Methionine adenosyltransferase

A sulfonium derivative, abbreviated AdoMet or SAM, that is primarily generated by the action of methionine adenosyltransferase (ATP + L-methionine + H2O SAM + Pi + pyrophosphate). SAM is a major methylat-... 

METHIONINE ADENOSYLTRANSFERASE METHIONINE y-LYASE METHIONINE SULFOXIDE REDUCTASE Methionine synthase,... 

METHIONINE ADENOSYLTRANSFERASE METHIONYL-tRNA SYNTHETASE NAD SYNTHETASE... 

Fig. 1. Ethylene biosynthesis. The numbered enzymes are (1) methionine adenosyltransferase, (2) ACC (l-aminocyclopropane-l-carboxylic acid) synthase, (3) ethylene forming enzyme (EFE), (4) 5 -methylthio-adenosine nucleosidase, (5) 5 -methylthioribose kinase. Regulation of the synthesis of ACC synthase and EFE are important steps in the control of ethylene production. ACC synthase requires pyridoxal phosphate and is inhibited by aminoethoxy vinyl glycine EFE requires 02 and is inhibited under anaerobic conditions. Synthesis of both ACC synthase and EFE is stimulated during ripening, senescence, abscission, following mechanical wounding, and treatment with auxins.

Pan, F. and Tarver, H. 1967. Comparative studies on methionine, selenomethionine and the ethyl analogues as substrates for methionine adenosyltransferase from rat liver. Arch. Biochem. Biophys. 119, 429-434. 

SAM) by methionine adenosyltransferase. SAM serves as a methyl donor for a variety of methyl acceptors, including DNA, protein, neurotransmit-ters, and phospholipids. 5-Adenosylhomocysteine (SAH) is produced following methyl donation by SAM, and homocysteine is formed through the liberation of adenosine from SAH by the enzyme SAH hydrolase. Unlike methionine and cysteine, homocysteine is not incorporated into polypeptide chains during protein synthesis. Instead, homocysteine has one of two metabolic fates transsulfuration or remethylation to methionine. 

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.

Figure 10.9. Metabolism of methionine. Methionine adenosyltransferase, EC 2.5.1.6 methionine synthetase, EC 2.1.1.13 (vitamin B12-dependent) and EC 2.1.1.5 (betaine as a methyl donor) cystathionine, 6-synthetase, EC 4.2.1.22 and y-cystathionase, EC 4.4.I.I.

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.)...

Deficiencies of methionine adenosyltransferase, cystathionine 8-synthase, and cystathionine )/-lyase have been described. The first leads to hypermethioninemia but no other clinical abnormality. The second leads to hypermethioninemia, hyperhomocysteinemia, and homo-cystinuria. The disorder is transmitted as an autosomal recessive trait. Its clinical manifestations may include skeletal abnormalities, mental retardation, ectopia lentis (lens dislocation), malar flush, and susceptibility to arterial and venous thromboembolism. Some patients show reduction in plasma methionine and homocysteine concentrations and in urinary homocysteine excretion after large doses of pyridoxine. Homocystinuria can also result from a deficiency of cobalamin (vitamin B12) or folate metabolism. The third, an autosomal recessive trait, leads to cystathioninuria and no other characteristic clinical abnormality. 

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. 

The only known reaction by which AdoMet is synthesized is that catalyzed by methionine adenosyltransferase (E.C. 2.5.1.6). 

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...

Fmkelstem J D, Kyle W E, and Martin J J (1975) Abnormal methionine adenosyltransferase in hypermethionmemia Biochem Biophys Res Commun 66, 1491-1497... 

Gaull G E. and Tallan H H. (1974) Methionine adenosyltransferase deficiency. New enzymatic defect associated with hypermethionmemia Science 186, 59-60... 

Gaull G E., Tallan H H, Lonsdale D., Przyrembel H, Schaffner F, and von Bassewitz D B. (1981b) Hypermethioninemia associated with methionine adenosyltransferase deficiency Clinical morphologic, and biochemical observations on four patients. /. Pedtat 98, 734-741... 

Tallan H. H. (1979) Methionine adenosyltransferase in man Evidence for multiple forms. Biochem Med 21, 129-140... 

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