Mammalian mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase derived from a trifunctional methylenetetrahydrofolate dehydrogenase-cyclohydrolase-synthetase.
We have isolated the cDNA and the gene encoding the murine cytoplasmic methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase (DCS). Comparison of these sequences with the 3'-untranslated region of the mitochondrial NAD(+)-dependent methylenetetrahydrofolate dehydrogenase-cyclohydrolase (mt-DC) revealed areas of significant homology. Both exon and intron sequences of the synthetase domain of DCS are homologous to sequences in the untranslated region of mt-DC. A similar comparison between the mt-DC and the DCS sequences of humans as well as Drosophila supports the conclusion that in higher eukaryotes the bifunctional mt-DC replaced a trifunctional precursor through inactivation of the synthetase domain. The mt-DC should be considered in models of one-carbon folate fluxes in mammals.
Patel
Harshila
H
Department of Biochemistry, McGill University, 3655 Promenade Sir William Osler, Montréal, QC, Canada H3G 1Y6.
Christensen
Karen E
KE
Mejia
Narciso
N
MacKenzie
Robert E
RE
D020413:3' Untranslated Regions; D000619:Aminohydrolases / Q000737:chemistry* / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D018076:DNA, Complementary; D005091:Exons; D005492:Folic Acid / Q000378:metabolism; D005574:Formate-Tetrahydrofolate Ligase / Q000235:genetics*; D007438:Introns; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP) / Q000737:chemistry* / Q000235:genetics*; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry* / Q000235:genetics*; D017434:Protein Structure, Tertiary; D012689:Sequence Homology, Nucleic Acid
D020413:3' Untranslated Regions; D018076:DNA, Complementary; D009097:Multienzyme Complexes; C055342:methylene tetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase; C021836:formyl-methenyl-methylenetetrahydrofolate synthetase; D005492:Folic Acid; D008754:Methylenetetrahydrofolate Dehydrogenase (NADP); D000619:Aminohydrolases; D005574:Formate-Tetrahydrofolate Ligase