Dihydroorotate dehydrogenase

DHODHdihydroorotate oxidaseDihydroorotate dehydrogenase (DHODH)dihydroorotate synthase
Dihydroorotate dehydrogenase (DHODH) is an enzyme that in humans is encoded by the DHODH gene on chromosome 16.wikipedia
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Pyrimidine metabolism

pyrimidine biosynthesisde novo'' pyrimidine synthesis pathwaypyrimidine nucleotide synthesis
The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in de novo pyrimidine biosynthesis.
Dihydroorotate dehydrogenase (DHODH) unlike CAD and UMPS is a mono-functional enzyme and is localized in the mitochondria.

Leflunomide

SU101AravaArava (drug)
The immunomodulatory drugs teriflunomide and leflunomide have been shown to inhibit DHODH.
It is a pyrimidine synthesis inhibitor that works by inhibiting dihydroorotate dehydrogenase.

Orotic acid

orotate
Class 2 DHODHs follow a stepwise mechanism, in which the breaking of the C–H bonds precedes the equilibration of iminium into orotic acid.
The compound is manufactured in the body via a mitochondrial enzyme, dihydroorotate dehydrogenase or a cytoplasmic enzyme of pyrimidine synthesis pathway.

Miller syndrome

Genée-Wiedemann syndromeGenee–WiedemannMiller
Mutations in this gene have been shown to cause Miller syndrome, also known as Genee-Wiedemann syndrome, Wildervanck-Smith syndrome or post axial acrofacial dystosis (POADS).
It is caused by a mutation in the DHODH gene.

Teriflunomide

Aubagio
The immunomodulatory drugs teriflunomide and leflunomide have been shown to inhibit DHODH.
Teriflunomide is an immunomodulatory drug inhibiting pyrimidine de novo synthesis by blocking the enzyme dihydroorotate dehydrogenase.

Enzyme

enzymologyenzymesenzymatic
Dihydroorotate dehydrogenase (DHODH) is an enzyme that in humans is encoded by the DHODH gene on chromosome 16.

Catalysis

catalyzescatalysescatalyst
The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in de novo pyrimidine biosynthesis.

Redox

oxidationoxidizedreduction
The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in de novo pyrimidine biosynthesis. In Class 1 DHODH, a basic cysteine residue catalyzes the oxidation reaction, whereas in Class 2, the serine serves this catalytic function.

4,5-Dihydroorotic acid

dihydroorotate
The protein encoded by this gene catalyzes the fourth enzymatic step, the ubiquinone-mediated oxidation of dihydroorotate to orotate, in de novo pyrimidine biosynthesis.

Inner mitochondrial membrane

mitochondrial inner membraneinner membranei'''nner '''m'''itochondrial '''m'''embrane
This protein is a mitochondrial protein located on the outer surface of the inner mitochondrial membrane (IMM).

Enzyme inhibitor

inhibitorinhibitioninhibitors
Inhibitors of this enzyme are used to treat autoimmune diseases such as rheumatoid arthritis.

Autoimmune disease

autoimmune diseasesautoimmune disorderautoimmune
Inhibitors of this enzyme are used to treat autoimmune diseases such as rheumatoid arthritis.

Rheumatoid arthritis

rheumatoidrheumatic arthritisarthritis, rheumatoid
Inhibitors of this enzyme are used to treat autoimmune diseases such as rheumatoid arthritis.

Cofactor (biochemistry)

cofactorcofactorscoenzyme
DHODH can vary in cofactor content, oligomeric state, subcellular localization, and membrane association.

Subcellular localization

localizeslocalizelocalization
DHODH can vary in cofactor content, oligomeric state, subcellular localization, and membrane association.

Membrane

membranousmembranesBiomembrane
DHODH can vary in cofactor content, oligomeric state, subcellular localization, and membrane association.

Cytosol

cytosolichyaloplasmintracellular fluid
An overall sequence alignment of these DHODH variants presents two classes of DHODHs: the cytosolic Class 1 and the membrane-bound Class 2.

Base (chemistry)

basebasicbases
In Class 1 DHODH, a basic cysteine residue catalyzes the oxidation reaction, whereas in Class 2, the serine serves this catalytic function.

Cysteine

CysL-cysteinecystein
In Class 1 DHODH, a basic cysteine residue catalyzes the oxidation reaction, whereas in Class 2, the serine serves this catalytic function.

Amino acid

amino acidsresiduesresidue
In Class 1 DHODH, a basic cysteine residue catalyzes the oxidation reaction, whereas in Class 2, the serine serves this catalytic function.

Protein dimer

heterodimerdimerhomodimer
Structurally, Class 1 DHODHs can also be divided into two subclasses, one of which forms homodimers and uses fumarate as its electron acceptor, and the other which forms heterotetramers and uses NAD+ as its electron acceptor.

Fumaric acid

fumaratefumaric acid esters(''E'')-butenedioic acid
Structurally, Class 1 DHODHs can also be divided into two subclasses, one of which forms homodimers and uses fumarate as its electron acceptor, and the other which forms heterotetramers and uses NAD+ as its electron acceptor.

Electron acceptor

acceptorterminal electron acceptoracceptors
Structurally, Class 1 DHODHs can also be divided into two subclasses, one of which forms homodimers and uses fumarate as its electron acceptor, and the other which forms heterotetramers and uses NAD+ as its electron acceptor.

Heterotetramer

heterotetramericheterotetrametric
Structurally, Class 1 DHODHs can also be divided into two subclasses, one of which forms homodimers and uses fumarate as its electron acceptor, and the other which forms heterotetramers and uses NAD+ as its electron acceptor.

Nicotinamide adenine dinucleotide

NAD + NADHNAD
Structurally, Class 1 DHODHs can also be divided into two subclasses, one of which forms homodimers and uses fumarate as its electron acceptor, and the other which forms heterotetramers and uses NAD+ as its electron acceptor.