Excess S-adenosylmethionine inhibits methylation via catabolism to adenine.
Excess S-adenosylmethionine inhibits methylation via catabolism to adenine.
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过量的s -腺苷蛋氨酸通过分解代谢腺嘌呤抑制甲基化。
DOI：
10.1038/s42003-022-03280-5
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发表时间：
2022-04-05
影响因子：
5.9
通讯作者：
Fustin JM
中科院分区：
文献类型：
--
作者：
Fukumoto K;Ito K;Saer B;Taylor G;Ye S;Yamano M;Toriba Y;Hayes A;Okamura H;Fustin JM
全球膳食补充剂市场价值超过1000亿美元。一种流行的膳食补充剂S-腺苷甲硫氨酸自1999年以来在美国上市，以改善关节，肝脏健康和情绪健康，自1975年以来一直是欧洲治疗抑郁症和关节炎的处方药，但最近的研究质疑其疗效。在我们的身体中，S-腺苷甲硫氨酸对于核酸、蛋白质和许多其他靶点的甲基化至关重要。SAM的销售意味着更多的S-腺苷甲硫氨酸更好，因为它会刺激甲基化并改善健康。以前，我们已经表明甲基化反应调节许多生物体的生物节律。在这里，使用生物节律来评估外源性S-腺苷甲硫氨酸的影响，我们发现，过量的S-腺苷甲硫氨酸破坏节奏，而不是促进甲基化，被分解代谢为腺嘌呤和甲硫腺苷，有毒的甲基化抑制剂。这些发现进一步加深了我们对甲基代谢的理解，并质疑S-腺苷蛋氨酸作为补充剂的安全性。S-腺苷甲硫氨酸（SAM）是一种广泛使用的膳食补充剂。外源性SAM被分解代谢为腺嘌呤，腺嘌呤是腺苷高半胱氨酸酶的抑制剂，导致广泛的甲基化抑制和体外和小鼠昼夜节律的破坏。
The global dietary supplement market is valued at over USD 100 billion. One popular dietary supplement, S-adenosylmethionine, is marketed to improve joints, liver health and emotional well-being in the US since 1999, and has been a prescription drug in Europe to treat depression and arthritis since 1975, but recent studies questioned its efficacy. In our body, S-adenosylmethionine is critical for the methylation of nucleic acids, proteins and many other targets. The marketing of SAM implies that more S-adenosylmethionine is better since it would stimulate methylations and improve health. Previously, we have shown that methylation reactions regulate biological rhythms in many organisms. Here, using biological rhythms to assess the effects of exogenous S-adenosylmethionine, we reveal that excess S-adenosylmethionine disrupts rhythms and, rather than promoting methylation, is catabolized to adenine and methylthioadenosine, toxic methylation inhibitors. These findings further our understanding of methyl metabolism and question the safety of S-adenosylmethionine as a supplement. S-adenosylmethionine (SAM) is a widely available dietary supplement. Exogenous SAM is catabolized to adenine, an inhibitor of adenosylhomocysteinase, leading to widespread methylation inhibition and disruption of circadian rhythms in vitro and in mice.
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影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
DOI：
10.1073/pnas.1721371115
发表时间：
2018-06-05
影响因子：
11.1
作者：
Fustin JM;Kojima R;Itoh K;Chang HY;Ye S;Zhuang B;Oji A;Gibo S;Narasimamurthy R;Virshup D;Kurosawa G;Doi M;Manabe I;Ishihama Y;Ikawa M;Okamura H
通讯作者：
Okamura H
影响因子：
16
作者：
Haws, Spencer A.;Yu, Deyang;Denu, John M.
通讯作者：
Denu, John M.
S-腺苷-L-氢绿碱水解酶将蛋氨酸代谢与昼夜节律的时钟和染色质重塑联系在一起。
影响因子：
13.6
作者：
Greco CM;Cervantes M;Fustin JM;Ito K;Ceglia N;Samad M;Shi J;Koronowski KB;Forne I;Ranjit S;Gaucher J;Kinouchi K;Kojima R;Gratton E;Li W;Baldi P;Imhof A;Okamura H;Sassone-Corsi P
通讯作者：
Sassone-Corsi P
DOI：
10.1016/j.biocel.2003.11.016
发表时间：
2004-11-01
影响因子：
4
作者：
Avila, MA;García-Trevijano, ER;Mato, JM
通讯作者：
Mato, JM