Disease relevance of L-Dihydroorotic acid

• Interconversion of carbamayl-L-aspartate and L-dihydroorotate by dihydroorotase from mouse Ehrlich ascites carcinoma [1].
• Escherichia coli dihydroorotase has been crystallized in the presence of the product, L-dihydroorotate (L-DHO), and the structure refined at 1.9A resolution [2].
• Dihydroorotase +4,5-L-dihydro-orotate amidohydrolase [EC 3.5.2.3]), which catalyzes the reversible cyclization of N-carbamyl-L-aspartate to L-dihydroorotate, has been purified from orotate-grown Clostridium oroticum [3].

High impact information on L-Dihydroorotic acid

• This in vitro binding does not require dihydroorotic acid, the physiological inducer of URA3 [4].
• In addition, we showed that UASURA contains a constitutive activating element which can stimulate transcription from a heterologous promoter independently of dihydroorotic acid and PPR1 [4].
• Leflunomide (25 and 50 microM), like Brequinar (0.5 and 1 microM), a demonstrated dihydroorotic-acid dehydrogenase inhibitor, was cytostatic, not cytotoxic, with proliferation being halted in the G1 phase [5].
• Superoxide production and electron transport in mitochondrial oxidation of dihydroorotic acid [6].
• Dihydroorotase (DHOase, EC 3.5.2.3) is a zinc enzyme that catalyzes the reversible cyclization of N-carbamyl-L-aspartate to L-dihydroorotate in the third reaction of the de novo pathway for biosynthesis of pyrimidine nucleotides [7].

Biological context of L-Dihydroorotic acid

• The inhibition exhibited mixed-type kinetics towards both substrates, dihydroorotic acid and coenzyme Q [8].
• The complete nucleotide sequence of the URA1 gene encoding dihydroorotic acid dehydrogenase (DHOdehase) is presented [9].
• The Vmax is increased for both the synthesis and hydrolysis of L-dihydroorotate [10].
• The different effects of substrate and L-dihydroorotic acid on the pK suggest that the binding modes of these two ligands may be different and suggest a structural basis for the mutally exclusive substrate specificities of dihydropyrimidine amidohydrolase and dihydroorotase [11].
• The data in vitro are supported by studies on the nutritional requirements of the respiration-deficient cells and by the incorporation in vivo of labelled dihydroorotic acid into the acid-insoluble fraction of the cells [12].

Anatomical context of L-Dihydroorotic acid

• Synthesis and central nervous system actions of thyrotropin-releasing hormone analogues containing a dihydroorotic acid moiety [13].

Associations of L-Dihydroorotic acid with other chemical compounds

• A series of thyrotropin-releasing hormone (TRH) analogues in which the pyroglutamic acid residue was replaced by (S)-4,5-dihydroorotic acid (Dio-OH) and the related derivatives were prepared [13].
• Dihydroorotate dehydrogenase (DHODH) is a flavoprotein that catalyses the oxidation of L-dihydroorotate to orotate, the fourth sequential step in the de novo pyrimidine nucleotide synthesis pathway [14].
• Thus, the flavin enzyme, dihydroorotic acid dehydrogenase, but not glutathione reductase, appears to be a target of this riboflavin antagonist [15].
• These observations suggest an interference by actinomycin D in the biogenesis of the enzyme dihydroorotic acid dehydrogenase [16].
• In the case of plant DHO-DH the dehydrogenation of analogues was as follows: Dihydroorotic acid (DHO) (control, 100%), DHO-hydrazide (40%), azaDHO (13%), azaDHO-ethyl ester (23%), azaDHO-hydrazide (11%), dihydrouracil (0%), dihydrothymine (0%) [17].

Analytical, diagnostic and therapeutic context of L-Dihydroorotic acid

• A sensitive, nonradiometric assay for dihydroorotic acid dehydrogenase using anion-exchange high-performance liquid chromatography [18].

References