Show simple item record

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.
dc.identifier.urihttp://hdl.handle.net/10454/3886
dc.descriptionNo
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.
dc.language.isoen
dc.subjectMalignant tumor
dc.subjectDigestive diseases
dc.subjectIntestinal disease
dc.subjectColonic disease
dc.subjectRodentia
dc.subjectMouse
dc.subjectMetabolite
dc.subjectLyases
dc.subjectColon adenocarcinoma
dc.subjectSulfur containing aminoacid
dc.titleTemporal evaluation of methionine synthase and related metabolites in the MAC15A mouse adenocarcinoma animal mode.l
dc.status.refereedYes
dc.typeArticle
dc.type.versionNo full-text in the repository
dc.identifier.doihttps://doi.org/10.1002/ijc.20451
dc.openaccess.statusclosedAccess


This item appears in the following Collection(s)

Show simple item record