Methionine metabolism

Methionine metabolism.

The first step in (L)-Methionine metabolism, the synthesis of S-Adenosyl-(L)-methionine, is catalyzed by the Methionine adenosyltransferase I, alpha (MAT1A) [1], [2], [3] and Methionine adenosyltransferase II, alpha (MAT2A) [2], [3], [4], [5], [6].

S-Adenosyl-(L)-methionine (AdoMet) is the primary methyl group donor in virtually all mammalian systems. DNA (cytosine-5-)-methyltransferase 1 (Dnmt1) [7], [8], DNA (cytosine-5-)-methyltransferase 3 alpha (DNMT3A) [9] and DNA (cytosine-5-)-methyltransferase 3 beta (DNMT3B) [9] naturally catalyze the transfer of the activated methyl group from AdoMet to C5 atom of DNA cytosine with formation of S-Adenosyl-(L)-homocysteine (AdoHcy).

S-adenosylhomocysteine hydrolase (SAHH) [10], [11], [12], S-adenosylhomocysteine hydrolase-like 1 (SAHH2) [13] and S-Adenosylhomocysteine hydrolase-like 2 (SAHH3) [13] catalyze the hydrolysis of AdoHcy to adenosine and (L)-Homocysteine. In turn, Cystathionine beta-synthase (CBS) catalyzes the condensation of (L)-Serine and (L)-Homocysteine to form (L)-Cystathionine [14], [15]. Cystathionase (cystathionine gamma-lyase) (CTH) catalyzes the second step in the reverse trans-sulfuration pathway (the cleavage of the (L)-Cystathionine C-gamma-S bond) yielding (L)-Cysteine, 2-Oxobutanoic acid, and ammonia [16].

(L)-Methionine, as another amino acid involved in protein biosynthesis, that forms aminoacyl-tRNA conjugated with corresponding tRNA by Methionyl-tRNA synthetase (MARS) [17], [18]. Mitochondrial (L)-Methionine*(tRNA) then undergoes formylation to N-Formyl-(L)-methionine*(tRNA) by Mitochondrial methionyl-tRNA formyltransferase (FMT) [19].

References:

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   S-adenosylmethionine synthesis: molecular mechanisms and clinical implications. Pharmacology & therapeutics 1997;73(3):265-80
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