oleoylCoA

Oleoyl-CoA, also known as (9Z)-octadec-9-enoyl-CoA, is the coenzyme A thioester of oleic acid, a cis-monounsaturated 18-carbon fatty acid. As an activated form of oleate, it serves as a key substrate and intermediate in multiple lipid metabolic pathways.

Formation and localization

Oleoyl-CoA is formed from oleic acid by long-chain acyl-CoA synthetases (ACSL family) in an ATP-dependent reaction that yields AMP and pyrophosphate. It resides in the cytosol and is associated with cellular membranes where lipid synthesis and remodeling occur.

Energy production

In fatty acid catabolism, oleoyl-CoA is transported into the mitochondrion via the carnitine shuttle. Carnitine palmitoyltransferase I (CPT1) converts oleoyl-CoA to oleoyl-carnitine, which is shuttled across the inner mitochondrial membrane and reconverted to oleoyl-CoA by CPT2 in the matrix. Malonyl-CoA can inhibit CPT1 to regulate flux into beta-oxidation. Unsaturated long-chain acyl-CoAs, including oleoyl-CoA, can also undergo beta-oxidation in peroxisomes.

Lipid synthesis and remodeling

Oleoyl-CoA donates acyl groups for glycerolipid biosynthesis. It serves as a substrate for acyltransferases that generate lysophosphatidic acid, phosphatidic acid, diacylglycerol, and triacylglycerol, contributing to membrane phospholipids and neutral lipid storage. It can also participate in phospholipid formation in the endoplasmic reticulum and in sphingolipid pathways.

Elongation and desaturation

As a fatty acyl-CoA, oleoyl-CoA can be elongated by elongases (ELOVL) and further desaturated or modified to form longer or differently unsaturated acyl-CoAs, influencing lipid composition and function.

Regulation and significance

Oleoyl-CoA levels are influenced by ACSL isoforms and cellular energy status, with implications for energy balance, membrane composition, and metabolic disease risk.