Gene Targets > dihydroorotase activity
Page last updated: 2024-10-24

dihydroorotase activity

Definition

Target type: molecularfunction

Catalysis of the reaction: (S)-dihydroorotate + H2O = N-carbamoyl-L-aspartate + H+. [EC:3.5.2.3, RHEA:24296]

Dihydroorotase activity is a crucial enzymatic function involved in the de novo biosynthesis of pyrimidine nucleotides, a fundamental process for DNA and RNA synthesis. This enzyme catalyzes the reversible conversion of carbamoyl aspartate to dihydroorotate. This reaction involves a two-step mechanism: first, carbamoyl aspartate undergoes a ring closure to form a cyclic intermediate, followed by a tautomerization to yield dihydroorotate. Dihydroorotase exhibits a high degree of specificity for its substrates, and its activity is essential for maintaining adequate pyrimidine nucleotide pools within the cell. Deficiencies in dihydroorotase activity can lead to severe metabolic disorders, such as orotic aciduria, characterized by the accumulation of orotic acid in body fluids. This enzyme's activity is tightly regulated by various factors, including substrate availability, cofactor levels, and cellular metabolic status, ensuring proper pyrimidine nucleotide homeostasis.'
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Proteins (2)

ProteinDefinitionTaxonomy
Dihydroorotate dehydrogenase (quinone), mitochondrialA dihydroorotate dehydrogenase (quinone), mitochondrial that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q02127]Homo sapiens (human)
CAD proteinA multifunctional protein CAD that is encoded in the genome of human. [PRO:DNx, UniProtKB:P27708]Homo sapiens (human)

Compounds (31)

CompoundDefinitionClassesRoles
ureidosuccinic acidN-carbamoylaspartic acid : An N-carbamoylamino acid that is aspartic acid with one of its amino hydrogens replaced by a carbamoyl group.

ureidosuccinic acid: RN given refers to (DL)-isomer		aspartic acid derivative;
C4-dicarboxylic acid;
N-carbamoyl-amino acid		Escherichia coli metabolite;
human metabolite;
Saccharomyces cerevisiae metabolite
2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone2,3-dimethoxy-5-methyl-6-decyl-1,4-benzoquinone: ubiquinol analog

6-decylubiquinone : A member of the class of 1,4-benzoquinones that is 2,3-dimethoxybenzoquinone which has been substituted at positions 5 and 6 by decyl and methyl groups.		1,4-benzoquinonescofactor
lapachollapachol : A hydroxy-1,4-naphthoquinone that is 1,4-naphthoquinone substituted by hydroxy and 3-methylbut-2-en-1-yl groups at positions 2 and 3, respectively. It is a natural compound that exhibits antibacterial and anticancer properties, first isolated in 1882 from the bark of Tabebuia avellanedae.
leflunomideleflunomide : A monocarboxylic acid amide obtained by formal condensation of the carboxy group of 5-methyl-1,2-oxazole-4-carboxylic acid with the anilino group of 4-(trifluoromethyl)aniline. The prodrug of teriflunomide.

Leflunomide: An isoxazole derivative that inhibits dihydroorotate dehydrogenase, the fourth enzyme in the pyrimidine biosynthetic pathway. It is used an immunosuppressive agent in the treatment of RHEUMATOID ARTHRITIS and PSORIATIC ARTHRITIS.		(trifluoromethyl)benzenes;
isoxazoles;
monocarboxylic acid amide		antineoplastic agent;
antiparasitic agent;
EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitor;
EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor;
hepatotoxic agent;
immunosuppressive agent;
non-steroidal anti-inflammatory drug;
prodrug;
pyrimidine synthesis inhibitor;
tyrosine kinase inhibitor
niflumic acidNiflumic Acid: An analgesic and anti-inflammatory agent used in the treatment of rheumatoid arthritis.aromatic carboxylic acid;
pyridines
quinone1,4-benzoquinone : The simplest member of the class of 1,4-benzoquinones, obtained by the formal oxidation of hydroquinone to the corresponding diketone. It is a metabolite of benzene.

benzoquinone : The simplest members of the class of benzoquinones, consisting of cyclohexadiene which is substituted by two oxo groups.

quinone : Compounds having a fully conjugated cyclic dione structure, such as that of benzoquinones, derived from aromatic compounds by conversion of an even number of -CH= groups into -C(=O)- groups with any necessary rearrangement of double bonds (polycyclic and heterocyclic analogues are included).		1,4-benzoquinonescofactor;
human xenobiotic metabolite;
mouse metabolite
cinchophencinchophen: was heading 1963-94; ACIPHENOCHINOLIUM was see CHINOPHEN 1978-94; use QUINOLINES to search CINCHOPHEN 1966-94quinolines
oxycinchophenquinolines
clonixinclonixin : A pyridinemonocarboxylic acid that is nicotinic acid substituted at position 2 by a (2-methyl-3-chlorophenyl)amino group. Used (as its lysine salt) for treatment of renal colic, muscular pain and moderately severe migraine attacks.

Clonixin: Anti-inflammatory analgesic.		aminopyridine;
organochlorine compound;
pyridinemonocarboxylic acid		antipyretic;
EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor;
lipoxygenase inhibitor;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug;
platelet aggregation inhibitor;
vasodilator agent
flunixinflunixin : A pyridinemonocarboxylic acid that is nicotinic acid substituted at position 2 by a 2-methyl-3-(trifluoromethyl)phenylamino group. A relatively potent non-narcotic, nonsteroidal analgesic with anti-inflammatory, anti-endotoxic and anti-pyretic properties; used in veterinary medicine (usually as the meglumine salt) for treatment of horses, cattle and pigs.aminopyridine;
organofluorine compound;
pyridinemonocarboxylic acid		antipyretic;
EC 1.14.99.1 (prostaglandin-endoperoxide synthase) inhibitor;
non-narcotic analgesic;
non-steroidal anti-inflammatory drug
brequinarbrequinar : A quinolinemonocarboxylic acid that is quinoline substituted by 2'-fluoro[1,1'-biphenyl]-4-yl, methyl, carboxy and fluoro groups at positions 2, 3, 4, and 6, respectively. It is an inhibitor of dihydroorotate dehydrogenase, an enzyme that is required for de novo pyrimidine biosynthesis. The compound exhibits antineoplastic and antiviral properties.biphenyls;
monocarboxylic acid;
monofluorobenzenes;
quinolinemonocarboxylic acid		anticoronaviral agent;
antimetabolite;
antineoplastic agent;
antiviral agent;
EC 1.3.5.2 [dihydroorotate dehydrogenase (quinone)] inhibitor;
immunosuppressive agent;
pyrimidine synthesis inhibitor
atovaquoneatovaquone : A naphthoquinone compound having a 4-(4-chlorophenyl)cyclohexyl group at the 2-position and a hydroxy substituent at the 3-position.

Atovaquone: A hydroxynaphthoquinone that has antimicrobial activity and is being used in antimalarial protocols.		hydroxy-1,2-naphthoquinone
hydrolapacholhydrolapachol: inhibits mitochondrial respiratory chain
3',4'-dihydroxyflavone3',4'-dihydroxyflavone: inhibitors of arachidonic acid peroxidation
nsc-126771dichloroallyl lawsone: structure
cyclo(l-phe-l-pro)organic molecular entitymetabolite
piperinepiperine : A N-acylpiperidine that is piperidine substituted by a (1E,3E)-1-(1,3-benzodioxol-5-yl)-5-oxopenta-1,3-dien-5-yl group at the nitrogen atom. It is an alkaloid isolated from the plant Piper nigrum.benzodioxoles;
N-acylpiperidine;
piperidine alkaloid;
tertiary carboxamide		food component;
human blood serum metabolite;
NF-kappaB inhibitor;
plant metabolite
2-phenylamino-4-methyl-5-acetylthiazole2-phenylamino-4-methyl-5-acetylthiazole: structure in first source
pd 156252
n-(3,5-dichlorophenyl)-2-methyl-3-nitrobenzamideN-(3,5-dichlorophenyl)-2-methyl-3-nitrobenzamide: inhibits dihydroorotate dehydrogenase from P. falciparum; structure in first source
isobavachalconeisobavachalcone : A member of the class of chalcones that is trans-chalcone substituted by hydroxy groups at positions 4, 2' and 4' and a prenyl group at position 3'.

isobavachalcone: RN given for (E)-isomer; structure in first source		chalcones;
polyphenol		antibacterial agent;
metabolite;
platelet aggregation inhibitor
cyclosporineramihyphin A: one of the metabolites produced by Fusarium sp. S-435; RN given refers to cpd with unknown MFhomodetic cyclic peptideanti-asthmatic drug;
anticoronaviral agent;
antifungal agent;
antirheumatic drug;
carcinogenic agent;
dermatologic drug;
EC 3.1.3.16 (phosphoprotein phosphatase) inhibitor;
geroprotector;
immunosuppressive agent;
metabolite
ascofuranoneascofuranone : A dihydroxybenzaldehyde that is 2,4-dihydroxybenzaldehyde which is substituted by a (2E,6E)-7-[(2S)-5,5-dimethyl-4-oxotetrahydrofuran-2-yl]-3-methylocta-2,6-dien-1-yl group at position 3, chlorine at position 5, and a methyl group at position 6. A meroterpenoid produced by the soil fungus, Acremonium sclerotigenum. It is a promising drug candidate against the tropical disease, African trypanosomiasis.

ascofuranone: structure		dihydroxybenzaldehyde;
meroterpenoid;
monochlorobenzenes;
olefinic compound;
resorcinols;
sesquiterpenoid;
tetrahydrofuranone		angiogenesis inhibitor;
antilipemic drug;
antineoplastic agent;
antiprotozoal drug;
fungal metabolite
cyclo(prolyl-valyl)piperazinonemetabolite
cyclo(leucyl-prolyl)cyclo(L-Leu-L-Pro) : A homodetic cyclic peptide composed from leucyl and prolyl residues.

cyclo(leucyl-prolyl): structure in first source		dipeptide;
homodetic cyclic peptide;
pyrrolopyrazine		bacterial metabolite;
marine metabolite
vidofludimusvidofludimus: a dihydroorotate dehydrogenase inhibitor; structure in first source
ascochlorinascochlorin : A dihydroxybenzaldehyde that is 2,4-dihydroxybenzaldehyde which is substituted by a (1E,3E)-3-methyl-1-[(1R,2R,6R)-1,2,6-trimethyl-3-oxocyclohexyl]penta-1,3-dien-5-yl group at position 3, chlorine at position 5, and a methyl group at position 6. A meroterpenoid produced by several fungi including Ascochyta viciae . It exhibits anticancer, antifungal and antiprotozoal activities.

ascochlorin: structure in first source		cyclohexanones;
dihydroxybenzaldehyde;
meroterpenoid;
monochlorobenzenes;
olefinic compound;
resorcinols;
sesquiterpenoid		angiogenesis inhibitor;
antifungal agent;
antineoplastic agent;
antiprotozoal drug;
fungal metabolite
brequinar sodiumbrequinar sodium : An organic sodium salt of brequinar.organic sodium saltanticoronaviral agent;
antimetabolite;
antineoplastic agent;
antiviral agent;
EC 1.3.5.2 [dihydroorotate dehydrogenase (quinone)] inhibitor;
immunosuppressive agent;
pyrimidine synthesis inhibitor
dsm 74
teriflunomide(trifluoromethyl)benzenes;
aromatic amide;
enamide;
enol;
nitrile;
secondary carboxamide		drug metabolite;
EC 1.3.98.1 [dihydroorotate oxidase (fumarate)] inhibitor;
hepatotoxic agent;
non-steroidal anti-inflammatory drug;
tyrosine kinase inhibitor
2-ethylphenyl 4-(3-ethylureido)benzenesulfonate2-ethylphenyl 4-(3-ethylureido)benzenesulfonate: has antineoplastic activity; structure in first source
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