Chromatographic separation with subsequent detection of changes in conductivity as a useful tool to detect an increase in the L-dihydroorotic acid (L-DHO) content of cell lysates and serum

International Journal of Immunotherapy

Volumn 14, Issue 4, 1997, Pages 223-232

  Milbert, U ^a   Schorlemmer, H U ^a   Haun, G ^a   Zeitter, D ^a   Wunschel, M ^a   Fudali, C ^b   Ruuth, E ^a   Bartlett, R R ^c  

^a SANOFI   (France)

^b Roussel Uclaf   (France)

^c Roussel Uclaf   (France)

Author keywords

[No Author keywords available]

Indexed keywords

DIHYDROOROTIC ACID DERIVATIVE;

ANION EXCHANGE CHROMATOGRAPHY; ARTICLE; CELL LYSATE; HUMAN; HUMAN CELL; LEUKEMIA CELL LINE; SERUM;

EID: 0032454136     PISSN: 02559625     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (15)

1. Jones M.E. Pyrimidine nucleotide biosynthesis in animals: genes, enzymes, and regulation of UMP biosythesis. Ann. Rev. Biochem., 49, 253, 1980.
2. Chen J.-J., Jones M.E. The cellular location of dihydroorotate dehydrogenase: relation to de novo biosynthesis of pyn'midines. Arch. Biochem. Biophys., 176, 82, 1976.
3. Kennedy J. Distribution, subcellular location, and product inhibition of dihydroorotate oxidation in the rat. Arch. Biochem. Biophys., 157, 369, 1973.
4. Greene S., Kiyotaka W., Braatz-Trulson J., Lou L. Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide. Biochem. Pharmacol., 50, 861,1995.
5. Kuo E.A., Hambleton P.T., Kay O.P., et al. Synthesis, structure-activity relationship, and pharmacokinetic properties of dihydroorotate dehydrogenase inhibitors: 2-cyano-3-cyclopropyl-3hydroxyl-N-(3'methyl-4'(trifluoromethyl)phenyl) propenamide and related compounds. J. Med. Chem., 39, 4608, 1996.
6. Silva, H.T., Cao, W., Shorthouse, R.A.. Loftier, M., Morris R.E. In vitro and in vivo effects of leflunomide, brequinar, and cyclosporine on pyrimidine biosynthesis. Transplant. Proc., 29, 1292, 1991.
7. Williamson R.A., Yea C.M., Robson P.A., et al. Dihydroorotate dehydrogenase is a high affinity binding protein for A 771726 and mediator of a range of biological effects of the immunmodulating compound. J. Biol. Chem., 270, 22467, 1995.
8. Green S., Kiyotaka W., Braatz-Trulson J., Lou L. Inhibition of dihydroorotate dehydrogenase by the immunosuppressive agent leflunomide. Biochem. Pharmacol., 50,861,1995.
9. Zielinski T., Zeltler D., Müllner S., Bartlett R.R. Leflunomide, a reversible inhibitor of pyrimidine biosynthesis? Inflamm. Res., 44, 207, 1995.
10. Cherwinski H.M., Byare N., Ballaron S.J., Nakano G.M., Young J.M., Ranson J.T. Leflunomide interferes with pyrimidines nucleotide biosynthesis. Inflamm. Res., 44, 317, 1995
11. Brazelton T.R., Suva H., Morris R.E. Assessment of DHODH activity in whole blood: a potential pharmacodynamic assay to monitor leflunomide. J. Invest. Med., 45, 139, 1997.
12. Smith L.H., Gilmour, L. Determination of urinary carbamylaspartate and dihydro-orotate in normal subjects and in patients with hereditary orotic aciduria. J. Clin. Med., 86,1047,1975.
13. Kesner L, Aronson F.L, Silverman M., Chan P.C. Determination of orotic and dihydroorotic acids in biological fluids and tissues. Clin. Chem., 21, 353,1975.
14. Rogers L. E., Nicolaisen K. Enzymatic spectrophotometric assay for dihydroorotic acid in serum and urine. Experientia, 28, 1259, 1972.
15. DiPierro D.D., Tavazzi B., Perno C.F., et al. An ion-pairing high-performance liquid Chromatographie method for the direct simultaneous determination of nucleotides, deoxynucleotides, nicotinic coenzymes, oxypurines, nucleosides, and bases in perchloric acid cell extracts. Analyt. Biochem., 231,407, 1995.