Characterization of the Rodent Genes for Arylacetamide Deacetylase, a Putative Microsomal Lipase, and Evidence for Transcriptional Regulation

Trickett, Jeffrey Ianto; Patel, Dilip D.; Knight, Brian L.; Saggerson, E D; Gibbons, Geoffrey F.; Pease, Richard J.

doi:10.1074/jbc.m101764200

Cited by 57 publications

(72 citation statements)

References 67 publications

(63 reference statements)

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“…In the AADAC, CES1, CES2, and UCHL3 genes, other research groups have determined presumed active-site residues (Johnston et al 1997;Pindel et al 1997;Humerickhouse et al 2000;Trickett et al 2001); however, we have found no variations in these regions. As the promoter region of the AADAC gene contains a potential response element for aryl hydrocarbons, which could allow the induction of the gene in response to xenobiotics (Trickett et al 2001), polymorphisms in the 5' flanking region should be investigated intensively.…”

Section: Discussioncontrasting

confidence: 52%

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Catalog of 680 variations among eight cytochrome P450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population

et al. 2003

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We screened DNAs from 48 Japanese individuals for single-nucleotide polymorphisms (SNPs) in eight cytochrome P450 (CYP) genes, nine esterase genes, and two other genes by directly sequencing the relevant genomic regions in their entirety except for repetitive elements. This approach identified 607 SNPs and 73 insertion/deletion polymorphisms among the 19 genes examined. Of the 607 SNPs, 284 were identified in CYP genes, 302 in esterase genes, and 21 in the other two genes (GGT1, and TGM1); overall, 37 SNPs were located in 5' flanking regions, 496 in introns, 55 in exons, and 19 in 3' flanking regions. These variants should contribute to studies designed to investigate possible correlations between genotypes and phenotypes of disease susceptibility or responsiveness to drug therapy.Keywords Single-nucleotide polymorphism (SNP) AE Cytochrome P450 (CYP) AE Esterase AE GGT1 AE TGM1

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Section: Discussioncontrasting

confidence: 52%

“…Arylacetamide deacetylase (AADAC) is an esterase involved in the metabolic activation of arylamine substrates that ultimately become carcinogenic (Probst et al 1991). The AADAC gene is expressed in liver, adrenal cortex, adrenal medulla, and pancreas (Trickett et al 2001).…”

Section: Introductionmentioning

confidence: 99%

Catalog of 680 variations among eight cytochrome P450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population

et al. 2003

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“…The suppression of Aadac by TCDD, TCPOBOP, and PCN was dependent on AhR, CAR, and PXR, respectively. Trickett et al (2001) reported that two PPAR␣ ligands, i.e., fibrate and Wy-14,643, increased Aadac mRNA levels in the intestines but not livers of mice. Consistently, the present findings demonstrate that Aadac mRNA levels in livers of mice are not altered by any of three PPAR␣ ligands.…”

Section: Discussionmentioning

confidence: 99%

“…Hosokawa (1998, 2006) classified the CES/Ces enzymes across species into five groups, on the basis of amino acid homology and substrate selectivity, and revealed that the majority of identified CES/Ces enzymes belong to either the CES1 or CES2 subfamily. Arylacetamide deacetylase (AADAC) (for rodents, Aadac) is an important enzyme in the metabolic activation of arylamine substrates to ultimate carcinogens and also functions as a microsomal lipase during lipoprotein secretion (Probst et al, 1994;Trickett et al, 2001). AADAC/Aadac was categorized into the CES5 family, with a structure different from those of the other four CES families (Satoh and Hosokawa, 2006;Hosokawa et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

Transcription Factor-Mediated Regulation of Carboxylesterase Enzymes in Livers of Mice

Zhang

Cheng²,

Aleksunes³

et al. 2012

Drug Metab Dispos

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ABSTRACT:The induction of drug-metabolizing enzymes by chemicals is one of the major reasons for drug-drug interactions. In the present study, the regulation of mRNA expression of one arylacetamide deacetylase (Aadac) and 11 carboxylesterases (Cess) by 15 microsomal enzyme inducers (MEIs) was examined in livers of male C57BL/6 mice. The data demonstrated that Aadac mRNA expression was suppressed by three aryl hydrocarbon receptor (AhR) ligands, two constitutive androstane receptor (CAR) activators, two pregnane X receptor (PXR) ligands, and one nuclear factor erythroid 2-related factor 2 (Nrf2) activator. Ces1 subfamily mRNA expression was not altered by most of the MEIs, whereas Ces2 subfamily mRNA was readily induced by the activators of CAR, PXR, and Nrf2 but not by peroxisome proliferator-activated receptor ␣ activators.Studies using null mice demonstrated that 1) AhR was required for the 2,3,7,8-tetrachlorodibenzo-p-dioxin-mediated suppression of Aadac and Ces3a; 2) CAR was involved in the 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene-mediated induction of Aadac, Ces2c, Ces2a, and Ces3a; 3) PXR was required for the pregnenolone-16␣-carbonitrile-mediated induction of Aadac, Ces2c, and Ces2a; 4) Nrf2 was required for the oltipraz-mediated induction of Ces1g and Ces2c; and 5) PXR was not required for the DEX-mediated suppression of Cess in livers of mice. In conclusion, the present study systematically investigated the regulation of Cess by MEIs in livers of mice and demonstrated that MEIs modulated mRNA expression of mouse hepatic Cess through the activation of AhR, CAR, PXR, and/or Nrf2 transcriptional pathways.

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“…23) Recently, the enzyme has also been characterized as a microsomal lipase with arylamide deacetylase activity. 24) The mammalian carboxylesterases represent a multigene family, the gene products of which are classified as CES1 to CES4. ES46.5K probably belongs to the CES4 family, as is the case for human acetamide deacetylase.…”

mentioning

confidence: 99%

Stereospecific and Regioselective Hydrolysis of Cannabinoid Esters by ES46.5K, an Esterase from Mouse Hepatic Microsomes, and Its Differences from Carboxylesterases of Rabbit and Porcine Liver

Watanabe

Matsunaga

Kimura

et al. 2005

Biological & Pharmaceutical Bulletin

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Carboxylesterases are a family of enzymes that catalyze the hydrolysis of esters and amides. [1][2][3][4] Carboxylesterases have an important role in the detoxication of xenobiotics and in metabolic activation of prodrugs in some cases. [5][6][7][8] Multiple carboxylesterase isozymes have been purified from various animal species 3,4) including rabbits 9,10) and pigs. 11,12) Although the substrate specificities for many forms of purified carboxylesterases have been well characterized, little is known about their stereospecificity and regioselectivity for the hydrolysis of xenobiotic esters. In relation to the stereospecific hydrolysis of substrates by esterases, enzymatic resolution of enantiomers to obtain a useful chiral starting material has been reported using pig pancreatic lipase. 13,14) Gatley 15) reported that the unusual cocaine enantiomer, (ϩ)-cocaine, was hydrolyzed by butyrylcholine esterase over 2000 times faster than (Ϫ)-cocaine. Maksay et al. 16) reported that esterases in liver and brain homogenates of mice have opposite stereoselectivity in the hydrolysis of the racemate of oxazepam 3-acetate; the hepatic enzyme preferentially hydrolyzes the (R)-enantiomer, whereas the brain enzyme preferentially hydrolyzes the (S)-enantiomer. Yang and Lu 17) also reported that esterases in hepatic microsomes and brain homogenate of rats have the same opposite stereoselectivity in catalyzing the hydrolysis of enantiomeric oxazepam 3-acetate. The catalytic triad Ser/Asp/His is suggested to be a part of oxyanion hole as a catalytic site of various esterases and important for the hydrolysis of substrate esters by the enzymes.18) In addition, structural constraints also affect the interaction of substrates with carboxylesterases. 19) We previously purified the esterase ES46.5K from mouse hepatic microsomes and its role in the metabolism of xenobiotic esters has been characterized. [20][21][22] The enzyme is a 46.5-kDa esterase with considerable homology of the N-terminal amino acid sequence to arylacetamide deacetylase purified from human liver. 23) Recently, the enzyme has also been characterized as a microsomal lipase with arylamide deacetylase activity.24) The mammalian carboxylesterases represent a multigene family, the gene products of which are classified as CES1 to CES4. ES46.5K probably belongs to the CES4 family, as is the case for human acetamide deacetylase. 4)The present study describes the stereospecific and regioselective hydrolysis of cannabinoid esters as model substrates for ES46.5K and carboxylesterases from rabbit and porcine liver. In addition, differences in the characteristics between ES46.5K and the carboxylesterases were also investigated. The properties of ES46.5K, an esterase from mouse hepatic microsomes, were compared with those of carboxylesterases from rabbit and porcine liver. The inhibitory profile with a serine hydrolase inhibitor (bis-p-nitrophenylphosphate) and detergents (sodium dodecylsulfate, Emulgen 911) was different between ES46.5K and the carboxylesterases. Bis MATERIALS ...

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Characterization of the Rodent Genes for Arylacetamide Deacetylase, a Putative Microsomal Lipase, and Evidence for Transcriptional Regulation

Cited by 57 publications

References 67 publications

Catalog of 680 variations among eight cytochrome P450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population

Catalog of 680 variations among eight cytochrome P450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population

Transcription Factor-Mediated Regulation of Carboxylesterase Enzymes in Livers of Mice

Stereospecific and Regioselective Hydrolysis of Cannabinoid Esters by ES46.5K, an Esterase from Mouse Hepatic Microsomes, and Its Differences from Carboxylesterases of Rabbit and Porcine Liver

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