Modulation of methylenetetrahydrofolate reductase activity by S-adenosylmethionine and by dihydrofolate and its polyglutamate analogues
dc.contributor.author | Matthews, Rowena Green | en_US |
dc.contributor.author | Daubner, S. Colette | en_US |
dc.date.accessioned | 2006-04-07T17:56:18Z | |
dc.date.available | 2006-04-07T17:56:18Z | |
dc.date.issued | 1982 | en_US |
dc.identifier.citation | Matthews, Rowena G., Daubner, S. Colette (1982)."Modulation of methylenetetrahydrofolate reductase activity by S-adenosylmethionine and by dihydrofolate and its polyglutamate analogues." Advances in Enzyme Regulation 20(): 123-131. <http://hdl.handle.net/2027.42/24098> | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/B6T3T-47DKT3V-D/2/9e1d1bddda51b6a1cdfb93447b43c33b | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/24098 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=7051769&dopt=citation | en_US |
dc.description.abstract | Methylenetetrahydrofolate reductase catalyzes the reduction of methylenetetrahydrofolate ot methyltetrahydrofolate. This reaction commits one carbon units to the pathways of adenosylmethionine-dependent methylation in mammalian cells. We have purified the pig liver enzyme to homogeneity and shown that it contains FAD as a non-covalently bound prosthetic group. Methylenetetrahydrofolate is not only a substrate for the reductase, but also for thymidylate synthase and for methylenetetrahydrofolate dehydrogenase. The latter reaction leads to utilization of one carbon units in de novo purine biosynthesis. A prior, one might expect that methylenetetrahydrofolate reductase activity would be modulated by cellular requirements for de novo biosynthesis of purines and pyrimidines, as well as by cellular levels of adenosylmethionine. Methylenetetrahydrofolate reductase is inhibited by dihydrofolate and its polyglutamate analogues. The Kl is 6.5 [mu] for dihydrofolate and decreases with each additional glutamyl residue to a minimum value of 0.013 [mu] for dihydropteroylhexaglutamate. The I50 for dihydropteroylhexaglutamate inhibition of reductase activity in the presence of 0.5 [mu] methylenetetrahydropteroylhexaglutamate is 0.07 [mu]. We proposed that stimulation of thymidylate synthease activity (as in the replicating cell) may lead to elevations in the steady state levels of cellular dihydrofolate derivatives and to resultant inhibition of methylenetetrahydrofolate reductase activity. Thus methylenetetrahydrofolate derivatives would be spared for purine and pyrimidine biosynthesis.We have also examined the inhibition of methylenetetrahydrofolate reductase by adenosylmethionine, which serves as an allosteric effector of the enzymatic activity. Adenosylmethionine induces a slow transition in the enzyme, and leads to the inhibition of NADPH-menadione. NADPH-methylenetetrahydrofolate and methyltetrahydrofolate-menadione oxido-reductase activities. | en_US |
dc.format.extent | 421104 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.title | Modulation of methylenetetrahydrofolate reductase activity by S-adenosylmethionine and by dihydrofolate and its polyglutamate analogues | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Public Health | en_US |
dc.subject.hlbsecondlevel | Internal Medicine and Specialties | en_US |
dc.subject.hlbsecondlevel | Chemistry | en_US |
dc.subject.hlbsecondlevel | Chemical Engineering | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbtoplevel | Engineering | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | The University of Michigan, Ann Arbor, Michigan 48109, USA | en_US |
dc.contributor.affiliationother | The Department of Biological Chemistry and The Biophysics Research Division, | en_US |
dc.identifier.pmid | 7051769 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/24098/1/0000355.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/0065-2571(82)90012-7 | en_US |
dc.identifier.source | Advances in Enzyme Regulation | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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