title: Methenyltetrahydrofolate synthetase is a high-affinity catecholamine-binding protein.
abstract: Recombinant mouse 5,10-methenyltetrahydrofolate synthetase (MTHFS) was expressed in Escherichia coli and shown to co-purify with a chromophore that had a lambda(max) at 320nm. The chromophore remained bound to MTHFS during extensive dialysis, but dissociated from MTHFS when its substrate, 5-formyltetrahydrofolate, was bound. The chromophore was identified as an oxidized catecholamine by mass spectrometry and absorption spectroscopy. Purified recombinant mouse MTHFS and rabbit liver MTHFS proteins were shown to bind oxidized N-acetyldopamine (NADA) tightly. The addition of NADA to cell culture medium accelerated markedly folate turnover and decreased both folate accumulation and total cellular folate concentrations in MCF-7 cells. Expression of the MTHFS cDNA in MCF-7 cells increased the concentration of NADA required to deplete cellular folate. The results of this study are the first to identify a link between catecholamines and one-carbon metabolism and demonstrate that NADA accelerates folate turnover and impairs cellular folate accumulation in MCF-7 cells.
authors.affiliation: Cornell University, Division of Nutritional Sciences, Ithaca, NY 14853, USA.
authors.forename: Montserrat C
authors.initials: MC
authors.lastname: Anguera
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Stover
mesh_terms: D000818:Animals; D001665:Binding Sites; D001943:Breast Neoplasms / Q000737:chemistry* / Q000378:metabolism*; D019731:Carbon-Nitrogen Ligases / Q000737:chemistry* / Q000378:metabolism*; D002395:Catecholamines / Q000737:chemistry* / Q000378:metabolism*; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D051379:Mice; D011485:Protein Binding; D011817:Rabbits; D013379:Substrate Specificity
chemical_list: D002395:Catecholamines; D005492:Folic Acid; D019731:Carbon-Nitrogen Ligases; C021557:5,10-methenyltetrahydrofolate synthetase