Reverse methionine biosynthesis from S-adenosylmethionine in eukaryotic cells

The intracellular ratio between methionine and its activated form S-adenosy lmethionine (AdoMet) is of crucial importance for the one-carbon metabolism , AdoMet recycling into methionine was believed to be largely achieved thro ugh the methyl and the thiomethyladenosine cycles. We show here that in yea st, AdoMet recycling: actually occurs mainly through the direct AdoMet-depe ndent remethylation of homocysteine, Compelling evidences supporting this r esult were obtained owing to the identification and functional characteriza tion of two new genes, SAM4 and MHT1, that encode the yeast AdoMet-homocyst eine methyltransferase and S-methylmethionine-homocysteine methyltransferas e, respectively. Homologs of the Sam4 and Mht1 proteins exist in other euca ryotes, indicating that such enzymes would be universal and not restricted to the bacterial or fungal kingdoms. New pathways for AdoMet or S-methylmet hionine-dependent methionine synthesis are presented.