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

Together, this pair forms a hydrophobic funnel that is suggested to serve as the insertion site for ubiquinone, in conjunction with the FMN binding cavity at the C-terminal.

DHODH depletion also resulted in increased ROS production, decreased membrane potential and cell growth retardation.

Class 2 DHODHs follow a stepwise mechanism, in which the breaking of the C–H bonds precedes the equilibration of iminium into orotic acid.

[2] Brequinar, a potent and selective inhibitor of the enzyme dihydroorotate dehydrogenase, has been shown to inhibit completely vaccinia virus in human cells.

[2][8] Its immunosuppressive effects have been attributed to the depletion of the pyrimidine supply for T cells or to more complex interferon or interleukin-mediated pathways, but nonetheless require further research.

Inhibition of DHODH activity with teriflunomide or expression with RNA interference resulted in reduced ROS generation in, and thus apoptosis of, transformed skin and prostate epithelial cells.