Medium-chain acyl-CoA synthetase

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. 

Oka Y, Kobayakawa K, Nishizumi H, Miyamichi K, Hirose S, Tsuboi A, Sakano H (2003) O-MACS, a novel member of the medium-chain acyl-CoA synthetase family, specifically expressed in the olfactory epithelium in a zone-specific manner. Eur J Biochem 270(9) 1995-2004 Potter SM, Zheng C, Koos DS, Feinstein P, Fraser SE, Mombaerts P (2001) Structure and emergence of specific olfactory glomeruli in the mouse.J Neurosci 21(24) 9713-9723 Ray A, van Naters WG, Shiraiwa T, Carlson JR (2007) Mechanisms of odor receptor gene choice in Drosophila. Neuron 53(3) 353-369... 

EC 6.2.1.1 Short-chain fatty acyl-CoA synthetase (ACSS) EC 6.2.1.2 Medium-chain acyl-CoA synthetase EC 6.2.1.3 Long-chain acyl-CoA synthetase [ACSL)... 

Kasuya, E, Igarashi, K., Fukui, M. Participation of a medium chain acyl-CoA synthetase in glycine conjugation of the benzoic acid derivatives with the electron-donating groups. Biochem. Pharmacol. 1996, 51, 805-809. 

Medium-chain acyl-CoA synthetases exist in mitochondria of various mammalian tissues. The enzyme present in heart mitochondria acts on fatty acids with three to seven carbon atoms, but is most active with butyrate. In contrast, a 62-kDa enzyme of liver mitochondria activates fatty acids with 4-14 carbon atoms with octanoate being the best substrate. This enzyme also activates aromatic carboxylic acids such as benzoic acid and... 

Short-chain and medium-chain fatty acids with less than 10 carbon atoms can enter mitochondria as free acids independent of carnitine. They are activated by short-chain and medium-chain acyl-CoA synthetases that are present in the mitochondrial matrix. 

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. 

Other genes involved in mitochondrial lipid metabolism, such as acyl-CoA synthetase" or medium-chain acyl-CoA dehydrogenase (MCAD), are also targets of PPAR, indicating that different steps of fatty acid metabolism, like activation, oxidation, and utilization of fatty acids are regulated by the levels of the substrate, the fatty acids. Therefore, we speculated that the main control step in fatty acid P-oxidation, the outer membrane component of carnitine palmitoyltransferase enzyme system, CPT 1, could also be a PPAR target. 

Both reactions are freely reversible but the overall reaction is driven to the right by pyrophosphatase activity and/or by the re-phosphorylation of AMP. The short chain acyl-AMP is thought to be enzyme-bound. In the medium and long chain acyl-CoA synthetases, however, acyl-AMP is probably only formed as a side-product or with unphysiological or conformationally changed enzyme forms. This would explain why intermediary enzyme complexes were formed when medium and long chain synthetases were incubated with ATP and medium and long chain fatty acids but that acetyl-AMP could not be identified when the short chain synthetase was incubated with acetate. 

ACSM1 Acyl-CoA synthetase medium-chain family member 1 16pl2.3... 

The acyl CoA synthetase that activates long-chain fatty acids, 12 to 20 carbons in length, is present in three locations in the cell the endoplasmic reticulum, outer mitochondrial membranes, and peroxisomal membranes (Table 23.1). This enzyme has no activity toward C22 or longer fatty acids, and little activity below C12. In contrast, the synthetase for activation of very-long-chain fatty acids is present in peroxisomes, and the medium-chain-length fatty acid activating enzyme is present only in the mitochondrial matrix of liver and kidney cells. 

Figures 1 and 2 show the capacity of insect homogenates from various stages of development to incorporate medium chain fatty acids (10 0 and 12 0) (fig. lA) as well as unsaturated 18C (18 1 and 18 2) (fig. 2A). In all cases a crossing-zone between the radioactivity patterns of free fatty acids and triacylglycerols is defined in clear coincidence with the larval-pupal apolysis stage. This metabolic difference between larval and pharate adult homogenates could not be explained through differences in the acyl-CoA synthetase activity of the insect furthermore,the enzyme activity increases notably from the larval to the adult stage of development in a manner similar for each fatty acids (figs. IB and 2B).

Fatty acyl-CoA synthetase. Cytosolic processing of fatty acid and lipid formation is a highly integrated process. An active acyl-CoA pool exists and is dependent upon a supply of fatty acid from the plastid. The composition of this pool can be analyzed by capillary electrophoresis (MacKenzie and Taylor, 1990). Formation of acyl-CoAs involves fatty acyl-CoA synthetase (EC 6.2.1.3) and appears to occur on the inner face of the plastidic envelope. While a broad specificity for fatty acids exists in various oilseeds, a preference is shown for medium-chain fatty acids in Cuphea and for very-long-chain fatty acids in Crambe (Battey and... 

The synthesis of fatty acids for incorporation into milk fat within the mammary gland is similar to that seen in other tissues. There are two basic reactions the conversion of acetyl-coenzyme A (CoA) to malonyl-CoA, followed by incorporation of the latter into a growing acyl chain via the action of the fatty acid-synthetase complex. However, the product of these reactions in lactating mammary tissue from many species is short and medium chain fatty acids. In most other tissues the product is palmitate. For more complete details see Moore and Christie, (1978), Bauman and Davis (1974), and Patton and Jensen (1976). 

Knudsen, J., Grunnet, I. 1982. Transacylation as a chain-termination mechanism in fatty acid synthesis by mammalian fatty acid synthetase. Synthesis of medium-chain-length (Cg — C12) acyl-CoA esters by goat mammary gland fatty acid synthetase. Biochem J. 202, 139-143. 

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