Methylation

Methylation is a common but minor pathway of Phase II conjugation compared to glucuronidation or sulfonation. The cofactor used in methylation conjugation is S-adenosylmethionine (SAM). SAM is the second most widely used enzyme substrate after ATP and is involved in a wide range of important biological processes. SAM is sythesized from methionine's reaction with ATP, catalyzed by methionine adenosyltransferase (MAT). There are two genes, MAT1A and MAT2A, which encode for two homologous MAT catalytic subunits, 1 and 2.<br>During conjugation with nucleophilic substrates, the methyl group attached to the sulfonium ion of SAM is transferred to the substrate forming the conjugate. SAM, having lost the methyl moiety, is converted to S-adenosylhomocysteine (SAH). SAH can be hydrolyzed to form adenosine and homocysteine. Homocysteine can either be converted to glutathione or methylated to form methionine, thus forming the starting point for SAM synthesis and completing the cycle.<br>Fuctional groups attacked are phenols, catechols, aliphatic and aromatic amines and sulfhydryl-containing groups. The enzymes that catalyze the transfer of the methyl group to these functional groups are the methyltransferases (MT). MTs are small, cytosolic, monomeric enzymes that utilize SAM as a methyl donor. There are many MTs but the best studied ones are named on the basis of their prototypical substrates: <i><b>COMT</b> (catechol O-methyltransferase)</i>, <i><b>TPMT</b> (thiopurine methyltransferase)</i>, <i><b>TMT</b> (thiol methyltransferase)</i>, <i><b>HNMT</b> (histamine N-methyltransferase)</i> and <i><b>NNMT</b> (nicotinamide N-methyltransferase)</i>. An example of each enzyme mentioned is given. In each case, a typical substrate for the enzyme is shown.

甲基化相较于糖基化或硫酸化而言，是相Ⅱ结合反应中一种常见但相对次要的途径。在甲基化结合反应中，所使用的辅因子为S-腺苷甲硫氨酸（SAM）。SAM是继ATP之后第二广泛使用的酶底物，并在众多重要的生物过程中扮演着关键角色。SAM通过甲硫氨酸与ATP的反应合成，此过程由甲硫氨酸腺苷转移酶（MAT）催化。存在两个基因，MAT1A和MAT2A，它们分别编码两种同源的MAT催化亚基，即1型和2型。<br>在与其他亲核底物结合的过程中，SAM上连接至磺基阳离子的甲基基团被转移到底物上，形成结合物。失去甲基基团的SAM随后转化为S-腺苷高半胱氨酸（SAH）。SAH可以被水解生成腺苷和高半胱氨酸。高半胱氨酸可以转化为谷胱甘肽，或者甲基化形成甲硫氨酸，从而成为SAM合成的起点，并完成循环。<br>受攻击的官能团包括酚类、儿茶酚、脂肪族和芳香族胺以及含硫基团。催化甲基基团转移到这些官能团的酶为甲基转移酶（MT）。MTs是小型的、细胞质中的单聚酶，它们利用SAM作为甲基供体。虽然存在许多MTs，但研究最为深入的MTs是根据其典型的底物命名的：如<i><b>COMT</b>（儿茶酚-O-甲基转移酶）</i>、<i><b>TPMT</b>（硫嘌呤甲基转移酶）</i>、<i><b>TMT</b>（硫醇甲基转移酶）</i>、<i><b>HNMT</b>（组胺N-甲基转移酶）</i>和<i><b>NNMT</b>（烟酰胺N-甲基转移酶）</i>。以下是每种酶的例子。在每种情况下，均展示了该酶的典型底物。