Human liver arylacetamide deacetylase. Molecular cloning of a novel esterase involved in the metabolic activation of arylamine carcinogens with high sequence similarity to hormone-sensitive lipase.
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Probst MR, Beer M, Beer D, Jeno P, Meyer UA, Gasser R
Human liver arylacetamide deacetylase. Molecular cloning of a novel esterase involved in the metabolic activation of arylamine carcinogens with high sequence similarity to hormone-sensitive lipase.
J Biol Chem. 1994 Aug 26;269(34):21650-6.
- PubMed ID
- 8063807 [ View in PubMed]
- Abstract
Microsomal arylacetamide deacetylase (DAC) competes against the activity of cytosolic arylamine N-acetyltransferase, which catalyzes one of the initial biotransformation pathways for arylamine and heterocyclic amine carcinogens in many species and tissues. Activity determination and immunoblot analysis of DAC in human target tissues for arylamine carcinogens revealed that in extrahepatic tissues, additional enzymes are responsible for any deacetylation activity, whereas a single enzyme predominantly catalyzes this hydrolytic reaction in liver. We isolated and characterized a full-length cDNA from a human liver lambda gt11 library. This clone encodes an open reading frame of 400 amino acids with a deduced molecular mass of 45.7 kDa and contains two putative glycosylation sites. The 3'-untranslated region contains two putative polyadenylation signals. The cDNA was confirmed to be that for DAC in tryptic peptides from the purified human liver protein. Highest sequence similarity of DAC was found in a series of prokaryotic esterases encompassing the putative active site. Two extended regions of significant sequence homology with hormone-sensitive lipase and with lipase 2 from Moraxella TA144 were identified, whereas similarity to carboxyl esterases was restricted to the region encompassing the putative active site, indicating that DAC should be classified as esterase. This cDNA provides an important tool to study deacetylation and its effects on the metabolic activation of arylamine and heterocyclic amine carcinogens.