ACYL-COA-BINDING PROTEIN (ACBP) REGULATES ACYL-COA-CHOLESTEROL ACYLTRANSFERASE (ACAT) IN HUMAN MONONUCLEAR PHAGOCYTES

It is demonstrated that the acyl-CoA:cholesterol acyltransferase (ACAT ) enzyme activity in rough endoplasmatic reticulum membranes is regula ted by the acyl-CoA binding protein (ACBP). The ACAT activity is stron gly inhibited by different ACBP/oleoyl-CoA complexes depending from th e molar ratio of protein and fatty acid-CoA. Other lipid binding prote ins such as bovine serum albumin and the liver fatty acid binding prot ein do not show any effects on ACAT activity. In addition, we can show that cholesterol loading with acetylated low density lipoproteins doe s not lead to an increase of the ACBP mRNA level. Consequently, the in crease of the intracellular concentration of fatty acids because of th e cholesteryl ester accumulation renders ACAT more active for choleste rol esterification. In binding studies we have characterized binding s ites on microsomal membranes for the ACAT substrate oleoyl-CoA and the ACAT inhibitor diazepam. Diazepam competes with oleoyl-CoA and vice v ersa for its binding to microsomal membranes. This common binding site is suggested to be responsible for the transfer from ACBP-bound oleoy l-CoA to ACAT and, therefore, to be essential for the microsomal chole sterol esterification.