ExplorEnz: EC 1.3.1.14

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1.3.1.14

Accepted name:

dihydroorotate dehydrogenase (NAD⁺)

Reaction:

(S)-dihydroorotate + NAD⁺ = orotate + NADH + H⁺

Other name(s):

orotate reductase (NADH); orotate reductase (NADH₂); DHOdehase (ambiguous); DHOD (ambiguous); DHODase (ambiguous); dihydroorotate oxidase, pyrD (gene name)

Systematic name:

(S)-dihydroorotate:NAD⁺ oxidoreductase

Comments:

Binds FMN, FAD and a [2Fe-2S] cluster. The enzyme consists of two subunits, an FMN binding catalytic subunit and a FAD and iron-sulfur binding electron transfer subunit [4]. The reaction, which takes place in the cytosol, is the only redox reaction in the de-novo biosynthesis of pyrimidine nucleotides. Other class 1 dihydroorotate dehydrogenases use either fumarate (EC 1.3.98.1) or NADP⁺ (EC 1.3.1.15) as electron acceptor. The membrane bound class 2 dihydroorotate dehydrogenase (EC 1.3.5.2) uses quinone as electron acceptor.

Links to other databases:

BRENDA, EXPASY, Gene, KEGG, MetaCyc, PDB, CAS registry number: 37255-26-8

References:

1.	Friedmann, H.C. and Vennesland, B. Purification and properties of dihydroorotic acid dehydrogenase. J. Biol. Chem. 233 (1958) 1398–1406. [PMID: 13610849]
2.	Friedmann, H.C. and Vennesland, B. Crystalline dihydroorotic dehydrogenase. J. Biol. Chem. 235 (1960) 1526–1532. [PMID: 13825167]
3.	Lieberman, I. and Kornberg, A. Enzymic synthesis and breakdown of a pyrimidine, orotic acid. I. Dihydro-orotic dehydrogenase. Biochim. Biophys. Acta 12 (1953) 223–234. [DOI] [PMID: 13115431]
4.	Nielsen, F.S., Andersen, P.S. and Jensen, K.F. The B form of dihydroorotate dehydrogenase from Lactococcus lactis consists of two different subunits, encoded by the pyrDb and pyrK genes, and contains FMN, FAD, and [FeS] redox centers. J. Biol. Chem. 271 (1996) 29359–29365. [DOI] [PMID: 8910599]
5.	Rowland, P., Nørager, S., Jensen, K.F. and Larsen, S. Structure of dihydroorotate dehydrogenase B: electron transfer between two flavin groups bridged by an iron-sulphur cluster. Structure 8 (2000) 1227–1238. [DOI] [PMID: 11188687]
6.	Kahler, A.E., Nielsen, F.S. and Switzer, R.L. Biochemical characterization of the heteromeric Bacillus subtilis dihydroorotate dehydrogenase and its isolated subunits. Arch. Biochem. Biophys. 371 (1999) 191–201. [DOI] [PMID: 10545205]
7.	Marcinkeviciene, J., Tinney, L.M., Wang, K.H., Rogers, M.J. and Copeland, R.A. Dihydroorotate dehydrogenase B of Enterococcus faecalis. Characterization and insights into chemical mechanism. Biochemistry 38 (1999) 13129–13137. [DOI] [PMID: 10529184]

[EC 1.3.1.14 created 1972, modified 2011]