Carnitine O-acetyltransferase (CRAT)

Carnitine O-acetyltransferase (CRAT) is a mitochondrial enzyme that catalyzes the reversible exchange of acetyl groups between coenzyme A (CoA) and carnitine. This reaction produces either acetylcarnitine plus CoA from carnitine plus acetyl-CoA or vice versa. The enzyme plays an essential role in cellular energy homeostasis by regulating the pool sizes of free CoA and acyl-CoAs within mitochondria. Structurally, CRAT consists of two domains with similar backbone folds; its active site features a catalytic histidine residue critical for substrate deprotonation during catalysis. Deficiency in this enzyme leads to severe neurological and cardiac symptoms due to impaired energy metabolism. It has emerged as an attractive therapeutic target for metabolic diseases like type 2 diabetes and obesity because modulation affects lipid utilization pathways without directly altering glucose handling mechanisms.[1][3][4][5][6]

Other names

Carnitine acetyltransferaseCrATCAT (less common, can be ambiguous)EC 2.3.1.7 (Enzyme Commission number)

Drugs or small molecules targeting CRAT would typically act by inhibiting or modulating its enzymatic activity—altering the transfer of acetyl groups between CoA and carnitine, thereby affecting mitochondrial metabolism and fatty acid oxidation rates[3].