Unesterified sterol modulates the function of all eukaryotic cell membranes. Two genes have been identified, ARE1 and ARE2, that encode ACAT related enzymes required for sterol esterification in yeast. Disruption of ARE1 produces cells with no detectable reduction in sterol ester levels relative to wild type strains.
Human cells show a similar situation conceptually.
In addition to the first ACAT to be identified at the molecular level, two new human sequences have been identified which are candidates for additional tissue specific human ACAT enzymes. These human enzymes are likely to play a major role in cardiovascular disease and potentially obesity. This therapeutic method addresses the problems of hypercholesterolemia and atherosclerosis. The mehtod serves as a plasma cholesterol lowering treatment. If the enzyme encoded by the gene is inhibited, toxicity and efficacy problems with pre-existing inhibitors, would be overcome.