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dc.contributor.authorBlackburn, Alison*
dc.contributor.authorBibby, Michael C.*
dc.contributor.authorLucock, M.D.*
dc.contributor.authorNicolaou, Anna*
dc.date.accessioned2009-11-10T11:42:35Z
dc.date.available2009-11-10T11:42:35Z
dc.date.issued2004
dc.identifier.citationBlackburn, A., Bibby, M.C., Lucock, M.D. and Nicolaou, A. (2004). Temporal evaluation of methionine synthase and related metabolites in the MAC15A mouse adenocarcinoma animal model. International Journal of Cancer. Vol. 112, No. 4, pp. 577-584.en
dc.identifier.urihttp://hdl.handle.net/10454/3886
dc.descriptionNoen
dc.description.abstractMethionine dependence is unique to cancer cells and defined as the inability to grow in a methionine-deprived environment even if supplemented with the metabolic precursor homocysteine. Cobalamin-dependent methionine synthase (MS) catalyses the formation of methionine and tetrahydrofolate from homocysteine and methyltetrahydrofolate, thus linking the methionine and folate pathways. The apparent altered methionine metabolism in methionine-dependent cancer cells suggests a role for MS, although results to date are conflicting. We have analysed key metabolites of the MS-associated transmethylation, transsulphuration and folate pathways of the methionine-dependent MAC15A tumour model as a function of tumour progression over a 10-day period. MS activity increased 2-fold from day I to day 10. Cysteine, homocysteine, S-adenosylmethionine and S-adenosylhomocysteine levels in tumour cytosolic fractions decreased as a function of tumour progression. Plasma cysteine levels also decreased, whilst the distribution of folates in erythrocytes was altered, with a maximum increase in methyltetrahydrofolate observed by day 5. The increasing MS activity and decreasing cysteine levels suggest an increasing methionine requirement by the tumour, whilst the induction of enzyme activity indicates that MS is not defective in the methionine-dependent MAC15A tumour. The decrease in tumour S-adenosylmethionine and S-adenosylhomocysteine levels suggests that methionine is required for some function other than cellular methylation, e.g., incorporation into protein. Overall, the results support a theory of methionine conservation in response to tumour growth, where the methionine-dependent MAC15A tumour has a higher than normal methionine requirement.en
dc.language.isoenen
dc.relation.isreferencedbyhttp://dx.doi.org/10.1002/ijc.20451en
dc.subjectMalignant tumoren
dc.subjectDigestive diseasesen
dc.subjectIntestinal diseaseen
dc.subjectColonic diseaseen
dc.subjectRodentiaen
dc.subjectMouseen
dc.subjectMetaboliteen
dc.subjectLyasesen
dc.subjectColon adenocarcinomaen
dc.subjectSulfur containing aminoaciden
dc.titleTemporal evaluation of methionine synthase and related metabolites in the MAC15A mouse adenocarcinoma animal mode.len
dc.status.refereedYesen
dc.typeArticleen
dc.type.versionNo full-text available in the repositoryen


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