Enzymatic methylation of arsenic compounds. VI. Characterization of hamster liver arsenite and methylarsonic acid methyltransferase activities in vitro.
Methylation of inorganic arsenic to methylarsonic acid (MMA) and dimethylarsinic acid (DMA) has been considered to be the major pathway of inorganic arsenic biotransformation and detoxification. Comparative studies, in vivo, have demonstrated variation in the abilities of animals to methylate inorganic arsenic. We propose that the rate of inorganic arsenite methylation may be one of the factors responsible for observed species variation. Arsenite and MMA methyltransferases of Golden Syrian hamster liver have been partially purified 40- and 67-fold, respectively. The monothiol L-cysteine promotes greater activities, in vitro, of these enzymes than similar concentrations of either glutathione or dithiothreitol. The pH optima of the partially purified arsenite and MMA methyltransferase activities are 7.6 and 8.0, respectively. Both activities display classic Michaelis-Menten enzyme kinetics. The K(m) and Vmax of hamster liver arsenite methyltransferase are 1.79 x 10(-6) M and 0.022 pmol/mg protein/60 min, respectively. Hamster liver MMA methyltransferase has K(m) and Vmax values of 7.98 x 10(-4) M and 0.007 pmol/mg protein/60 min, respectively. A similar kinetic relationship of these activities is also observed in the liver of the rabbit, which, like the hamster, excretes higher amounts of MMA than most other species studied. The higher K(m) and lower Vmax of MMA methyltransferase, compared to arsenite methyltransferase, measured in these two species suggests that MMA may be produced at a rate higher than it can be subsequently methylated to DMA, thereby allowing MMA to accumulate and be excreted.
Wildfang
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Department of Pharmacology and Toxicology, University of Arizona, Tucson 85721, USA.
Zakharyan
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RA
Aposhian
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HV
D000818:Animals; D001152:Arsenicals / Q000378:metabolism*; D018053:Arsenites / Q000378:metabolism; D006224:Cricetinae; D007700:Kinetics; D008099:Liver / Q000201:enzymology* / Q000378:metabolism; D008647:Mesocricetus; D008745:Methylation; D008780:Methyltransferases / Q000378:metabolism*; D013438:Sulfhydryl Compounds / Q000378:metabolism
D001152:Arsenicals; D018053:Arsenites; D013438:Sulfhydryl Compounds; D008780:Methyltransferases; C116338:arsenite methyltransferase; C116336:methylarsonic acid methyltransferase; C020300:monomethylarsonic acid