S-Methyl-L-methionine

S-Methyl-L-methionine chloride (Vitamin U) [1115-84-0] M 199.5, [a]p +33 (0.2M pK[ 1.9, pKj 7.9. Likely impurities are methionine, methionine sulfoxide and methionine sulfone. from water by adding a large excess of EtOH. Stored in a cool, dry place, protected from light. 

Two compounds other than the natural substrate SAM, l-VG and S -methyl-L-methionine (SMM), have been described so far as both substrates and inhibitors of ACS isozymes. l-VG was isolated 30 years ago from the fungus Rhodophyllus nidorosus It was shown to be a mechanism-based inhibitor of aspartate aminotransferase and kynurenine aminotransferase. First of all, l-VG is an alternative substrate of ACS in addition to being an inhibitor as described in the previous section. ... 

Only four naturally occurring sulfonium salts are known. Two examples are dimethyl-p-propiothetin (8) and S-methyl-L-methionine (9) (Figure 2). Propiothetin (8) occurs in algae, plankton, fish and molluscs, and S-methyl-L-methionine (9) in cabbage, celery and other vegetables. 

S-Methyl-L-methionine chloride See Vitamin U in Miscellaneous Compounds , this chapter. 

Methionine in plants can be converted to the sulfonium compound S-methyl-L-methionine, also called vitamin U. It has strong osmoprotectant activity and accumulates in many marine algae and some flowering plants.Other organisms, including mammals, can use S-methylmethionine to methylate homocysteine, converting both reactants back to methionine enabling animals to meet some of their methionine need from this source. 

The monochiral S-methyl-L-methionine (1) contains pro-chiral, diastereotopic methyl groups which must, in principle, be transferable to a chiral or achiral acceptor molecule with different rates. An exploratory study, recently conducted in our... 

Catechol O-methyltransferase (COMT) is a widespread enzyme that catalyzes the transfer of the methyl group of S-adenosyl-l-methionine (AdoMet) to one of the phenolic group of the catechol substrate (Fig. 1). High COMT activity is found in the liver, kidney and gut wall... 

S-adenosyl-L-methionine (AdoMet, SAM) is a cofactor and the most important donor of the methyl (CH3-) group for methyltransferases, including COMT. When the methyl-group has been transferred, the remaining demethylated compound is called S-adenosyl-L-homo-cysteine. 

Esterification of the propionic acid side chain at C-13 (ring C) with a methyl group catalyzed by S-adenosyl-L-methionine-magnesium protoporphyrin 0-meth-yltransferase yields protoporphyrin IX monomethyl ester (MPE), which originates protochlorophyllide by a P-oxidation and cyclization of the methylated propionic side chain. This molecule contains a fifth isocyclic ring (ring E), the cyclopentanone ring that characterizes aU chlorophylls. 

Kauss, H., Swanson, A.L., and Hassid, W.Z. (1967) Biosynthesis of the methyl ester groups of pectin by transmethylation from S-adenosyl-L-methionine. Biochem.BiophysJies.Commun. 26 234-240. 

As already noted, MT has several sources such as lyase enzymes for L-methionine and S -methyl-L-cysteine. There are complex relationships between DMS, MT, and other VOSCs in the atmosphere, and in marine and terrestrial environments. The previously cited reviews should be consulted. 

The methyltransferases represent a relatively large number of enzymes that utilize the cofactor, S-adenosyl-L-methionine, in which the methyl group is bound to a positively charged sulfur, to transfer a methyl group to an oxygen, sulfur, or nitrogen atom in an appropriate substrate as shown in Figure 7.9 (8). 

In multicellular eukaryotes, DNA methylation is associated with transcriptional silencing [3]. In these organisms, DNA methylation has been observed exclusively on the C5 position of the cytosine ring and is frequently found in CpG-rich regions. This process is attributed to the action of DNA methyltransferases (DNMTs), which utilize the cofactor, S-adenosyl-L-methionine. Approximately half of all human genes have CpG islands in their promoter regions but these stretches of DNA are typically... 

Figure 13.1 (a) Trimethyllysine 4 and dimethylarginine 2 at histone H3 from X-ray structure [4]. (b) Chemical structure of the methylating agent S-adenosyl-L-methionine. 

This enzyme [EC 2.1.1.72] catalyzes the reaction of S-adenosyl-L-methionine with an adenine residue in DNA to produce S-adenosyl-L-homocysteine and a 6-methyl-aminopurine residue in DNA. 

Methyltransferases that utilize S-adenosyl-L-methionine as the methyl donor (and thus generating S-adenosyl-L-homocysteine) catalyze (a) A-methylation (e.g., norepinephrine methyltransferase, histamine methyltransferase, glycine methyltransferase, and DNA-(adenine-A ) methyltransferase), (b) O-methylation (e.g., acetylsero-tonin methyltransferase, catechol methyltransferase, and tRNA-(guanosine-0 ) methyltransferase), (c) S-methyl-ation (e.g., thiopurine methyltransferase and methionine S-methyltransferase), (d) C-methylation (eg., DNA-(cy-tosine-5) methyltransferase and indolepyruvate methyltransferase), and even (e) Co(II)-methylation during the course of the reaction catalyzed by methionine syn-thase. ... 

Enzymatic O-methylation of flavonoids, which is catalyzed by O-methyltransferases (E.C. 2.1.1.6-) involves the transfer of the methyl group of an activated methyl donor, S -adenosyl-L-methionine, to the hydroxyl group of a flavonoid acceptor with the formation of the corresponding methylether and S -adenosyl-L-homocysteine. The latter product is, in... 

The methyl transferases (MTs) catalyze the methyl conjugation of a number of small molecules, such as drugs, hormones, and neurotransmitters, but they are also responsible for the methylation of such macromolecules as proteins, RNA, and DNA. A representative reaction of this type is shown in Figure 4.1. Most of the MTs use S-adenosyl-L-methionine (SAM) as the methyl donor, and this compound is now being used as a dietary supplement for the treatment of various conditions. Methylations typically occur at oxygen, nitrogen, or sulfur atoms on a molecule. For example, catechol-O-methyltransferase (COMT) is responsible for the biotransformation of catecholamine neurotransmitters such as dopamine and norepinephrine. A-methylation is a well established pathway for the metabolism of neurotransmitters, such as conversion of norepinephrine to epinephrine and methylation of nicotinamide and histamine. Possibly the most clinically relevant example of MT activity involves 5-methylation by the enzyme thiopurine me thy Itransf erase (TPMT). Patients who are low or lacking in TPMT (i.e., are polymorphic) are at... 

S-Adenosyl-l-methionine (SAMe) is a naturally occurring substance whose primary role appears to be that of a methyl donor in the CNS ( 252). It participates in the metabolism of various biogenic amines implicated in the pathogenesis of depressive disorders. Several investigations have indicated that it may be an effective antidepressant with minimal adverse effects. 

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