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MetaCyc Pathway: L-methionine degradation I (to L-homocysteine)
Traceable author statement to experimental support

Enzyme View:

Pathway diagram: L-methionine degradation I (to L-homocysteine)

This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Superclasses: Degradation/Utilization/AssimilationAmino Acids DegradationProteinogenic Amino Acids DegradationL-methionine Degradation

Some taxa known to possess this pathway include : Rattus norvegicus, Saccharomyces cerevisiae

Expected Taxonomic Range: Archaea, Bacteria , Eukaryota

In the degradation pathway shown here, L-methionine is first metabolized to S-adenosyl-L-methionine (SAM), a compound that mediates most biological methylations. In the second reaction, the S-methyl group is transferred to other acceptors in a transmethylation step. The product, S-adenosyl-L-homocysteine, is then hydrolyzed to L-homocysteine and adenosine.

L-homocysteine is a branch point. In rats and humans approximately half of the homocysteine formed is remethylated back to methionine via two salvage pathways, one involving methionine synthase (EC, and the other involving betaine-homocysteine S-methyltransferase (EC (see L-methionine salvage from L-homocysteine).

The remainder of the homocysteine is degraded further. The first step is the condensation with serine to form L-cystathionine. cystathionine γ-lyase catalyzes cleavage of the C-γ-S bond of L-cystathionine, yielding L-cysteine, 2-oxobutanoate and ammonia in a transsulfuration reaction (see L-cysteine biosynthesis III (from L-homocysteine)) [Griffith87, Finkelstein90].

Superpathways: superpathway of L-methionine salvage and degradation, superpathway of L-cysteine biosynthesis (mammalian)

Variants: L-methionine degradation II, L-methionine degradation III

Created 15-Mar-1999 by Wagg J, SRI International
Revised 13-Sep-2006 by Caspi R, SRI International


Finkelstein90: Finkelstein JD (1990). "Methionine metabolism in mammals." J Nutr Biochem 1(5);228-37. PMID: 15539209

Griffith87: Griffith OW (1987). "Mammalian sulfur amino acid metabolism: an overview." Methods Enzymol 143;366-76. PMID: 3309559

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Bairoch93a: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Brzezinski01: Brzezinski K, Janowski R, Podkowinski J, Jaskolski M (2001). "Sequence determination and analysis of S-adenosyl-L-homocysteine hydrolase from yellow lupine (Lupinus luteus)." Acta Biochim Pol 48(2);477-83. PMID: 11732617

Cabrero87: Cabrero C, Puerta J, Alemany S (1987). "Purification and comparison of two forms of S-adenosyl-L-methionine synthetase from rat liver." Eur J Biochem 170(1-2);299-304. PMID: 3121322

Chattopadhyay91: Chattopadhyay MK, Ghosh AK, Sengupta S (1991). "Control of methionine biosynthesis in Escherichia coli K12: a closer study with analogue-resistant mutants." J Gen Microbiol 137(3);685-91. PMID: 2033383

Chiang77: Chiang PK, Cantoni GL (1977). "Activation of methionine for transmethylation. Purification of the S-adenosylmethionine synthetase of bakers' yeast and its separation into two forms." J Biol Chem 1977;252(13);4506-13. PMID: 194884

Chou72: Chou TC, Talalay P (1972). "The mechanism of S-adenosyl-L-methionine synthesis by purified preparations of bakers' yeast." Biochemistry 1972;11(6);1065-73. PMID: 4552214

Fujioka81: Fujioka M, Takata Y (1981). "S-Adenosylhomocysteine hydrolase from rat liver. Purification and some properties." J Biol Chem 256(4);1631-5. PMID: 7462216

Gomi85: Gomi T, Ishiguro Y, Fujioka M (1985). "S-Adenosylhomocysteinase from rat liver. Evidence for structurally identical and catalytically equivalent subunits." J Biol Chem 260(5);2789-93. PMID: 3972804

Gonzalez03: Gonzalez B, Pajares MA, Hermoso JA, Guillerm D, Guillerm G, Sanz-Aparicio J (2003). "Crystal structures of methionine adenosyltransferase complexed with substrates and products reveal the methionine-ATP recognition and give insights into the catalytic mechanism." J Mol Biol 331(2);407-16. PMID: 12888348

Greene73: Greene RC, Hunter JS, Coch EH (1973). "Properties of metK mutants of Escherichia coli K-12." J Bacteriol 115(1);57-67. PMID: 4577753

Guranowski77: Guranowski A, Pawelkiewicz J (1977). "Adenosylhomocysteinase from yellow lupin seeds. Purification and properties." Eur J Biochem 80(2);517-23. PMID: 923592

Hiroki97: Hiroki T, Horikawa S, Tsukada K (1997). "Structure of the rat methionine adenosyltransferase 2A gene and its promoter." Eur J Biochem 250(3);653-60. PMID: 9461287

Horikawa89: Horikawa S, Ishikawa M, Ozasa H, Tsukada K (1989). "Isolation of a cDNA encoding the rat liver S-adenosylmethionine synthetase." Eur J Biochem 184(3);497-501. PMID: 2806235

Hu99: Hu Y, Komoto J, Huang Y, Gomi T, Ogawa H, Takata Y, Fujioka M, Takusagawa F (1999). "Crystal structure of S-adenosylhomocysteine hydrolase from rat liver." Biochemistry 38(26);8323-33. PMID: 10387078

Kamarthapu08: Kamarthapu V, Rao KV, Srinivas PN, Reddy GB, Reddy VD (2008). "Structural and kinetic properties of Bacillus subtilis S-adenosylmethionine synthetase expressed in Escherichia coli." Biochim Biophys Acta 1784(12);1949-58. PMID: 18634909

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Lee97: Lee JH, Chae HS, Lee JH, Hwang B, Hahn KW, Kang BG, Kim WT (1997). "Structure and expression of two cDNAs encoding S-adenosyl-L-methionine synthetase of rice (Oryza sativa L.)." Biochim Biophys Acta 1354(1);13-8. PMID: 9375784

Markham80: Markham GD, Hafner EW, Tabor CW, Tabor H (1980). "S-Adenosylmethionine synthetase from Escherichia coli." J Biol Chem 1980;255(19);9082-92. PMID: 6251075

Markham81: Markham GD (1981). "Spatial proximity of two divalent metal ions at the active site of S-adenosylmethionine synthetase." J Biol Chem 1981;256(4);1903-9. PMID: 6257692

Showing only 20 references. To show more, press the button "Show all references".

Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.5 on Sat Apr 30, 2016, BIOCYC11A.