RESUMO
The biological methyl donor S-adenosyl-L-methionine [(S,S)-AdoMet] can spontaneously break down under physiological conditions to form the inactive diastereomer (R,S)-AdoMet, which may interfere with cell function. Although several lower organisms metabolize (R,S)-AdoMet via homocysteine methyltransferases, it is unclear how mammals deal with it. In this paper, we show that the mouse liver extracts, containing the BHMT-2 homocysteine methyltransferase candidate for a similar activity, recognizes (S,S)-AdoMet but not (R,S)-AdoMet. We find no evidence for the enzymatic breakdown of (R,S)-AdoMet in these extracts. Thus, mammals may metabolize (R,S)-AdoMet using a different strategy than other organisms.
Assuntos
Envelhecimento/metabolismo , Homocisteína S-Metiltransferase/metabolismo , Mamíferos/metabolismo , S-Adenosilmetionina/metabolismo , Animais , Betaína-Homocisteína S-Metiltransferase/metabolismo , Betaína-Homocisteína S-Metiltransferase/fisiologia , Catálise , Dípteros/genética , Dípteros/metabolismo , Helmintos/genética , Helmintos/metabolismo , Homocisteína S-Metiltransferase/fisiologia , Humanos , Fígado/enzimologia , Fígado/metabolismo , Mamíferos/genética , Camundongos , Conformação Molecular , Estresse Oxidativo , Plantas/genética , Plantas/metabolismo , S-Adenosilmetionina/química , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/fisiologia , Especificidade por Substrato , Leveduras/genética , Leveduras/metabolismoRESUMO
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.