甲基化
中文名称
通路描述
甲基化是相 II 结合反应中一种常见但次要的途径，与葡萄糖醛酸化或磺酸化相比。甲基化反应所需的辅因子是 S-腺苷甲硫氨酸（SAM）。SAM 是 ATP 之后第二广泛使用的酶底物，参与各种重要的生物学过程。SAM 由甲硫氨酸与 ATP 反应生成，由甲硫氨酸腺苷酰转移酶（MAT）催化。有两个基因，MAT1A 和 MAT2A，编码两个同源 MAT 催化亚基 1 和 2。在与亲核底物结合时，SAM 上连接在磺盐离子上的甲基基团转移到底物上形成共轭物。SAM 失去甲基基团后转化为 S-腺苷异硫氰酸（SAH）。SAH 可水解形成腺苷和半胱氨酸。半胱氨酸可以转化为谷胱甘肽或甲基化形成甲硫氨酸，从而形成 SAM 合成的起点并完成循环。攻击的功能基团包括酚类、儿茶酚类、脂肪族和芳香族胺以及含硫基团。催化将甲基基团转移至这些功能基团的酶是甲基转移酶（MT）。MT 是小的、胞质、单体酶，利用 SAM 作为甲基供体。有许多 MT，但研究最深入的以典型底物命名：COMT（儿茶酚 O-甲基转移酶）、TPMT（硫嘌呤甲基转移酶）、TMT（半胱氨酸甲基转移酶）、HNMT（组胺 N-甲基转移酶）和 NNMT（烟酰胺 N-甲基转移酶）。每种酶提到的例子及其典型底物如下。
英文描述
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.
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.
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: COMT (catechol O-methyltransferase), TPMT (thiopurine methyltransferase), TMT (thiol methyltransferase), HNMT (histamine N-methyltransferase) and NNMT (nicotinamide N-methyltransferase). An example of each enzyme mentioned is given. In each case, a typical substrate for the enzyme is shown.
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.
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: COMT (catechol O-methyltransferase), TPMT (thiopurine methyltransferase), TMT (thiol methyltransferase), HNMT (histamine N-methyltransferase) and NNMT (nicotinamide N-methyltransferase). An example of each enzyme mentioned is given. In each case, a typical substrate for the enzyme is shown.
所含基因
14 个基因