Introduction
Acyl-Coenzyme A Cholesterol Acyltransferase (ACAT), or also known as Sterol O-Acyltransferase (SOAT), is an important enzyme in the body.
Cholesterol esters were found in arterial lesions in 1910, but the first ACAT activity was discovered in the mid 1900's. This led to the inhibition of ACAT as being looked at as a possible strategy of preventing or treating atherosclerosis. Between 1980-1995, the interest in ACAT inhibitors grew, but some of the compounds looked at exhibited toxicity. As they were looking into the function of the ACAT1 gene, ACAT2 was discovered. In 1993, an ACAT gene was successfully cloned. This discovery led to more studies with ACAT and atherosclerosis. Some of these studies used mice and showed cellular toxicity. ACAT inhibition is still being looked into as a strategy for treatment or prevention of atherosclerosis and related diseases.
[1]
add more history
Figure 1. ACAT as a Dimer of Dimers - One Monomer is Highlighted
Function
ACAT is an important enzyme that catalyzes the esterification of cholesterol to form cholesterol esters.
SOAT article [2]
ACAT article [3]
Disease
atherosclerosis, Alzheimer's Disease
Structural highlights
ACAT is a dimer of dimers, which is also known as a tetramer.
This
is about 260 kDa and is composed completely of helices, with each monomer containing 9 transmembrane helices.
The
was found to be the active arrangement.
The
is mobile and mostly hydrophobic.
Relevance
talk about inhibitor CI-976
Figure 2. CI-976 Inhibitor
