Sterol carrier protein-2 suppresses microsomal acyl-CoA hydrolysis

Although sterol carrier protein 2 (SCP-2) has long been regarded primarily as a sterol transfer protein, its actual physiological function is not know n. The recent discovery that SCP-2 binds long chain fatty acyl-CoAs (LCFA-C oAs) with high affinity suggests additional roles for SCP-2 in cellular uti lization of LCFA-CoAs for synthesis of glycerides and cholesterol esters. C oncomitant to these anabolic pathways, LCFA-CoAs are also degraded by cellu lar hydrolases. The purpose of the work presented herein was to determine i f SCP-2 altered the aqueous pool of LCFA-CoA by (i) extracting LCFA-CoA fro m microsomal membranes, and (ii) protecting LCFA-CoA from microsomal hydrol ase activity. The data demonstrated for the first time that SCP-2 increases the aqueous pool of oleoyl-CoA by increasing the aqueous/membrane distribu tion oleoyl-CoA by 2.4-fold. In addition, SCP-2 inhibited the hydrolysis of oleoyl-CoA by microsomal acyl-CoA hydrolase 1.6-2.4 fold, depending on the concentration of oleoyl-CoA. By simultaneously extracting LCFA-CoA from me mbranes and inhibiting LCFA-CoA degradation SCP-2 may potentiate LCFA-CoA t ransacylation and modulate the role of LCFA-CoAs as intracellular signaling molecules.