Substrate-dependent regulation of human arylamine N-acetyltransferase-1 in cultured cells.

作者: Neville J. Butcher , Kenneth F. Ilett , Rodney F. Minchin

DOI: 10.1124/MOL.57.3.468

关键词: EnzymeLactate dehydrogenasePeripheral bloodAcetylationBiologyArylamine N-Acetyltransferase 1Molecular biologyBiochemistrySubstrate (chemistry)Peripheral blood mononuclear cellEC50

摘要: Arylamine N-acetyltransferase-1 (NAT1) is a polymorphically expressed enzyme that widely distributed throughout the body. In present study, we provide evidence for substrate-dependent regulation of this enzyme. Human peripheral blood mononuclear cells cultured in medium supplemented withp-aminobenzoic acid (PABA; 6 μM) 24 h showed significant decrease (50–80%) NAT1 activity. The loss activity was concentration-dependent (EC50 ∼ 2 and selective because PABA had no effect on constitutively lactate dehydrogenase or aspartate aminotransferase. also induced down-regulation several human cell lines grown at confluence. Substrate-dependent not restricted to PABA. Addition other substrates, such as p-aminosalicylic acid, ethyl-p-aminobenzoate, p-aminophenol culture resulted (P

参考文章(31)
E Coroneos, E Sim, Arylamine N-acetyltransferase activity in human cultured cell lines. Biochemical Journal. ,vol. 294, pp. 481- 486 ,(1993) , 10.1042/BJ2940481
R. R. Ramsay, Substrate regulation of monoamine oxidases Journal of Neural Transmission-supplement. ,vol. 52, pp. 139- 147 ,(1998) , 10.1007/978-3-7091-6499-0_15
K. P. Vatsis, W. W. Weber, Human N-Acetyltransferases Handbook of Experimental Pharmacology. ,vol. 112, pp. 109- 130 ,(1994) , 10.1007/978-3-642-78429-3_4
B J Song, R L Veech, S S Park, H V Gelboin, F J Gonzalez, Induction of Rat Hepatic N-Nitrosodimethylamine Demethylase by Acetone Is Due to Protein Stabilization Journal of Biological Chemistry. ,vol. 264, pp. 3568- 3572 ,(1989) , 10.1016/S0021-9258(18)94103-7
Terry V. Zenser, Timothy D. Rustan, Mark A. Doll, Vijaya M. Lakshmi, Bernard B. Davis, David W. Hein, Anne C. Deitz, Human N-Acetylation of Benzidine: Role of NAT1 and NAT2 Cancer Research. ,vol. 56, pp. 3941- 3947 ,(1996)
Henry J. Lin, Nicole M. Probst-Hensch, Nicola C. Hughes, Gordon T. Sakamoto, Andrew D. Louie, Irving H. Kau, Bruce K. Lin, David B. Lee, Jesse Lin, Harold D. Frankl, Eric R. Lee, Steven Hardy, Denis M. Grant, Robert W. Haile, Variants of n -acetyltransferase Nat1 and a case-control study of colorectal adenomas Pharmacogenetics. ,vol. 8, pp. 269- 281 ,(1998) , 10.1097/00008571-199806000-00009
Neville J. Butcher, Kenneth E. Ilett, Rodney F. Minchin, Functional polymorphism of the human arylamine N-acetyltransferase type 1 gene caused by C190T and G560A mutations Pharmacogenetics. ,vol. 8, pp. 67- 72 ,(1998) , 10.1097/00008571-199802000-00009
Edith Sim, Alison Ward, A possible relationship between N-acetyl transferase and folate metabolism Human & Experimental Toxicology. ,vol. 14, pp. 696- 697 ,(1995) , 10.1177/096032719501400812