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 regulated by the acyl-CoA binding protein (ACBP). The ACAT activity is strongly inhibited by different ACBP/oleoyl-CoA complexes depending from the molar ratio of protein and fatty acid-CoA. Other lipid binding proteins such as bovine serum albumin and the liver fatty acid binding protein do not show any effects on ACAT activity. In addition, we can show that cholesterol loading with acetylated low density lipoproteins does not lead to an increase of the ACBP mRNA level. Consequently, the increase of the intracellular concentration of fatty acids because of the cholesteryl ester accumulation renders ACAT more active for cholesterol esterification. In binding studies we have characterized binding sites on microsomal membranes for the ACAT substrate oleoyl-CoA and the ACAT inhibitor diazepam. Diazepam competes with oleoyl-CoA and vice versa for its binding to microsomal membranes. This common binding site is suggested to be responsible for the transfer from ACBP-bound oleoyl-CoA to ACAT and, therefore, to be essential for the microsomal cholesterol esterification.
Kerkhoff
C
C
Institut fur Klinische Chemie und Laboratoriumsmedizin, Klinikum der Universitat Regensburg, Germany.
Beuck
M
M
Threige-Rasmussen
J
J
Spener
F
F
Knudsen
J
J
Schmitz
G
G
D000214:Acyl Coenzyme A / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D015152:Blotting, Northern; D002352:Carrier Proteins / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D002784:Cholesterol / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D026261:Diazepam Binding Inhibitor; D018870:Endoplasmic Reticulum, Rough / Q000201:enzymology; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005445:Flunitrazepam / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D008264:Macrophages / Q000201:enzymology*; D008861:Microsomes / Q000378:metabolism; D009000:Monocytes / Q000201:enzymology*; D018996:Myelin P2 Protein / Q000494:pharmacology; D009363:Neoplasm Proteins; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000378:metabolism*; D025521:Tumor Suppressor Proteins
D000214:Acyl Coenzyme A; D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; C107608:FABP7 protein, human; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; C017585:oleoyl-coenzyme A; D005445:Flunitrazepam; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; D003975:Diazepam