Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Kerkhoff, C; Beuck, M; Threige-Rasmussen, J; Spener, F; Knudsen, J; Schmitz, G.
Acyl-CoA binding protein (ACBP) regulates acyl-CoA:cholesterol acyltransferase (ACAT) in human mononuclear phagocytes.
Biochim Biophys Acta. 1997; 1346(2):163-172
Doi: 10.1016/S0005-2760(97)00030-1
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PubMed
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- Co-Autor*innen der Med Uni Graz
- Spener Friedrich
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Acyl Coenzyme A - metabolism
- Animals -
- Binding, Competitive -
- Blotting, Northern -
- Carrier Proteins - metabolism Carrier Proteins - pharmacology
- Cattle -
- Cholesterol - metabolism
- Diazepam - pharmacology
- Diazepam Binding Inhibitor -
- Endoplasmic Reticulum, Rough - enzymology
- Fatty Acid-Binding Proteins -
- Flunitrazepam - metabolism
- Gene Expression Regulation -
- Humans -
- Macrophages - enzymology
- Microsomes - metabolism
- Monocytes - enzymology
- Myelin P2 Protein - pharmacology
- Neoplasm Proteins -
- Protein Binding -
- RNA, Messenger - metabolism
- Sterol O-Acyltransferase - metabolism
- Tumor Suppressor Proteins -
- Find related publications in this database (Keywords)
- acyl-CoA binding protein
- diazepam binding inhibitor protein
- cholesterol esterification
- acyl-CoA:cholesterol acyltransferase
- peripheral benzodiazepine binding site