College of Ecology and Environmental Sciences, Yunnan University, Kunming, 650091, PR China.
College of Ecology and Environmental Sciences, Yunnan University, Kunming, 650091, PR China.
Mutat Res Rev Mutat Res. 2021 Jul-Dec;788:108396. doi: 10.1016/j.mrrev.2021.108396. Epub 2021 Oct 7.
Enzymatic methylation catalyzed by methyltransferases has a significant impact on many human biochemical reactions. As the second most ubiquitous cofactor in humans, S-adenosyl-l-methionine (SAM or AdoMet) serves as a methyl donor for SAM-dependent methyltransferases (MTases), which transfer a methyl group to a nucleophilic acceptor such as O, As, N, S, or C as the byproduct. SAM-dependent methyltransferases can be grouped into different types based on the substrates. Here we systematically reviewed eight types of methyltransferases associated with human diseases. Catechol O-methyltransferase (COMT), As(III) S-adenosylmethionine methyltransferase (AS3MT), indolethylamine N-methyltransferase (INMT), phenylethanolamine N-methyltransferase (PNMT), histamine N-methyltransferase (HNMT), nicotinamide N-methyltransferase (NNMT), thiopurine S-methyltransferase (TPMT) and DNA methyltansferase (DNMT) are classic SAM-dependent MTases. Correlations between genotypes and disease susceptibility can be partially explained by genetic polymorphisms. The physiological function, substrate specificity, genetic variants and disease susceptibility associated with these eight SAM-dependent methyltransferases are discussed in this review.
酶促甲基化反应由甲基转移酶催化，对许多人体生化反应有重要影响。S-腺苷甲硫氨酸（SAM 或 AdoMet）是人体内第二大普遍存在的辅因子，作为 SAM 依赖性甲基转移酶（MTases）的甲基供体，将甲基转移到亲核受体如 O、As、N、S 或 C 上，生成副产物。SAM 依赖性甲基转移酶可根据底物分为不同类型。本文系统综述了与人类疾病相关的 8 种甲基转移酶。儿茶酚-O-甲基转移酶（COMT）、砷（III）S-腺苷甲硫氨酸甲基转移酶（AS3MT）、吲哚乙胺 N-甲基转移酶（INMT）、苯乙醇胺 N-甲基转移酶（PNMT）、组氨酸 N-甲基转移酶（HNMT）、烟酰胺 N-甲基转移酶（NNMT）、硫嘌呤 S-甲基转移酶（TPMT）和 DNA 甲基转移酶（DNMT）是经典的 SAM 依赖性 MTases。基因多态性部分解释了基因型与疾病易感性之间的相关性。本文讨论了这 8 种 SAM 依赖性甲基转移酶的生理功能、底物特异性、遗传变异和疾病易感性。
