General CoA-dependent acyltransferases and ligases

General CoA-dependent acyltransferases and ligases represent a broad superfamily of enzymes that utilize Coenzyme A (CoA) as a central cofactor to catalyze the transfer of acyl groups to various substrates or the ligation of carboxylic acids to CoA. This classification encompasses several critical metabolic enzyme families, including diacylglycerol acyltransferases (DGAT), acyl-CoA:cholesterol acyltransferases (ACAT), and histone acetyltransferases (HATs), as well as various acyl-CoA synthetases. These enzymes are essential for the biosynthesis of complex lipids such as triacylglycerols and cholesterol esters, and they play pivotal roles in cellular energy storage, membrane structure, and epigenetic regulation. Due to their fundamental involvement in lipid homeostasis, they are primary therapeutic targets for metabolic disorders like obesity, type 2 diabetes, and atherosclerosis. Furthermore, pharmacological modulation of these enzymes is being explored in oncology and inflammatory diseases to address metabolic reprogramming and aberrant gene expression. Small-molecule inhibitors designed for these targets typically aim to block the binding of acyl-CoA or the acceptor substrate, thereby altering lipid profiles or cellular signaling pathways.

Other names

CoA-dependent acyltransferasesAcyl-CoA ligasesAcyl-CoA dependent acyltransferasesAcyltransferases and ligasesGNAT superfamily enzymes

Inhibition of acyl group transfer from acyl-CoA to substrates or inhibition of carboxylic acid ligation to Coenzyme A to modulate lipid flux and protein modification.