Methionine metabolism

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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:

  1. Horikawa S, Tsukada K
    Molecular cloning and nucleotide sequence of cDNA encoding the human liver S-adenosylmethionine synthetase. Biochemistry international 1991 Sep;25(1):81-90
  2. Sullivan DM, Hoffman JL
    Fractionation and kinetic properties of rat liver and kidney methionine adenosyltransferase isozymes. Biochemistry 1983 Mar 29;22(7):1636-41
  3. Mato JM, Alvarez L, Ortiz P, Pajares MA
    S-adenosylmethionine synthesis: molecular mechanisms and clinical implications. Pharmacology & therapeutics 1997;73(3):265-80
  4. Horikawa S, Tsukada K
    Molecular cloning and developmental expression of a human kidney S-adenosylmethionine synthetase. FEBS letters 1992 Nov 2;312(1):37-41
  5. Okada G, Teraoka H, Tsukada K
    Multiple species of mammalian S-adenosylmethionine synthetase. Partial purification and characterization. Biochemistry 1981 Feb 17;20(4):934-40
  6. Panayiotidis MI, Stabler SP, Ahmad A, Pappa A, Legros LH Jr, Hernandez-Saavedra D, Schneider BK, Allen RH, Vasiliou V, McCord JM, Kotb M, White CW
    Activation of a novel isoform of methionine adenosyl transferase 2A and increased S-adenosylmethionine turnover in lung epithelial cells exposed to hyperoxia. Free radical biology & medicine 2006 Jan 15;40(2):348-58
  7. Pradhan S, Bacolla A, Wells RD, Roberts RJ
    Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. The Journal of biological chemistry 1999 Nov 12;274(46):33002-10
  8. Svedruzic ZM, Reich NO
    DNA cytosine C5 methyltransferase Dnmt1: catalysis-dependent release of allosteric inhibition. Biochemistry 2005 Jul 12;44(27):9472-85
  9. Aoki A, Suetake I, Miyagawa J, Fujio T, Chijiwa T, Sasaki H, Tajima S
    Enzymatic properties of de novo-type mouse DNA (cytosine-5) methyltransferases. Nucleic acids research 2001 Sep 1;29(17):3506-12
  10. Palmer JL, Abeles RH
    The mechanism of action of S-adenosylhomocysteinase. The Journal of biological chemistry 1979 Feb 25;254(4):1217-26
  11. Hershfield MS, Aiyar VN, Premakumar R, Small WC
    S-Adenosylhomocysteine hydrolase from human placenta. Affinity purification and characterization. The Biochemical journal 1985 Aug 15;230(1):43-52
  12. Ueland PM, Helland S
    S-adenosylhomocysteinase from mouse liver. Catalytic properties at cellular enzyme level. The Journal of biological chemistry 1980 Aug 25;255(16):7722-7
  13. Fumic K, Beluzic R, Cuk M, Pavkov T, Kloor D, Baric I, Mijic I, Vugrek O
    Functional analysis of human S-adenosylhomocysteine hydrolase isoforms SAHH-2 and SAHH-3. European journal of human genetics : EJHG 2007 Mar;15(3):347-51
  14. Kraus J, Packman S, Fowler B, Rosenberg LE
    Purification and properties of cystathionine beta-synthase from human liver. Evidence for identical subunits. The Journal of biological chemistry 1978 Sep 25;253(18):6523-8
  15. Kraus JP
    Cystathionine beta-synthase (human). Methods in enzymology 1987;143:388-94
  16. Steegborn C, Clausen T, Sondermann P, Jacob U, Worbs M, Marinkovic S, Huber R, Wahl MC
    Kinetics and inhibition of recombinant human cystathionine gamma-lyase. Toward the rational control of transsulfuration. The Journal of biological chemistry 1999 Apr 30;274(18):12675-84
  17. Dickman SR, Boll DJ
    Differential purification of methionine-tRNA synthetase and lysine-tRNA synthetase from rabbit liver. Biochemical and biophysical research communications 1977 Oct 24;78(4):1191-7
  18. Deniziak MA, Barciszewski J
    Methionyl-tRNA synthetase. Acta biochimica Polonica 2001;48(2):337-50
  19. Takeuchi N, Kawakami M, Omori A, Ueda T, Spremulli LL, Watanabe K
    Mammalian mitochondrial methionyl-tRNA transformylase from bovine liver. Purification, characterization, and gene structure. The Journal of biological chemistry 1998 Jun 12;273(24):15085-90

  1. Horikawa S, Tsukada K
    Molecular cloning and nucleotide sequence of cDNA encoding the human liver S-adenosylmethionine synthetase. Biochemistry international 1991 Sep;25(1):81-90
  2. Sullivan DM, Hoffman JL
    Fractionation and kinetic properties of rat liver and kidney methionine adenosyltransferase isozymes. Biochemistry 1983 Mar 29;22(7):1636-41
  3. Mato JM, Alvarez L, Ortiz P, Pajares MA
    S-adenosylmethionine synthesis: molecular mechanisms and clinical implications. Pharmacology & therapeutics 1997;73(3):265-80
  4. Horikawa S, Tsukada K
    Molecular cloning and developmental expression of a human kidney S-adenosylmethionine synthetase. FEBS letters 1992 Nov 2;312(1):37-41
  5. Okada G, Teraoka H, Tsukada K
    Multiple species of mammalian S-adenosylmethionine synthetase. Partial purification and characterization. Biochemistry 1981 Feb 17;20(4):934-40
  6. Panayiotidis MI, Stabler SP, Ahmad A, Pappa A, Legros LH Jr, Hernandez-Saavedra D, Schneider BK, Allen RH, Vasiliou V, McCord JM, Kotb M, White CW
    Activation of a novel isoform of methionine adenosyl transferase 2A and increased S-adenosylmethionine turnover in lung epithelial cells exposed to hyperoxia. Free radical biology & medicine 2006 Jan 15;40(2):348-58
  7. Pradhan S, Bacolla A, Wells RD, Roberts RJ
    Recombinant human DNA (cytosine-5) methyltransferase. I. Expression, purification, and comparison of de novo and maintenance methylation. The Journal of biological chemistry 1999 Nov 12;274(46):33002-10
  8. Svedruzic ZM, Reich NO
    DNA cytosine C5 methyltransferase Dnmt1: catalysis-dependent release of allosteric inhibition. Biochemistry 2005 Jul 12;44(27):9472-85
  9. Aoki A, Suetake I, Miyagawa J, Fujio T, Chijiwa T, Sasaki H, Tajima S
    Enzymatic properties of de novo-type mouse DNA (cytosine-5) methyltransferases. Nucleic acids research 2001 Sep 1;29(17):3506-12
  10. Palmer JL, Abeles RH
    The mechanism of action of S-adenosylhomocysteinase. The Journal of biological chemistry 1979 Feb 25;254(4):1217-26
  11. Hershfield MS, Aiyar VN, Premakumar R, Small WC
    S-Adenosylhomocysteine hydrolase from human placenta. Affinity purification and characterization. The Biochemical journal 1985 Aug 15;230(1):43-52
  12. Ueland PM, Helland S
    S-adenosylhomocysteinase from mouse liver. Catalytic properties at cellular enzyme level. The Journal of biological chemistry 1980 Aug 25;255(16):7722-7
  13. Fumic K, Beluzic R, Cuk M, Pavkov T, Kloor D, Baric I, Mijic I, Vugrek O
    Functional analysis of human S-adenosylhomocysteine hydrolase isoforms SAHH-2 and SAHH-3. European journal of human genetics : EJHG 2007 Mar;15(3):347-51
  14. Kraus J, Packman S, Fowler B, Rosenberg LE
    Purification and properties of cystathionine beta-synthase from human liver. Evidence for identical subunits. The Journal of biological chemistry 1978 Sep 25;253(18):6523-8
  15. Kraus JP
    Cystathionine beta-synthase (human). Methods in enzymology 1987;143:388-94
  16. Steegborn C, Clausen T, Sondermann P, Jacob U, Worbs M, Marinkovic S, Huber R, Wahl MC
    Kinetics and inhibition of recombinant human cystathionine gamma-lyase. Toward the rational control of transsulfuration. The Journal of biological chemistry 1999 Apr 30;274(18):12675-84
  17. Dickman SR, Boll DJ
    Differential purification of methionine-tRNA synthetase and lysine-tRNA synthetase from rabbit liver. Biochemical and biophysical research communications 1977 Oct 24;78(4):1191-7
  18. Deniziak MA, Barciszewski J
    Methionyl-tRNA synthetase. Acta biochimica Polonica 2001;48(2):337-50
  19. Takeuchi N, Kawakami M, Omori A, Ueda T, Spremulli LL, Watanabe K
    Mammalian mitochondrial methionyl-tRNA transformylase from bovine liver. Purification, characterization, and gene structure. The Journal of biological chemistry 1998 Jun 12;273(24):15085-90

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