Research paperEnzyme kinetic properties of human recombinant arylamine n-acetyltransferase 2 allotypic variants expressed in Escherichia coli
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Overview on mechanisms of isoniazid action and resistance in Mycobacterium tuberculosis
2016, Infection, Genetics and EvolutionCitation Excerpt :The so formed acetyl-INH undergoes hydrolysis to form acetyl-hydrazine and the non-toxic substance isonicotinic acid is oxidized to form reactive acylating hepatotoxins, possibly acetyldiazene or its breakdown products consisting of an acetyl radical, an acetylonium ion, and a ketene (Evans et al., 1960; Huang et al., 2002). Human NAT2 enzyme exhibits functional polymorphism and is encoded from a multiallelic locus (Hickman et al., 1995). Thirty-eight single nucleotide polymorphism (SNPs) have been identified in the NAT2 gene coding region.
Isoniazid metabolism and hepatotoxicity
2016, Acta Pharmaceutica Sinica BCitation Excerpt :NAT1 and NAT2 are the major NATs that are involved in the biotransformation of xenobiotics. The NAT genes are located in close vicinity in the genome and share high sequence identity69, but their expression profiles have distinct tissue distribution patterns and the enzymes have different substrate preferences70,71. NAT1 is widely expressed in all tissues, including endocrine tissues, blood cells, neural tissue, liver, and the gastrointestinal tract, whereas NAT2 expression is limited to the liver and gastrointestinal tract72.
HOMOZYGOTES NAT2*5B SLOW ACETYLATORS ARE HIGHLY ASSOCIATED WITH HEPATOTOXICITY INDUCED BY ANTI-TUBERCULOSIS DRUGS
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