ACAT-2

Background: Cholesterol esterification in mammals is catalyzed by the intracellular enzyme acyl CoA:cholesterol acyltransferase (ACAT). In addition to its role in cellular cholesterol homeostasis, ACAT is important in several physiologic processes including intestinal cholesterol absorption, hepatic lipoprotein production, and the development of atherosclerotic lesions. Mouse tissue expression studies and the disruption of the mouse ACAT gene have indicated that more than one ACAT exists in mammals and, specifically, that another cholesterol acyltransferase enzyme is evident in mouse liver and intestine.

Description: Researchers at the Gladstone Institutes have recently cloned the mouse and human cDNAs for the second ACAT enzyme, ACAT-2, and have identified that ACAT-2 mRNA is found primarily in mouse liver and intestine. This finding suggests that ACAT-2 is responsible for cholesterol esterification in these tissues. ACAT-2 exhibits a high specific activity with cholesterol as well as other oxysterol substrates, whereas ACAT-1 appears to be more active with oxysterols than with cholesterol. In addition, ACAT-2 exhibits different sensitivities from ACAT-1 towards various inhibitors.

Applications: The availability of ACAT-2 reagents would facilitate the development of specific ACAT inhibitors that selectively target different forms of ACAT, for example, macrophage-derived ACAT-1, which is involved in atherosclerosis, and ACAT-2, which may be important in cholesterol absorption or lipoprotein assembly.

Advantages: The Gladstone ACAT-2 gene would allow in vivo studies, such as gene disruption, which could elucidate the role of ACAT-2 in mammalian biology. Such studies were of major importance in defining the physiological role of ACAT-1.

Reference: 1998-239

Gladstone Contact: Caryl Cachola
Telephone: 415-734-2082

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