Homocysteine methyltransferases Mht1 and Sam4 prevent the accumulation of age-damaged (R,S)-AdoMet in the yeast Saccharomyces cerevisiae.
Homocysteine methyltransferases Mht1 and Sam4 prevent the accumulation of age-damaged (R,S)-AdoMet in the yeast Saccharomyces cerevisiae.
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同型半胱氨酸甲基转移酶 Mht1 和 Sam4 可防止酿酒酵母中年龄受损的 (R,S)-AdoMet 的积累。
DOI：
10.1074/jbc.m110.113076
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Clarke,StevenG
中科院分区：
文献类型：
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作者：
Vinci,ChrisR;Clarke,StevenG
生物甲基供体 S-腺苷-L-甲硫氨酸 (AdoMet) 通过其锍中心反转而自发降解，形成 R,S 非对映异构体。与其前体 (S,S)-AdoMet 不同，(R,S)-AdoMet 没有已知的细胞功能，并且可能具有一定的毒性。尽管 (R,S)-AdoMet 在生理条件下形成的速率很大，但尚未在多种生物体体内检测到显着水平。这些观察结果表明存在一些机制可以处理 (R,S)-AdoMet 或将其转化回 (S,S)-AdoMet。此前，我们在酵母中鉴定出了两种能够识别和代谢(R,S)-AdoMet的同型半胱氨酸甲基转移酶（Mht1和Sam4）。我们在蠕虫、植物和苍蝇中发现了类似的活动。然而，尚不清楚这些活动是否可以预防 R,S 蓄积。在这项工作中，我们证明Mht1和Sam4酶都能够防止酿酒酵母生长至稳定期时R,S的积累；删除这两个基因会导致显着的 (R,S)-AdoMet 积累。据我们所知，这是首次在任何生物体中报道 (R,S)-AdoMet 的积累。我们表明，酵母细胞可以使用与导入 (S,S)-AdoMet 相同的转运蛋白 (Sam3) 从培养基中摄取 (R,S)-AdoMet。我们的结果表明，酵母细胞已经进化出有效的机制，不仅可以处理 (R,S)-AdoMet 降解产物的自发细胞内生成，而且可以利用环境来源作为营养物质。
The biological methyl donorS-adenosyl-l-methionine (AdoMet) is spontaneously degraded by inversion of its sulfonium center to form theR,Sdiastereomer. Unlike its precursor, (S,S)-AdoMet, (R,S)-AdoMet has no known cellular function and may have some toxicity. Although the rate of (R,S)-AdoMet formation under physiological conditions is significant, it has not been detected at substantial levelsin vivoin a wide range of organisms. These observations imply that there are mechanisms that either dispose of (R,S)-AdoMet or convert it back to (S,S)-AdoMet. Previously, we identified two homocysteine methyltransferases (Mht1 and Sam4) in yeast capable of recognizing and metabolizing (R,S)-AdoMet. We found similar activities in worms, plants, and flies. However, it was not established whether these activities could preventR,Saccumulation. In this work, we show that both the Mht1 and Sam4 enzymes are capable of preventingR,Saccumulation inSaccharomyces cerevisiaegrown to stationary phase; deletion of both genes results in significant (R,S)-AdoMet accumulation. To our knowledge, this is the first time that such an accumulation of (R,S)-AdoMet has been reported in any organism. We show that yeast cells can take up (R,S)-AdoMet from the medium using the same transporter (Sam3) used to import (S,S)-AdoMet. Our results suggest that yeast cells have evolved efficient mechanisms not only for dealing with the spontaneous intracellular generation of the (R,S)-AdoMet degradation product but for utilizing environmental sources as a nutrient.