ACAT Genes and Proteins in Humans

Acyl-coenzyme Axholesterol acyltransferase (ACAT) is an intracellular enzyme present in a variety of tissues. It plays important roles in cellular cholesterol homeostasis, in producing cholesteryl esters present in VLDLs and chylomicrons, and in causing foam cell formation in atherosclerosis. Two ACAT genes have been identified in mammals: ACAT-1 gene in 1993 and ACAT-2 gene in 1998. Specific antibodies against ACAT-1 protein and ACAT-2 have become available. In this article, we summarize our recent findings regarding: (1) the mode of regulation of ACAT-1 protein by sterol in human HepG2 cells; (2) the expression patterns of ACAT-1 protein in human atherosclerotic lesions, and in human monocyte-macrophages in culture; (3) the distribution of ACAT-1 protein in human tissues; our results suggest that the ACAT-1 protein plays a major catalytic role in various adult tissues including liver, adrenal gland, kidney, and macrophages, but not in the intestines; most of the ACAT activity found in the human intestines is probably due to the presence of ACAT-2; (4) the full-length cDNA sequence of human ACAT-2 cloned from a human intestinal library; (5) a procedure for purifying the recombinant human ACAT-1 protein to electrophoretic homogeneity with retention in enzymatic activity; (5) the kinetic properties of the pure human ACAT-1 protein; our results support the hypothesis that ACAT-1 is an allosteric enzyme regulated by cholesterol. We also propose that in hepatocytes, the allosteric character of ACAT-1 enables it to utilize cholesterol synthesized de novo to produce cholesteryl esters for VLDL assembly.