Acyltransferases

Acyltransferase inhibitors act on enzymes that transfer acyl groups from coenzyme A thioesters. Such reactions build cholesteryl esters, triacylglycerols and acylated proteins, so these enzymes sit at branch points of lipid metabolism. Human acyl-coenzyme A:cholesterol acyltransferase 1 (ACAT1) was cloned in 1993, and nevanimibe, CI 976 and VULM 1457 inhibit these cholesterol acyltransferases. PF-06471553 inhibits monoacylglycerol acyltransferase 3 (MGAT3), which forms diacylglycerol during intestinal lipid absorption. GOAT-IN-1 blocks ghrelin O-acyltransferase (GOAT), identified in 2008 as the enzyme that attaches octanoate to the hormone ghrelin. Etomoxir (sodium salt) inhibits carnitine palmitoyltransferase 1 (CPT-1), which commits fatty acids to mitochondrial oxidation. Enzymes that instead hydrolyze lipids appear under the sibling categories Lipase and Phospholipases.