Vinci Chris R, Clarke Steven G
Department of Chemistry and Biochemistry and the Molecular Biology Institute, UCLA, Los Angeles, California 90095-1569, USA.
J Biol Chem. 2007 Mar 23;282(12):8604-12. doi: 10.1074/jbc.M610029200. Epub 2007 Jan 30.
The biological methyl donor S-adenosylmethionine (AdoMet) can exist in two diastereoisomeric states with respect to its sulfonium ion. The S configuration, (S,S)-AdoMet, is the only form that is produced enzymatically as well as the only form used in almost all biological methylation reactions. Under physiological conditions, however, the sulfonium ion can spontaneously racemize to the R form, producing (R,S)-AdoMet. As of yet, (R,S)-AdoMet has no known physiological function and may inhibit cellular reactions. In this study, we found two Saccharomyces cerevisiae enzymes that are capable of recognizing (R,S)-AdoMet and using it to methylate homocysteine to form methionine. These enzymes are the products of the SAM4 and MHT1 genes, identified previously as homocysteine methyltransferases dependent upon AdoMet and S-methylmethionine, respectively. We found here that Sam4 recognizes both (S,S)- and (R,S)-AdoMet, but that its activity is much higher with the R,S form. Mht1 reacts with only the R,S form of AdoMet, whereas no activity is seen with the S,S form. R,S-Specific homocysteine methyltransferase activity is also shown here to occur in extracts of Arabidopsis thaliana, Drosophila melanogaster, and Caenorhabditis elegans, but has not been detected in several tissue extracts of Mus musculus. Such activity may function to prevent the accumulation of (R,S)-AdoMet in these organisms.
生物甲基供体S-腺苷甲硫氨酸（AdoMet）就其锍离子而言可存在两种非对映异构状态。S构型，即（S,S）-AdoMet，是唯一通过酶促产生的形式，也是几乎所有生物甲基化反应中使用的唯一形式。然而，在生理条件下，锍离子可自发消旋为R型，产生（R,S）-AdoMet。迄今为止，（R,S）-AdoMet尚无已知的生理功能，可能会抑制细胞反应。在本研究中，我们发现了两种酿酒酵母酶，它们能够识别（R,S）-AdoMet并利用它将同型半胱氨酸甲基化形成甲硫氨酸。这些酶是SAM4和MHT1基因的产物，之前分别被鉴定为依赖于AdoMet和S-甲基甲硫氨酸的同型半胱氨酸甲基转移酶。我们在此发现，Sam4既能识别（S,S）-AdoMet，也能识别（R,S）-AdoMet，但它对R,S形式的活性要高得多。Mht1仅与AdoMet的R,S形式反应，而对S,S形式无活性。本文还表明，R,S特异性同型半胱氨酸甲基转移酶活性也存在于拟南芥、黑腹果蝇和秀丽隐杆线虫的提取物中，但在小家鼠的几种组织提取物中未检测到。这种活性可能起到防止（R,S）-AdoMet在这些生物体中积累的作用。
