Enzymatic Methylation of Arsenic Compounds. VII. Monomethylarsonous Acid (MMA^III) Is the Substrate for MMA Methyltransferase of Rabbit Liver and Human Hepatocytes

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• 作者：Zakharyan ; Robert A. ; Ayala-Fierro ; Felix ; Cullen ; William R. ; Carter ; Dean M. ; Aposhian ; H. Vasken
• 刊名：Toxicology and Applied Pharmacology
• 出版年：1999
• 出版时间：July 1, 1999
• 年：1999
• 卷：158
• 期：1
• 页码：9-15
• 全文大小：86.8 K

文摘

Inorganic arsenite is methylated by some, but not all, animal species to dimethylarsinic acid (DMA). The monomethyl compound containing arsenic in an oxidation state of +3 has been proposed as an intermediate. Using highly purified arsenic methyltransferase from rabbit liver and the partially purified enzyme from Chang human liver hepatocytes, the activity of methylarsonic acid (MMA^V) and methylarsonous acid (MMA^III) as a substrate has been characterized by Michaelis–Menten kinetics. The rabbit liver enzyme has a greater affinity for MMA^III (K_m = 0.92 × 10⁻⁵ M) than MMA^V (K_m = 7.0 × 10⁻⁵ M) since the smaller the K_m the greater the affinity. In addition, a dithiol, reduced lipoic acid or dithiothreitol, appears to be more active than GSH in satisfying the thiol requirement of the enzyme. Although investigators have been unable to detect the arsenic methyltransferase in surgically removed human liver, its presence in Chang human hepatocytes now has been established. The K_m for MMA^III, 3.04 × 10⁻⁶, using MMA^III methyltransferase from Chang human hepatocytes was not greatly different from that of the rabbit liver enzyme.