Acyl transferase enzymes

A catalytic effect that may be of the same type as the mimicry of acyl transferase enzymes is reported by Gandour et al. (1978). They describe the rate enhancement of the aminolysis of p-nitrophenyl acetate in the presence of bis(2,6-pyridinyl) crown ethers [328] and [329] in chlorobenzene. The rate of... 

N,0-Acyltransferase. The /V-acyl transferase enzyme is believed to be involved in the carcinogenicity of arylamines. These compounds are first V-oxidized, and then, in species capable of their A-acetylation, acetylated to arylhydroxamic acids. The effect of N, O-transacetylation is shown in Figure 7.22. The A/-acyl group of the hydroxamic acid is first removed and is then transferred, either to an amine to yield a stable amide or to the oxygen of the hydroxylamine to yield a reactive N-acyloxyarylaminc. These compounds are highly reactive in the formation of adducts with both proteins and nucleic acids, and N, O -acy I Iransfcrasc, added to the medium in the Ames test, increases the mutagenicity of compounds such as A-hydroxy-2-acetylaminofluorine. 

Bieber LL, Farel SS. Carnitine acyl transferases. Enzymes 1983 16 624-644. 

Acyl transferase enzymes have been widely used to synthesize chiral esters, amides, alcohols, and amines. In many cases, these conversions involve kinetic resolutions of alcohols, adds, esters, amines, and amides. Of course, since each enantiomer makes up half of the racemic mixture, kinetic resolutions can provide a maximum 50% yield. This limitation can be overcome by racemizing or inverting the configuration of the unreacted substrate during the enzymatic reaction. Such a scheme is referred to as a dynamic kinetic resolution and theoretically allows complete substrate conversion to product along with 100% chemical yield of a single product enantiomer. 

Tocotrienols present in rice bran inhibit the liver microsomal enzyme HMGCoA reductase (Qureshi and Qureshi, 1992), the key enzyme involved in the endogenous synthesis of cholesterol, and this helps to lower the circulating cholesterol. Inhibition of another enzyme, ACAT (Acyl coenzyme A acyl transferase), by y-oryzanol results in lowered LDL-C synthesis and enrichment... 

At this point, the acyl-CoA is still in the cytosol of the muscle cell. Entry of the acyl-CoA into the mitochondrial matrix requires two translocase enzymes, carnitine acyl transferase I and carnitine acyl transferase II (CAT I and CAT II), and a carrier molecule called carnitine the carnitine shuttles between the two membranes. The process of transporting fatty acyl-CoA into mitochondria is shown in Figure 7.15. 

The initial acylation at the 1-position of glycerol 3-phosphate is catalysed by glycerol 3-phosphate acyl-transferase-1, abbreviated to GPAT-1. This enzyme is specific for a saturated fatty acid (in the acyl form). 

This enzyme [EC 2.3.1.26], also known as sterol O-acyl-transferase, sterol-ester synthase, and cholesterol acyl-transferase, catalyzes the reaction of an acyl-coenzyme A derivative with cholesterol to produce coenzyme A and the cholesterol ester. The animal enzyme is highly specific for transfer of acyl groups having a single cis double bond at C9. 

This enzyme [EC 2.3.1.23], also called lysolecithin acyl-transferase and lysophosphatidylcholine acyltransferase, catalyzes the reaction of an acyl-CoA derivative with 1-acyl-5 n-glycero-3-phosphocholine to yield coenzyme A and l,2-diacyl-5 n-glycero-3-phosphocholine. The enzyme preferentially acts on unsaturated acyl-CoA derivatives, but l-acyl-5 n-glycero-3-phosphoinositol can also act as the acceptor. 

Glycine A-benzoyltransferase [EC 2.3.1.71] catalyzes the reaction of benzoyl-CoA with glycine to produce coenzyme A and A-benzoylglycine. This enzyme is not identical with glycine A-acyltransferase or glutamine A-acyl-transferase [EC 2.3.1.68]. 

Incorporation of different fatty acids into lipids depends on the relative abundance of their CoA derivatives and their acyl-transferase )< , values. The synthetic enzymes which form membrane phospholipids may select the acid by molecular features not in accord with the optimal physiological properties of the products (110), resulting in the formation of membranes which do not function adequately. 

Much of the cholesterol synthesis in vertebrates takes place in the liver. A small fraction of the cholesterol made there is incorporated into the membranes of he-patocytes, but most of it is exported in one of three forms biliary cholesterol, bile acids, or cholesteryl esters. Bile acids and their salts are relatively hydrophilic cholesterol derivatives that are synthesized in the liver and aid in lipid digestion (see Fig. 17-1). Cholesteryl esters are formed in the liver through the action of acyl-CoA-cholesterol acyl transferase (ACAT). This enzyme catalyzes the transfer of a fatty acid from coenzyme A to the hydroxyl group of cholesterol (Fig. 21-38), converting the cholesterol to a more hydrophobic form. Cholesteryl esters are transported in secreted lipoprotein particles to other tissues that use cholesterol, or they are stored in the liver. 

The fourth major lipoprotein type, high-density lipoprotein (HDL), originates in the liver and small intestine as small, protein-rich particles that contain relatively little cholesterol and no cholesteryl esters (Fig. 21-40). HDLs contain apoA-I, apoC-I, apoC-II, and other apolipoproteins (Table 21-3), as well as the enzyme lecithin-cholesterol acyl transferase (LCAT), which catalyzes the formation of cholesteryl esters from lecithin (phosphatidylcholine) and cholesterol (Fig. 21-41). LCAT on the surface of nascent (newly forming) HDL particles converts the cholesterol and phosphatidylcholine of chylomicron and VLDL remnants to cholesteryl esters, which begin to form a core, transforming the disk-shaped nascent HDL to a mature, spherical HDL particle. This cholesterol-rich lipoprotein then returns to the liver, where the cholesterol is unloaded some of this cholesterol is converted to bile salts. 

FIGURE 21-41 Reaction catalyzed by lecithin-cholesterol acyl transferase (LCAT). This enzyme is present on the surface of HDL and is stimulated by the HDL component apoA-I. Cholesteryl esters accumulate within nascent HDLs, converting them to mature HDLs. 

One enzyme regulated by AMPK is acetyl-CoA carboxylase, which produces malonyl-CoA, the first intermediate committed to fatty acid synthesis. Malonyl-CoA is a powerful inhibitor of the enzyme carnitine acyl-transferase I, which starts the process of ]3 oxidation by transporting fatty acids into the mitochondrion (see Fig. 17-6). By phosphorylating and inactivating acetyl-CoA carboxylase, AMPK inhibits fatty acid synthesis while relieving the inhibition (by malonyl-CoA) of )3 oxidation (Fig. 23-37). 

Citrate lyase catalyzes the cleavage of citrate to oxaloacetate and acetate in the presence of Mg2+ or Mn2+, but in the presence of EDTA it catalyzes its synthesis. The enzyme is a complex of three subunits. The y-subunit functions as an acyl carrier protein (ACP). The a-subunit is an acyl transferase involved in citryl-ACP formation and the release of acetate, and the /8-subunit catalyzes the cleavage of the citryl-ACP intermediate to oxaloacetate and acetyl-ACP. The enzyme from Klebsiella aerogenes has been purified, and binds 18 Mn2"1 in a cooperative manner. 

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