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Methionine synthase supports tumour tetrahydrofolate pools.

ABSTRACT: Mammalian cells require activated folates to generate nucleotides for growth and division. The most abundant circulating folate species is 5-methyl tetrahydrofolate (5-methyl-THF), which is used to synthesize methionine from homocysteine via the cobalamin-dependent enzyme methionine synthase (MTR). Cobalamin deficiency traps folates as 5-methyl-THF. Here, we show using isotope tracing that MTR is only a minor source of methionine in cell culture, tissues or xenografted tumours. Instead, MTR is required for cells to avoid folate trapping and assimilate 5-methyl-THF into other folate species. Under conditions of physiological extracellular folates, genetic MTR knockout in tumour cells leads to folate trapping, purine synthesis stalling, nucleotide depletion and impaired growth in cell culture and as xenografts. These defects are rescued by free folate but not one-carbon unit supplementation. Thus, MTR plays a crucial role in liberating THF for use in one-carbon metabolism.

SUBMITTER: Ghergurovich JM

PROVIDER: S-EPMC9284419 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Human methionine synthase reductase is a molecular chaperone for human methionine synthase.

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2012-06-11 | GSE32972 | GEO

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2012-06-11 | GSE32971 | GEO

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Gene expression comparison of L. reuteri ATCC PTA 6475 and tetrahydrofolate synthase 1 mutant

Project description:Gene expression comparison of L. reuteri ATCC PTA 6475 and tetrahydrofolate synthase 1 in MRS medium in anaerobic conditions at 37C. Includes 3 biological replicates and dye-swaps, with one additional replicate for ATCC PTA 6475 versus tetrahydrofolate synthase 1 mutant. Reference time point is L. reuteri ATCC PTA 6475.

2012-06-10 | E-GEOD-32971 | biostudies-arrayexpress

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