StearoylCoA

Stearoyl-CoA, the CoA thioester of stearic acid (18:0), is formed in cells by long-chain acyl-CoA synthetases (ACSLs) that activate free stearic acid with ATP and CoA. As a central metabolic intermediate, stearoyl-CoA participates in both the catabolic and anabolic pathways of fatty acid metabolism.

In fatty acid oxidation, long-chain acyl-CoAs are transported into mitochondria via carnitine palmitoyltransferase I (CPT1), which forms acylcarnitines for mitochondrial entry. Inside the mitochondrion, CPT2 reconverts them to acyl-CoAs for beta-oxidation, generating acetyl-CoA through successive cycles and gradually shortening the fatty acyl chain.

In lipid biosynthesis, stearoyl-CoA serves as a substrate for the assembly of complex lipids, including triglycerides and phospholipids. It can be incorporated into glycerolipid backbones through acyltransferase reactions, contributing to the formation of glycerol-3-phosphate derivatives and subsequent lipid products. Stearoyl-CoA is also the preferred substrate for stearoyl-CoA desaturase (SCD), particularly the SCD1 isoform, which desaturates it to oleoyl-CoA (18:1). The resulting monounsaturated fatty acid is a major component of membrane phospholipids and stored lipids and influences membrane fluidity and lipid synthesis.

Regulation of stearoyl-CoA metabolism intersects with metabolic health; altered ACSL activity and SCD expression can affect tissue lipid composition, energy homeostasis, and disease states such as obesity and metabolic syndrome.