Methylation

Authored: Jassal, B, 2005-02-03 14:13:47 Edited: Jassal, B, 2008-05-19 12:57:01 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.

http://purl.obolibrary.org/obo/HINO_0016335

Authored: Jassal, B, 2005-02-03 14:13:47

Edited: Jassal, B, 2008-05-19 12:57:01

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.

Reactome, http://www.reactome.org

Pubmed15130560

Pubmed10331075

Pubmed10898761

Methylation

http://purl.obolibrary.org/obo/NCBITaxon_9606

HINO:0016335

Methylation

ReactomeREACT_6946

GENE ONTOLOGYGO:0032259

Reactome Database ID Release 43156581

http://purl.obolibrary.org/obo/INO_0000021

http://purl.obolibrary.org/obo/HINO_0025109

http://purl.obolibrary.org/obo/HINO_0025108

http://purl.obolibrary.org/obo/HINO_0024196

http://purl.obolibrary.org/obo/HINO_0024194

http://purl.obolibrary.org/obo/HINO_0024232

http://purl.obolibrary.org/obo/HINO_0025111

http://purl.obolibrary.org/obo/HINO_0025113

http://purl.obolibrary.org/obo/HINO_0025110