Methionine S-adenosyltransferase

SuFRiN, J.R., Dunn, D.A., Marshall, G.R. Steric mapping of the L-methionine binding site of ATP L-methionine S-adenosyltransferase. Mol. Pharmacol. 1981,19, 307-313. 

Fig. 2 Transulphuration pathway. Enzymes involved 1 methionine S-adenosyltransferase, Jmethyltransferase, 3 S-adenosylhomocysteine hydrolase, 4 cystathionine -synthase, 5 p-cys-tathionase, 6 methionine synthase...

The key steps in this pathway are the first one catalysed by methionine S-adenosyltransferase and the last one, which is irreversible, catalysed by j0-cystath-ionase. 

Enzymes catalyzing the formation of S-adenosylinethionine (i.e., ATP-L-methionine S-adenosyltransferase, EC 2.5.1.6) are widely dis-... 

Figure 21-1. Structural and metabolic relationships between methionine, homocysteine, and cysteine. CBS, cystathionine b-synthase CTH, cystathionine y-lyase MAT, methionine adenosyltransferase MS, methionine synthase 5-MTHF, 5-methyltetrahydrofoIate MTs, methyl transferases PLR pyridoxal phosphate SAH, S-adenosylhomocysteine SAHH, SAH hydrolase THF, tetrahydrofolate.

Protection required. Suppose that a mutation in bacteria resulted in diminished activity of methionine adenosyltransferase, the enzyme responsible for the synthesis of SAM from methionine and ATP. Predict how this might affect the stability of the mutated bacteria s DNA. 

Figure 8 Extended folate metabolism, including compartmentation. MTHFR, methylenetetrahydrofolate reductase SHMT, serine hydroxymethyltransferase BHMT, betaine homocysteine methyltransferase, MAT, methionine adenosyltransferase SAH-hydrolase, S-adenosylhomocysteine hydrolase MT, methyltransferase CBS, cystathionine /i-synthase SAM, S-adenosylmethionine SAH, S-aden-osylhomocysteine THF, tetrahydrofolate and 5-MeTHF, 5-methyltetrahydrofolate. (Reproduced from Van der Put etal. (2001) Folate, homocysteine and neural tube defects An overview. Experimental Biology and Medicine 226 243-270.)...

S-Adenosyl methionine An important carrier of activated methyl groups. It is formed by the condensation of ATP with the amino acid methionine catalyzed by the enzyme methionine adenosyltransferase in a reaction that releases triphosphate. 

In the continuing search for isozyme-specific inhibitors of rat methionine adenosyltransferases, the covalent conjugate (119) of L-ethionine and adenylyl imidodiphosphate has been prepared. 23 in the synthetic route, protected adenosine was converted to its 5 -aldehyde, condensed with vinylmagnesium bromide, and hydroboration, tosylation and condensation with L-homocysteinate served to introduce the L-ethionine moiety, the 5 -hydroxy group then being phosphorylated by Tener s method and converted conventionally to the p, y-imidotriphosphate. 

Drummelsmith J, Girard I, Trudel N et al. Difierential protein expression analysis c Leishmania major reveals novel roles for methionine adenosyltransferase and S-adenosylmethionine in methotrexate resistance. J Bioi Chem 2004 279(32) 33273-80. 

These combined findings indicate that chloroplasts catalyze the conversion of aspartate to cystathionine, although it is not known to what extent these reactions may also be catalyzed by extrachloroplastic fractions. The subcellular site(s) for further metabolism by cystathionine-j8-Iyase, tetrahy-dropteroyltriglutamate methyltransferase and methionine adenosyltransferase is not clear, although an appreciable percentage of the total tetrahydro-pteroyltriglutamate methyltransferase can reside in mitochondria. Further studies are obviously required to establish the quantitative interrelationship of chloroplasts and other subcellular sites in the de novo-synthesis of methionine and AdoMet. 

Fig. 20.3 Pathway of methionine metabolism. The numbers represent the following enzymes or sequences (1) methionine adenosyltransferase (2) S-adenosylmethionine-dependent transmethylation reactions (3) glycine methyltransferase (4) S-adenosylhomocysteine hydrolase (5) betaine-homocysteine methyltransferase (6) 5-methyltetrahydrofolate homocysteine methyltransferase (7) serine hydroxymethyltransferase (8) 5,10-methylenetetrahydrofolate reductase (9) S-adenosylmethionine decarboxylase (10) spermidine and spermine synthases (11) methylthio-adenosine phosphorylase (12) conversion of methylthioribose to methionine (13) cystathionine P-synthase (14) cystathionine y-lyase (15) cysteine dioxygenase (16) cysteine suplhinate decarboxylase (17) hypotaurine NAD oxidoreductase (18) cysteine sulphintite a-oxoglutarate aminotransferase (19) sulfine oxidase. MeCbl = methylcobalamin PLP = pyridoxal phosphate...

Fig. 24. Synthesis and transformation of S-adenosyl-L-methionine 1 Methionine adenosyltransferase 2 methyltransferase...

Methionine adenosyltransferase 2 S-adenosylmethionine-dependent methyltransferases 3 1-aminocyclopropanecarboxylic acid (ACC) synthetase 4 oxygenase... 

The biosynthesis of SAM 1 is catalyzed by S-adenosyhnethionine synthetase (also called methionine adenosyltransferase, MTA), where c-Met 7 and adenine triphosphate (ATP) are substrates to result in SAM and inorganic phosphate (Pj) and inorganic pyrophosphate (PPj) (Scheme 18.5, pathway i). The hydrolysis of the... 

Hu, H., Qian, )., Chu, J., Wang, Y., Zhuang, Y., and Zhang, J. (2009) Optimization of L-methionine feeding strategy for improving S-adenosyl-L-methionine production by methionine adenosyltransferase overexpressed Pichia pastoris. Appl Microbiol Biotechnol., 83, 1105-1114. 

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. 

Parry RJ, Minta A. Studies of enzyme stereochemistry-elucidation of the stereochemistry of S-adenosylmethionine formation by yeast methionine adenosyltransferase. J. Am. Chem. Soc. 1982 104 871-872. 

Lu, S.C., Alvarez, L., Huang, Z.-Z., Chen, L., An, W., Corrales, F.J., AvUa, M.T., Kanel, G., and Mato, JM. (2002). Methionine adenosyltransferase 1A knockout mice are predisposed to liver injury and exhibit increased expression of genes involved in proliferation. Proc. Natl. Acad. Sci. USA 98,5560-5565. 

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