RRML - ATP citrate lyase – biology and implication in human pathology

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Dr. Adrian Man

Nr. 12(3)/2008

ATP citrate lyase – biology and implication in human pathology

Liviu S. Enache

Abstract:

ATP citrate lyase (ACLY) is a cytoplasmic enzyme that catalyzes the cleavage of citrate into oxaloacetate and acetyl-CoA. This reaction provides most of the acetyl-CoA required for the biosynthesis of fatty acids and cholesterol. Since its discovery half a century ago, many of the mechanisms involved in the regulation of ACLY activity have remained unclear. Various attempts to biochemically characterize the enzyme gave highly heterogeneous results. The development of expression systems for the recombinant human protein offered a powerful tool for research on this enzyme. Although the reaction catalyzed by ACLY is not rate limiting in either lipogenesis or cholesterologenesis, its „strategic” metabolic position makes ACLY an appealing target for hypolipidemic intervention. ACLY inhibition experiments showing hypolipidemic and hypocholoesterolemic effects in animal models, together with data suggesting the role of the enzyme in cancer biology, cell growth and differentiation, brought it in the attention of scientific community. This paper makes a review of ACLY biology and its potential implication in human pathology.

Keywords: ATP citrate lyase,lipogenesis,enzyme inhibitors,hipolipidemic agents

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Enache LS. ATP citrate lyase – biology and implication in human pathology. Rev Romana Med Lab. 2008;12(3):17-29