Temporal evaluation of methionine synthase and related metabolites in the MAC15A mouse adenocarcinoma animal model

International Journal of Cancer. Journal International Du Cancer
Alison BlackburnAnna Nicolaou

Abstract

Methionine 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 1 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, whi...Continue Reading

Citations

Jul 3, 2008·Digestive Diseases and Sciences·Sakhawat H RahmanAnna Nicolaou
Apr 7, 2006·Magnetic Resonance in Medicine : Official Journal of the Society of Magnetic Resonance in Medicine·Daniel MorvanJean Claude Madelmont

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