小柯机器人

美国加州大学伯克利分校Christopher J. Chang课题组发现，甲醛调节S-腺苷蛋氨酸的生物合成和一碳代谢。这一研究成果于2023年11月3日发表在国际学术期刊《科学》上。

研究人员揭示甲醛（FA），一种源自内源性来源和环境暴露的一碳单位，是如何通过抑制细胞中主要甲基供体S-腺苷蛋氨酸（SAM）的生物合成来调节一碳代谢的。FA会与蛋白质组中的特异性高反应半胱氨酸位点发生反应，包括S-腺苷蛋氨酸合成酶亚型1型（MAT1A）中的Cys120。暴露于FA会抑制MAT1A的活性并减少SAM的产生，而MAT亚型具有特异性。

慢性FA过量的遗传小鼠模型显示，SAM和某些组蛋白及基因的甲基化减少。Mat1a和相关基因的表观遗传和转录调控是对依赖于FA的SAM消耗的补偿机制，进而揭示了FA和SAM一碳单位之间的生化反馈循环。

研究人员表示，一碳代谢是细胞代谢的一个重要分支，与表观遗传调控存在交叉。

附：英文原文

Title: Formaldehyde regulates S-adenosylmethionine biosynthesis and one-carbon metabolism

Author: Vanha N. Pham, Kevin J. Bruemmer, Joel D. W. Toh, Eva J. Ge, Logan Tenney, Carl C. Ward, Felix A. Dingler, Christopher L. Millington, Carlos A. Garcia-Prieto, Mia C. Pulos-Holmes, Nicholas T. Ingolia, Lucas B. Pontel, Manel Esteller, Ketan J. Patel, Daniel K. Nomura, Christopher J. Chang

Issue&Volume: 2023-11-03

Abstract: One-carbon metabolism is an essential branch of cellular metabolism that intersects with epigenetic regulation. In this work, we show how formaldehyde (FA), a one-carbon unit derived from both endogenous sources and environmental exposure, regulates one-carbon metabolism by inhibiting the biosynthesis of S-adenosylmethionine (SAM), the major methyl donor in cells. FA reacts with privileged, hyperreactive cysteine sites in the proteome, including Cys120 in S-adenosylmethionine synthase isoform type-1 (MAT1A). FA exposure inhibited MAT1A activity and decreased SAM production with MAT-isoform specificity. A genetic mouse model of chronic FA overload showed a decrease n SAM and in methylation on selected histones and genes. Epigenetic and transcriptional regulation of Mat1a and related genes function as compensatory mechanisms for FA-dependent SAM depletion, revealing a biochemical feedback cycle between FA and SAM one-carbon units.

DOI: abp9201

Source: https://www.science.org/doi/10.1126/science.abp9201