Acyl-CoA transferase

Saz, H.J., deBruyn, B. and de Mata, Z. (1996) Acyl-CoA transferase activities in homogenates of Fasciola hepatica adults. Journal of Parasitology 82, 694-696. 

It is likely that pyruvate, the product of the oxidative branch of the mitochondrial dismutation reaction, is further metabolised in cestodes to acetyl-CoA by oxidation with NAD+, as catalysed by the lipoamide-dependent mitochondrial pyruvate dehydrogenase complex. This enzyme has been reported in H. diminuta (935) and S. solidus (406). The acetyl-CoA is then hydrolysed to acetate. During this step, ATP synthesis may occur through the conservation of the acetyl-CoA energy-rich thioester bond by the combined action of an acyl-CoA transferase and a thiokinase (398) as follows ... 

An acyl-CoA transferase has been detected in sonicated mitochondrial preparations from Spirometra mansonoides (643). 

The synthesis of triacylglycerol takes place in the endoplasmic reticulum (ER). In liver and adipose tissue, fatty adds in the cytosol obtained from the diet or from de novo synthesis of palmitic add become inserted into the ER membrane. The reactions are shown in Fig. 13-10. Membrane-bound acyl-CoA synthetase activates two fatty acids, and membrane-bound acyl-CoA transferase esterifies them with glycerol 3-phosphate, to form phosphatidic acid. Phosphatidic acid phosphatase releases phosphate, and in the membrane, 1,2-diacylglycerol is esterified with a third molecule of fatty acid. 

Note that the enzymes CDP-choline 1,2-diacylglycerol transferase in phospholipid synthesis and acyl-CoA transferase in triglyceride synthesis have the common substrate 1,2-diacylglycerol thus we have this two-way synthesis shown in Fig. 13-13. 

A typical research example includes the synthesis of a K -channel blocker intermediate (Fig. 7.10). Here, an aminotransferase is used to replace a keto group by an amino function to yield the desired intermediate [20]. Other potential applications include the biosynthesis of flavouring esters. In nature such compoimds are often formed by a specific acyl CoA transferase. For practical purposes, however, the alternative, less complicated route, using lipases and esterases in their synthetic mode, seems more appropriate. 

FIG. 4.2 Malate metabolism in mitochondria from body wall muscle of adult Ascaris smm. (1) Fumarase (2) malic enzyme (3) pyruvate dehydrogenase complex (4) complex I (5) succinate-coenzyme Q reductase (complex II, fumarate reductase) (6) acyl CoA transferase (7) methylmalonyl CoA mutase (8) methyl-malonyl CoA decarboxylase (9) propionyl CoA condensing enzyme (10) 2-methyl acetoacetyl CoA reductase (11) 2-methyl-3-oxo-acyl CoA hydratase (12) electron-transfer flavoprotein (13) 2-methyl branched-chain enoyl CoA reductase (14) acyl CoA transferase. 

Although just a few drinks may result in hepatic fat accumulation, chronic consumption of alcohol greatly enhances the development of a fatty liver. Re-esterification of fatty acids into triacylglycerols by fatty acyl CoA transferases in the ER is enhanced (see Fig. 25.6). Because the transferases are microsomal enzymes, they are induced by ethanol consumption just as MEOS is induced. The result is a fatty liver (hepatic steatosis). 

FIGURE 9.2 Physiology of ABE fermentation metabolism of Clostridium acetobutylicum with the respective enzymes and products. CoA, coenzyme A Ldh, lactate dehydrogenase Pdc, pyruvate decarboxylase Pfor, pyruvate ferredoxin oxidoreductase Fdred, ferredoxin reduced Thl, thiolase Hbd, p-hydroxybutyryl-CoA dehydrogenase Crt, crotonase Bed, butyryl-CoA dehydrogenase Etf, electron transfer flavoprotein Pta, phosphotransacetylase Ack, acetate kinase Ptb, phosphotransbutyrylase Buk, butyrate kinase Ctf A/B, acetoacetyl-CoA acyl-CoA transferase Adc, acetoacetate decarboxylase AdhE, aldehyde/alcohol dehydrogenase Bdh, butanol dehydrogenase. 

S.2 Fatty acyl-CoA transferases. The enzyme systems involved with fatty acyl-CoA utilization in the cytosol appear to be membrane-bound. Consequently, detailed knowledge of their individual structure, specificity and genetic control is generally lacking due to the particular inability to obtain ready isolation and purification of the relevant proteins. Studies, however, support the concept of the operation of the eukaryotic pathway for the production of glycerolipids and polyunsaturated fatty acid (Browse et al., 1990 Stymne et al., 1990). While this pathway may contribute a significant quantity of fatty acid for use in membrane synthesis in the plastid (chloroplast) (Browse et al., 1990), its major importance would seem to lie with the production of unsaturated oils (Frentzen, 1986). On the other hand the occurrence of the prokaryotic pathway in the plastid permits more direct membrane lipid formation in both 16 3 and 18 3 plants (Browse et al., 1990 Somerville and Browse, 1991). Different sets of acyltransferase may be associated with the two pathways (Hills and Murphy, 1991). 

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