Methionine S-methyl

The location of methionine incorporation into peptide chains by enzymatic modification was also investigated using L-methionine-S-methyl14C methyl ester hydrochloride and L-3Hmethionine ethyl ester hydrochloride [104]. Substrates of the enzymatic modification used were a tryptic hydrolysate of serum albumin and an a-chymotryptic hydrolysate of casein, a-chymotrypsin was used as catalyst during the EPM reactions. Part of the L-methionine-S-methyl 14C methyl ester was incorporated as Met into peptide chains. A maximum curve... 

Isotopic studies with labeled potential precursors such as sodium acetate- " C, threonine- C, histidine- " C, histidinol- " C, and L-methionine-(S-methyl- " C) were carried out with P. pennatifolius in an attempt to prove the proposed pathways [8, 39]. Only the methylation of pilocarpidine, last step in both mechanisms, was attested by significant incorporation of radioactivity in the methyl group attached to the imidazole nucleus. This data confirmed an important assumption, the one that considers methionine the biological source of the A -methyl group of pilocarpine. Also, one should consider that these radiolabeled studies were carried out with stems, no other parts of the plant were analyzed, and thus some other site involved in biosynthesis was not considered in this study. 

Methicillin — see Penicillin, 2,6-dimethoxyphenyl-Methidathion insecticidal activity, 6, 576 as insecticide, 1, 196 Methine, dipteridyl-synthesis, 3, 303 Methine dyes, 1, 323-325, 332 L-Methionine, S-adenosyl-in metabolic iV-methylation, 1, 236 Methionine, dehydro- C NMR, 6, 139 X-ray crystallography, 6, 136 Methiothepin... 

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. 

In addition to bacterial conversion of L-methionine to cheese aroma compounds, certain cheese-ripening yeasts have been implicated. They include De-baromyces hansenii, Geotrichum candidum, and Yarrowia lipolytica, in addition to Kluyveromyces lactis and Saccharomyces cerevisiae (previously noted). Of these yeasts, Geotrichum candidum was most effective at producing sulfur compounds with the major product being S-methyl thioacetate, with smaller amounts of MT, DMS, DMDS, and DMTS. Kluyveromyces lactis had a similar profile, but produced a much smaller amount of S-methyl thioacetate than did G. candidum. S-Methyl thioacetate is formed by a reaction of MT and acetyl-CoA (Equation 7) ... 

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. 

SMM synthesis is mediated by the enzyme methionine S-methyltransferase (MMT) through the essentially irreversible, AdoMet-mediated methylation of methionine.48"5 Both MMT and SMM are unique to plants 48,50 The opposite reaction, in which SMM is used to methylate homocysteine to yield two molecules of methionine, is catalyzed by the enzyme homocysteine S-methyltransferase (HMT).48 Unlike MMT, HMTs also occur in bacteria, yeast, and mammals, enabling them to catabolize SMM of plant origin, and providing an alternative to the methionine synthase reaction as a means to methylate homocysteine. Plant MMT and HMT reactions, together with those catalyzed by AdoMet synthetase and AdoHcy hydrolase, constitute the SMM cycle (Fig. 2.4).4... 

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. ... 

The most common posttranslational modifications, discussed in the following sections, include phosphorylation, sulfation, disulfide formation, N-methylation, O-methylation, S-methylation, N-acetylation, hydroxylation, glycosylation, ADP-ribosylation, prenylation, biotinylation, lipoylation, and phosphopan-tetheine tethering. Many of the posttranslational modifications are proven to be cross talks. Other modifications exist in a smaller extent and include oxidation of methionine, C-methylation, ubiquitylation, carboxylation, and amidation. These topics will not be covered in this chapter which is meant to focus primarily on the recent literature (2005-08). For a more complete coverage of all posttranslational modifications and earlier literature (up to 2005), the reader is referred to Professor Christopher T. Walsh s book Posttranslational Modification of Proteins Expanding Nature s Inventory ... 

The anaemia in B deficiency is caused by an inability to produce sufficient of the methylating agent S-adenosyhnethionine. This is required by proliferating cells for methyl group transfer, needed for synthesis of the deoxythymidine nucleotide for DNA synthesis (see below and Chapter 20). This leads to failure of the development of the nucleus in the precursor cells for erythrocytes. The neuropathy, which affects peripheral nerves as well as those in the brain, is probably due to lack of methionine for methyl transfer to form choline from ethanolamine, which is required for synthesis of phosphoglycerides and sphingomyelin which are required for formation of myelin and cell membranes. Hence, the neuropathy results from a... 

Figure 15.5 Four reactions involved in methylatlon. The reactions are (1) formation of S-adenosylmethlonIne (SAM) (11) transfer of methyl group to an acceptor (111) conversion of S-adenosylmethlonIne to homocysteine (Iv) conversion of homocysteine to methionine using methyl tetrahydrofolate as the methyl donor with the formation of FH4.

This enzyme [EC 1.8.4.5], also known as methionine S-oxide reductase, catalyzes the reaction of L-methionine with oxidized thioredoxin to produce L-methionine S-oxide and reduced thioredoxin. Dithiothreitol can substitute for reduced thioredoxin in the reverse reaction. In addition, other methyl sulfoxides can replace methionine sulfoxide in the reverse reaction. 

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. ... 

Lee, E. S., Chen, H., Hardman, C., Simm, A., and Charlton, C. (2008). Excessive S-adenosyl-1-methionine-dependent methylation increases levels of methanol, formaldehyde and formic add in rat brain striatal homogenates Possible role in S-adenosyl-l-methionone-induced Parkinsons s disease-like disorders. Life Sci. 83, 821-827. 

The Other enzyme in catecholamine catabolism is catecholamine 0-methyltransferase (COMT), a cytoplasmic enzyme that uses S-adenosyl-methionine to methylate the 3-OH of catecholamines and render them inactive. The methylated compounds are not taken up into the synapse. 

Although the most generally useful heterocycles for the alkylation of simple amino acids by this method are the imidazolidinones84, oxazolidinones have the advantage of being much more readily hydrolyzed. (S)-a-Methylmethionine was prepared by this latter method from the parent amino acid 85,86. The oxazolidinone 1885 [mp 126.4-127.2 °C [a]D +61.8 (e = 1, CHC13)] prepared in 24-30% yield from (S)-methionine, was methylated using LDA and iodomethane in satisfactory yield. 

TGN represents the sum of 6-thioguanosine monophosphate (6-thio-GMP), -diphosphate (6-thio-GDP) and -triphosphate (6-thio-GTP). In contrast, both TPMT and XO are the predominant catabolic enzymes in the metabolism of thiopurines. TPMT catalyses the X-adenosyl-L-methionine dependent S-methylation of 6-MP and its metabolites into 6-methyl-mercaptopurine (6-MMP), 6-methyl-mercaptopurine ribonucleotides (6-MMPR) such as 6-methylthioinosine monophosphat (meTIMP), and 6-methyl-thioguanine nucleotides (6-MTGN) (93). 

Figure 7.64 The role of methionine in methylation reactions and the mechanisms underlying ethionine hepatotoxic-r. ity. After the substrate is methylated, the S-adenosyl homocysteine remaining is broken down into homocysteine and adenine, both of which are reused. When S-adenosyl ethionine is formed, however, this recycling is reduced (=), and a shortage of adenine and hence ATP develops.

Another example of leaving group activation is the utilization of S-adenosyl-methionine rather than methionine in methylation reactions. A relatively basic thiolate anion has to be expelled from methionine, while the nonbasic neutral sulfur is displaced from the activated derivative (equation 2.68) ... 

Biosynthesis. The terminal C methyl of the propyl side chain, the S-methyl. and the /V methyl groups are derived from methionine, trans-4-Propyl-L-proline was shown to accumulate when Strepromyces lincolnensis is grown in media deficient in sulfur, and the addition of T. tyrosine or L-dihydroxyphenylalaiiine (DOPA) was shown to stimulate this production. 

One recent related study has been reported, tying together isomescaline and schizophrenia. Through the use of radioactive labelling, the extent of de-methylation (the metabolic removal of the methyl groups from the methoxyls) was determined in both schizophrenic patients and normal subjects. When there was a loading of the person with methionine (an amino acid that is the principal source of the body s methyl groups), the schizophrenics appeared to show a lesser amount of demethylation. 

The methyl-branch is introduced at the C-3 position of tautomer 11 of the keton 9 by an electrophilic.attack with active methione (S-methyl-5 -adenosyl methionine). Thus the 2,6-dideoxy-4-keto-3-C-methyl-D-ery//iro glycoside 12 results which after reduction furnishes, e.g., D-mycarose (cf. also Ref. [5]). 

A large number of both endogenous and exogenous compounds can be methylated by several N-, 0-, and S-methyl transferases. The most common methyl donor is S-adenosyl methionine (SAM), which is formed from methionine and ATP. Even though these reactions may involve a decrease in water solubility, they are generally detoxication reactions. Examples of biologic methylation reactions are seen in Figure 7.18. 

Plants S-methyl methionine 0.1 N HC1 in 70% C2H5OH Automated amino analyser [224]... 

DMS is formed during the biodegradation of organic sulfur compounds and by the biological methylation of sulfide and methanethiol. Precursors of DMS are methionine, S-methylmethionine, dimethylsulfoniopropionate (DMSP), dimethylsulfonioacetate (DMSA), dimethyl sulfoxide (DMSO), methionine sulfoxide and sulfone, trimethylsulfonium salts, S-methylcysteine, homocysteine, dimethyl disulfide (DMDS), 2-keto-4-methiolbutyrate, and 2-mercaptoacetate (thioglycollate). 

Methionine and its S-methyl derivative, S-methylmethionine, are probably important precursors of DMS in terrestrial regions. However, plants also produce a variety of nonprotein sulfur amino adds such as S-methylcysteine, its 7-glutamyl and sulfoxide derivatives, and djenkolic add (44). The biosyntheses and functions of these compounds are poorly understood, and mechanisms for their biodegradation may be of more than academic interest, particularly with respect to the generation of volatile sulfur compounds. 

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