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An allosteric mechanism for switching between parallel tracks in mammalian sulfur metabolismстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 20 апреля 2016 г.
- Авторы: Korendyaseva T.K., Kuvatov D.N., Volkov V.A., Martinov M.V., Vitvitsky V.M., Banerjee R., Ataullakhanov F.I.
- Журнал: PLoS Computational Biology
- Том: 4
- Номер: 5
- Год издания: 2008
- Издательство: Public Library of Science
- Местоположение издательства: United States
- Первая страница: e1000076
- Аннотация: Methionine (Met) is an essential amino acid that is needed for the synthesis of S-adenosylmethionine (AdoMet), the major biological methylating agent. Methionine used for AdoMet synthesis can be replenished via remethylation of homocysteine. Alternatively, homocysteine can be converted to cysteine via the transsulfuration pathway. Aberrations in methionine metabolism are associated with a number of complex diseases, including cancer, anemia, and neurodegenerative diseases. The concentration of methionine in blood and in organs is tightly regulated. Liver plays a key role in buffering blood methionine levels, and an interesting feature of its metabolism is that parallel tracks exist for the synthesis and utilization of AdoMet. To elucidate the molecular mechanism that controls metabolic fluxes in liver methionine metabolism, we have studied the dependencies of AdoMet concentration and methionine consumption rate on methionine concentration in native murine hepatocytes at physiologically relevant concentrations (40-400 microM). We find that both [AdoMet] and methionine consumption rates do not change gradually with an increase in [Met] but rise sharply (approximately 10-fold) in the narrow Met interval from 50 to 100 microM. Analysis of our experimental data using a mathematical model reveals that the sharp increase in [AdoMet] and the methionine consumption rate observed within the trigger zone are associated with metabolic switching from methionine conservation to disposal, regulated allosterically by switching between parallel pathways. This regulatory switch is triggered by [Met] and provides a mechanism for stabilization of methionine levels in blood over wide variations in dietary methionine intake
- Добавил в систему: Атауллаханов Фазоил Иноятович