Roles of acyl-coenzyme A : cholesterol acyltransferase-1 and-2

Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is an intracellular enzy me that produces cholesteryl esters in various tissues. In mammals, two ACA T genes (ACAT1 and ACAT2) have been identified. Together, these two enzymes are involved in storing cholesteryl esters as lipid droplets, in macrophag e foam-cell formation. in absorbing dietary cholesterol, and in supplying c holesteryl esters as part of the core lipid for lipoprotein synthesis and a ssembly. The key difference in tissue distribution of ACAT1 and ACAT2 betwe en humans, mice and monkeys is that, in adult human liver (including hepato cytes and bile duct cells), the major enzyme is ACAT1, rather than ACAT2. T here is compelling evidence implicating a role for ACAT1 in macrophage foam -cell formation, and for ACAT2 in intestinal cholesterol absorption. Howeve r, further studies at the biochemical and cell biological levels are needed in order to clarify the functional roles of ACAT1 and ACAT2 in the VLDL or chylomicron synthesis/assembly process. Curr Opin Lipidol 12:280-296 (C) 2 001 Lippincott Williams & Wilkins.