Long-chain acyl-CoA synthetases

N-Acetyl ACSL1 Acyl-CoA synthetase long-chain family member 1 4q35... 

Fatty acid transport protein paralogues 1-6 FATP 1-6 Gene symbols SLC27A1-6 Solute carrier family 27A Very long-chain acyl-CoA synthetase VLCS... 

Venus Flytrap Module Very Long-chain Acyl-CoA Synthetase Very Low-density Lipoprotein Vesicle... 

Herrmann, T., et al. Mouse fatty acid transport protein 4 (FATP4) characterization of the gene and functional assessment as a very long chain acyl-CoA synthetase. Gene 2001, 270,... 

Long-chain fatty acids must be activated and transported into the mitochondria. Fatty acyl CoA synthetase, on the outer mitochondrial membrane, activates the fatty adds by attaching CoA. The fetty acyl portion is then transferred onto carnitine by carnitine aqdtransferase-I for transport into the mitochondria. The sequence of events is shown in Figure 1-16-2 and indudes the following steps ... 

Medium-chain acyl-CoA synthetase, which is present within the mitochondrial matrix of the liver, activates fatty acids containing from four to ten carbon atoms. Medium-chain length fatty acids are obtained mainly from triacylglycerols in dairy products. However, unlike long-chain fatty acids, they are not esterified in the epithelial cells of the intestine but enter the hepatic portal vein as fatty acids to be transported to the liver. Within the liver, they enter the mitochondria directly, where they are converted to acyl-CoA, which can be fully oxidised and/or converted into ketone bodies. The latter are released and can be taken up and oxidised by tissues. 

Long-chain acyl-CoA synthetase activates fatty acids containing from 10 to 18 carbon atoms. 

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. 

This enzyme [EC 6.2.1.15], also known as arachido-nateiCoA ligase, catalyzes the reaction of arachidonate with ATP and coenzyme A to generate arachidonyl-CoA, AMP, and pyrophosphate (or, diphosphate). The enzyme can also use 8,11,14-icosatrienoate as a substrate, but not the other long-chain fatty acids. It should be noted that this enzyme is not identical to long-chain acyl-CoA synthetase [EC 6.2.1.3]. 

LEUCYL-tRNA SYNTHETASE LONG-CHAIN FATTY ACYL-CoA SYNTHETASE LUCIEERASE... 

After a LCFA enters a cell, it is converted to the CoA derivative by long-chain fatty acyl CoA synthetase (thiokinase) in the cytosol (see p. 174). Because 0-oxidation occurs in the mitochondrial matrix, the fatty acid must be transported across the mitochon drial inner membrane. Therefore, a specialized carrier transports the long-chain acyl group from the cytosol into the mitochondrial matrix. This carrier is carnitine, and the transport process is called the carnitine shuttle (Figure 16.16). 

H Tomoda, K Igarashi, JC Cyong, S Omura. Evidence for an essential role of long chain acyl-CoA synthetase in animal cell proliferation. Inhibition of long chain acyl-CoA synthetase by triacsins caused inhibition ofRaji cell proliferation. JBiol Chem 266 4214-4219, 1991. 

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. 

Fatty acids of widely differing chain length can be activated, there being three acyl-CoA synthetase enzymes. One activates acetate (C2), propionate (C3), and butyrate (C4) a second activates medium-chain-length fatty acids (C4-CJ2) a third activates long- and medium-chain-length fatty acids. The long-chain acyl-CoA synthetase occurs in the mitochondria and endoplasmic reticulum and is widespread in mammalian tissues. 

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