Orotic acid is a Bronsted acid and its conjugate base, the orotate anion, is able to bind to metals. Lithium orotate, for example, has been investigated for use in treating alcoholism,[4][5] and complexes of cobalt, manganese, nickel, and zinc are known.[6] The pentahydrate nickel orotate coordination complex converts into a polymeric trihydrate upon heating in water at 100 °C.[6][7][8] Crystals of the trihydrate can be obtained by hydrothermal treatment of nickel(II) acetate and orotic acid. When the reactions are run with bidentate nitrogen ligands such as 2,2'-bipyridine present, other solids can be obtained.
Inornithine transcarbamylase deficiency, an X-linked inherited and the most common urea cycle disorder, excess carbamoyl phosphate is converted into orotic acid. This leads to an increased serum ammonia level, increased serum and urinary orotic acid levels and a decreased serum blood urea nitrogen level. This also leads to an increased urinary orotic acid excretion, because the orotic acid is not being properly utilized and must be eliminated. The hyperammonemia depletes alpha-ketoglutarate leading to the inhibition of the tricarboxylic acid cycle (TCA) decreasing adenosine triphosphate (ATP) production.
Orotic aciduria is a cause of megaloblastic anaemia.
Orotic acid is a precursor to a RNA base, uracil. [10] The breast milkofsmokers has a higher concentration of orotic acid than that of a non smoking woman. It is reasoned that the smoking causes the pyrimidine biosynthesis process in the mother to be altered thus causing the orotic acid concentration to increase.[11]
A modified orotic acid (5-fluoroorotic acid) is toxic to yeast. The mutant yeasts which are resistant to 5-fluoroorotic acid require a supply of uracil.[12]
^Harvey D, Ferrier D, eds. (2008). Biochemistry(PDF) (5th ed.). Lippincott, Williams & Wilkins. p. 302.
^Bach I, Kumberger O, Schmidbaur H (1990). "Orotate complexes. Synthesis and crystal structure of lithium orotate(—I) monohydrate and magnesium bis[orotate(—I)] octahydrate". Chemische Berichte. 123 (12): 2267–2271. doi:10.1002/cber.19901231207.
^Ashihara H, Stasolla C, Loukanina N, Thorpe TA (2000). "Purine and pyrimidine metabolism in cultured white spruce (Picea glauca) cells: Metabolic fate of 14C-labeled precursors and activity of key enzymes". Physiologia Plantarum. 108: 25–33. doi:10.1034/j.1399-3054.2000.108001025.x.
^Karatas F (October 2002). "An investigation of orotic acid levels in the breastmilk of smoking and non-smoking mothers". European Journal of Clinical Nutrition. 56 (10): 958–960. doi:10.1038/sj.ejcn.1601420. PMID12373615. S2CID29181790.
Greenbaum SB (1954). "Potential Metabolic Antagonists of Orotic Acid: 6-Uracilsulfonamide and 6-Uracil Methyl Sulfone". Journal of the American Chemical Society. 76 (23): 6052–6054. doi:10.1021/ja01652a056.