiate transacylation as a chain-termination mechanism in fatty acid synthesis by ruminant mammary tissue. 

Grunnet, I. and Knudsen, J. 1978. Medium chain acyl-thioester hydrolase activity in goat and rabbit mammary fatty acid synthetase complexes. Biochem. Biophys. Res. Commun. 80, 745-749. 

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.)...

Fatty acid synthetase has all the activities that would be necessary to reverse the /8-oxidation pathway. Thus, a cis double bond is generated from /3-hydroxy fatty acyl-CoA residues by a dehydration process. 

Grunnet, I., Knudsen, J. 1981. Direct transfer of fatty acids synthesized de novo from fatty acid synthetase into triacylglycerols without activation. Biochem. Biophys. Res. Com. 100, 629-636. 

Each of the enzymatic activities located in a single polypeptide chain of the mammalian fatty acid synthetase exists as a distinct protein in E. coli. The acyl-carrier protein (ACP) of E. coli has an Mr = 8,847 and contains 4-phosphopantotheine. The dehydratase has a molecular weight of 28,000 and catalyzes either trans 2-3 or cis 3-4 dehydration of the hydroxy acid intermediates in the biosynthesis of palmitic acid. When the chain length of the hydroxy fatty acid is C[ the synthesis of palmitoleic acid is achieved as follows ... 

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... 

When cells of H. cutirubrum were grown in the presence of [ C]acetate, over 98% of the label was incorporated into the isopranyl (phytanyl) groups of the polar lipids, and less than 0.5% was found in long-chain fatty acids [86]. Cell-free studies subsequently demonstrated the presence of a fatty acid synthetase (FAS) which is largely ( 80%) inhibited by 4M NaCl or KC1[87]. However, sufficient FAS activity remains for the formation of saturated fatty acids (14 0, 16 0, 18 0) recently found to be esterified to proteins of the red membrane but not to bacteriorhodopsin in the purple membrane of extreme halophiles nor to the polar lipids (Pugh and Kates, unpublished data). 

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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