Methionine activated

Figure 30-17. Formation of S-adenosylmethionine. -CHj represents the high group transfer potential of "active methionine."...

Methionine. Methionine reacts with ATP forming 5-adenosylmethionine, active methionine (Figure 30-17). Subsequent reactions form propionyl-CoA (Figure 30-18) and ultimately succinyl-CoA (see Figure 19-2). 

S. Tokuyama and K. Hatano, Overexpression of the gene for N-acylamino add racemase from Amycolatopsis sp. TS-1-60 in Escherichia coli and continuous production of optically active methionine in a bio-reactor, Appl. Microbiol. Biotechnol. 1996, 44, 774-777. 

Fig. 1 GSH synthesis and methylation pathways in neuronal cells. Cysteine for GSH synthesis is provided by either uptake via EAAT3 or via transsulfuration of homocysteine (HCY), although transsulfuration is limited in neuronal cells, increasing the importance of uptake. Methionine synthase activity in neurons requires methylcobalamin (MeCbl), whose synthesis is GSH dependent. Dopamine-stimulated PLM is dependent upon methionine synthase activity. Methionine synthase activity determines levels of the methyl donor SAM and the methylation inhibitor SAH, affecting the efficiency of a large number of cellular methylation reactions.

Fig. 5 D4 dopamine receptor-mediated phospholipid methylation. Dopamine occupation of the D4 receptor initiates transfer of a methyl group (CH3) from an activated methionine residue to an adjacent phospholipid. A replacement methyl group is provided by methylfolate, via the action of methionine synthase...

Following peptide bond synthesis, the ribosome Is translocated along the mRNA a distance equal to one codon. This translocation step is promoted by hydrolysis of the GTP in eukaryotic EF2-GTP. As a result of translocation, tRNAj , now without its activated methionine, is moved to the E (exit) site on the ribosome concurrently, the second tRNA, now covalently bound to a dIpeptIde (a peptIdyl-tRNA), Is moved to the P site (Figure 4-26, step U). Translocation thus returns the ribosome conformation to a state in which the A site Is open and able to accept another amlnoacylated tRNA complexed with EFlct-GTP, beginning another cycle of chain elongation. 

K.L. Kiick, R. Weberskirch, D.A. Tirrell, Identification of an expanded set of translationally active methionine analogues in Escherichia coli, FEBS Lett. 2001, 502, 25-30. 

Each protein has, within this general pattern, its own characteristic radical distribution. In ribonuclease, lysine exhibits a much higher activity than do the remaining amino acids. Lysine and methionine are the most heavily labeled residues in lysozyme. In myoglobin, histidine has the highest activity. Methionine is the most heavily labeled amino acid in chymotrypsinogen, as is proline in insulin. Despite the similarities, therefore, each native protein exhibits a characteristic tritium distribution. 

This is the enzyme responsible for activating methionine to the 5-adenosyl form in which it acts as a methyl donor. It may be assayed radiochemically using C labelled methionine and product separation using ion exchange. 

S-Adenosyl-L-methionine, S-(S -ikaxyadenosme-5 )-methionme, active methionine, active methyl, SAM a reactive sulfonium compound (Fig.) (M, of free cation 398.4), and the most important methylating agent in cellular metabolism (see liansmethyla-tion). 

Ammo-3-carboxypropyl) methyl]-sulfonio]-5 -deoxyadenosine hydroxide inner salt, 9CI. S-Adenosylmethionine. Active methionine [2613-02-7]... 

S-Adenosyl-L-methionine ( activated methionine ) is a sulfonium compound, which possesses the reactive —group. 

S-Adenosylmethionine appears to be broken down in yeast to form thiomethyladenosine. This compound was shown by Schlenk to accumulate when methionine was fed to yeast and to contain the methyl carbon and the sulfur of the methionine, but it is not certain that the formation of thiomethyladenosine from active methionine is enzymatic. 

Homoserine also has been detected in filtrates of liver preparations incubated with methionine. Cantoni provisionally identified homoserine as a product of the acid hydrolysis of active methionine (S-adeno-sylmethionine). Beyond homoserine, the postulated reactions 2 and 3 are still more speculative. It might be presumed that homoserine is oxidized to aspartic acid, in analogy to the observations on the catabolism of lysine, in which the analogous a-amino adipic acid is an intermediate. If aspartic acid is formed, the subsequent reaction sequence is readily apparent. Evidence favorable to the proposed reaction pathway is the finding of Marshall and Friedberg, of the occurrence of a small amount of fumaric acid, labeled in the methine carbons, from the livers of mice injected with DL-methionine-2-C. ... 

Corroborative evidence has been obtained from experiments with isolated tissue preparations. The in vitro formation of cystine by liver slices (and a saline extract) was observed in nuxtures containing dl-homocysteine and DL-serine. Neither substance was effective when incubated alone. The L-forms of the two amino acids were implicated in the reaction, as D-homocysteine and o-serine did not substitute for the DL-forms and the isolated cystine had the L-configuration. The reaction proceeded best under anaerobic conditions and in the present of O.OOlAf CN , as the latter inhibits cysteine desulfhydrase activity. Methionine substituted very poorly for homocysteine in vitro. 

Because of its role in activating methionine for transmethylation, this enzyme was initially called the methionine-activating enzyme. With the later discovery of enzymes which activate the carboxyl group of methionine and other amino acids for protein synthesis, this term became somewhat confusing. In this chapter, the trivial name methionine adenosyltransferase or adenosyhransferase, will be used in accord with the recommendation of the Commission on Enzymes (Enzyme Nomenclature, American Elsevier, New York, 1965). The enzyme has also been called S-adenosylmethionine synthetase. 

Asparagine, methionine, lysine, threonine and isoleucine are derived from aspartate, which is issued from oxaloacetate. ATP can activate methionine to form 5-adenosyhnethionine, which can be demethylated to form S-adenosylhomocysteine, the hydrolysis of which liberates adenine to produce homocysteine. 

Adenosine triphosphate is the specific nucleotide of this reaction. Active methionine is the methyl donor to various acceptors, e.g., nicotinamide, glycocyamine, adrenaline. Transmethylations are catalyzed by specific methylpherases The product of transmethylation is usually the iV-methyl derivative of the acceptor while active methionine is converted to (S-adenosylhomocysteine. Active methionine may undergo hydrolytic cleavage in yeast to yield 5 -methylthioadenosine and homoserine 96). The reaction may not be enzymic. This adenosine derivative had been isolated long before active methionine was known 96). Betaine and certain sul-fonium compounds structurally related to active methionine, e.g., dimethyl-/8-propiothetin [(CHs)2= S—CH —CHj—COOH] 97), can also act as methyl donors for homocysteine in liver suspensions 98). 

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