Reverse methionine biosynthesis from S-adenosylmethionine in eukaryotic cells.
The intracellular ratio between methionine and its activated form S-adenosylmethionine (AdoMet) is of crucial importance for the one-carbon metabolism. AdoMet recycling into methionine was believed to be largely achieved through the methyl and the thiomethyladenosine cycles. We show here that in yeast, AdoMet recycling actually occurs mainly through the direct AdoMet-dependent remethylation of homocysteine. Compelling evidences supporting this result were obtained owing to the identification and functional characterization of two new genes, SAM4 and MHT1, that encode the yeast AdoMet-homocysteine methyltransferase and S-methylmethionine-homocysteine methyltransferase, respectively. Homologs of the Sam4 and Mht1 proteins exist in other eucaryotes, indicating that such enzymes would be universal and not restricted to the bacterial or fungal kingdoms. New pathways for AdoMet or S-methylmethionine-dependent methionine synthesis are presented.
Thomas
D
D
Centre de Génétique Moléculaire, CNRS 91 198 Gif-sur-Yvette, France.
Becker
A
A
Surdin-Kerjan
Y
Y
D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000502:physiology; D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D003839:Deoxyadenosines / Q000378:metabolism; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics; D005786:Gene Expression Regulation; D050904:Homocysteine S-Methyltransferase / Q000502:physiology; D008565:Membrane Proteins; D008715:Methionine / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D012436:S-Adenosylmethionine / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology; D013872:Thionucleosides / Q000378:metabolism; D014805:Vitamin B 12 / Q000494:pharmacology; D014814:Vitamin U / Q000378:metabolism; D015003:Yeasts / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D003839:Deoxyadenosines; D005656:Fungal Proteins; C118806:MTH1 protein, S cerevisiae; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D013872:Thionucleosides; D014814:Vitamin U; C008500:5'-methylthioadenosine; D012436:S-Adenosylmethionine; D008715:Methionine; D050904:Homocysteine S-Methyltransferase; C519167:MHT1 protein, S cerevisiae; D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase; D014805:Vitamin B 12