AADAC (Human) Recombinant Protein (Q01)
- Known as:
- AADAC (Human) Recombinant Protein (Q01)
- Catalog number:
- H00000013-Q01-25
- Product Quantity:
- 25 ug
- Category:
- -
- Supplier:
- Abno
- Gene target:
- AADAC (Human) Recombinant Protein (Q01)
Related genes to: AADAC (Human) Recombinant Protein (Q01)
- Gene:
- AADAC NIH gene
- Name:
- arylacetamide deacetylase
- Previous symbol:
- -
- Synonyms:
- DAC, CES5A1
- Chromosome:
- 3q25.1
- Locus Type:
- gene with protein product
- Date approved:
- 1996-12-27
- Date modifiied:
- 2018-05-03
- Gene:
- NCEH1 NIH gene
- Name:
- neutral cholesterol ester hydrolase 1
- Previous symbol:
- AADACL1
- Synonyms:
- KIAA1363, NCEH
- Chromosome:
- 3q26.31
- Locus Type:
- gene with protein product
- Date approved:
- 2005-02-25
- Date modifiied:
- 2014-11-19
Related products to: AADAC (Human) Recombinant Protein (Q01)
Related articles to: AADAC (Human) Recombinant Protein (Q01)
- KIAA1363, annotated as neutral cholesterol ester hydrolase 1 (NCEH1), is a member of the arylacetamide deacetylase (AADAC) protein family. The name-giving enzyme, AADAC, is known to hydrolyze amide and ester bonds of a number of xenobiotic substances, as well as clinical drugs and of endogenous lipid substrates such as diglycerides, respectively. Similarly, KIAA1363, annotated as the first AADAC-like protein, exhibits enzymatic activities for a diverse substrate range including the xenobiotic insecticide chlorpyrifos oxon and endogenous substrates, acetyl monoalkylglycerol ether, cholesterol ester, and retinyl ester. Two independent knockout mouse models have been generated and characterized. However, apart from reduced acetyl monoalkylglycerol ether and cholesterol ester hydrolase activity in specific tissues and cell types, no gross-phenotype has been reported. This raises the question of its physiological role and whether it functions as drug detoxifying enzyme and/or as hydrolase/lipase of endogenous substrates. This review delineates the current knowledge about the structure, function and of the physiological role of KIAA1363, as evident from the phenotypical changes inflicted by pharmacological inhibition or by silencing as well as knockout of KIAA1363 gene expression in cells, as well as mouse models, respectively. - Source: PubMed
Publication date: 2022/06/02
Wagner CarinaHois VictoriaTaschler UlrikeSchupp MichaelLass Achim - Flutamide, an antiandrogen drug, is widely used for the treatment of prostate cancer. The initial metabolic pathways of flutamide are hydroxylation and hydrolysis. It was recently reported that the hydrolyzed product, 4-nitro-3-(trifluoromethyl)phenylamine (FLU-1), is further metabolized to N-hydroxy FLU-1, an assumed hepatotoxicant. However, the esterase responsible for the flutamide hydrolysis has not been characterized. In the present study, we found that human arylacetamide deacetylase (AADAC) efficiently hydrolyzed flutamide using recombinant AADAC expressed in COS7 cells. In contrast, carboxylesterase1 (CES1) and CES2, which are responsible for the hydrolysis of many drugs, could not hydrolyze flutamide. AADAC is specifically expressed in the endoplasmic reticulum. Flutamide hydrolase activity was highly detected in human liver microsomes (K(m), 794 +/- 83 microM; V(max), 1.1 +/- 0.0 nmol/min/mg protein), whereas the activity was extremely low in human liver cytosol. The flutamide hydrolase activity in human liver microsomes was strongly inhibited by bis-(p-nitrophenyl)phosphate [corrected], diisopropylphosphorofluoride, and physostigmine sulfate (eserine) but moderately inhibited by sodium fluoride, phenylmethylsulfonyl fluoride, and disulfiram. The same inhibition pattern was obtained with the recombinant AADAC. Moreover, human liver and jejunum microsomes showing AADAC expression could hydrolyze flutamide, but human pulmonary and renal microsomes, which do not express AADAC, showed slight activity. In human liver microsomal samples (n = 50), the flutamide hydrolase activities were significantly correlated with the expression levels of AADAC protein (r = 0.66, p < 0.001). In conclusion, these results clearly showed that flutamide is exclusively hydrolyzed by AADAC. AADAC would be an important enzyme responsible for flutamide-induced hepatotoxicity. - Source: PubMed
Publication date: 2009/04/01
Watanabe AkinobuFukami TatsukiNakajima MikiTakamiya MasatakaAoki YasuhiroYokoi Tsuyoshi