Zakharyan R A, Wildfang E, Aposhian H V
Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721, USA.
Toxicol Appl Pharmacol. 1996 Sep;140(1):77-84. doi: 10.1006/taap.1996.0199.
The methylation of inorganic arsenic to monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) have been generally considered to be the major pathway for inorganic arsenic biotransformation and detoxification. Yet, when arsenate/arsenite is injected into the Callithrix jacchus (marmoset) monkey or chimpanzee, monomethylarsonic acid and dimethylarsinic acid are not found in the urine. With the development of a rapid assay for the methyltransferases of arsenic metabolism, we have investigated the methyltransferases of the marmoset monkey liver. We have found that the marmoset, a New World animal, is deficient in liver arsenite and monomethylarsonic acid methyltransferase activities. However, the rhesus monkey, an Old World animal, has ample amounts of such methyltransferase activities. The tamarin, another New World species, is also deficient in these methyltransferases. Polymorphism and deficiency of these methyltransferases may have allowed high levels of arsenite to be maintained in the blood and liver of the marmoset and tamarin. Such high levels of arsenite may have been selective for survival of the species. The rhesus liver methyltransferases for arsenite and MMA have been purified and found to have some properties different from those of the previously reported purified rabbit liver activities. The rhesus and rabbit liver arsenite and MMA methyltransferases are devoid of catechol O-methyltransferase activity.
无机砷甲基化生成一甲基胂酸（MMA）和二甲基胂酸（DMA）通常被认为是无机砷生物转化和解毒的主要途径。然而，当将砷酸盐/亚砷酸盐注入狨猴（绢毛猴）或黑猩猩体内时，尿液中并未发现一甲基胂酸和二甲基胂酸。随着砷代谢甲基转移酶快速检测方法的发展，我们对狨猴肝脏中的甲基转移酶进行了研究。我们发现，作为一种新大陆动物，狨猴肝脏中的亚砷酸盐和一甲基胂酸甲基转移酶活性不足。然而，作为一种旧大陆动物，恒河猴具有充足的此类甲基转移酶活性。绢毛猴，另一种新大陆物种，也缺乏这些甲基转移酶。这些甲基转移酶的多态性和缺乏可能使得狨猴和绢毛猴血液和肝脏中维持较高水平的亚砷酸盐。如此高的亚砷酸盐水平可能对该物种的生存具有选择性。恒河猴肝脏中用于亚砷酸盐和MMA的甲基转移酶已被纯化，并且发现其某些特性与先前报道的纯化兔肝脏活性不同。恒河猴和兔肝脏中的亚砷酸盐和MMA甲基转移酶缺乏儿茶酚-O-甲基转移酶活性。
