Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1976 Jul 1;157(1):105–109. doi: 10.1042/bj1570105

The role of tetrahydrofolate dehydrogenase in the hepatic supply of tetrahydrobiopterin in rats.

K J Stone
PMCID: PMC1163821  PMID: 962851

Abstract

The reduction of 7,8-dihydrobiopterin to 5,6,7,8-tetrahydrobiopterin by rat liver tetrahydrofolate dehydrogenase (5,6,7,8-tetrahydrofolate-NADP+ oxidoreductase, EC 1.5.1.3) is competitively inhibited by trimethoprim lactate (apparent Ki 0.285 muM). An apparent Michaelis constant of 43 muM for dihydrobiopterin was obtained, which is 430 times higher than the reported Km for dihydrofolate with this enzyme. The reduction of dihydrobiopterin is thus more susceptible to inhibition by trimethoprim lactate than is the reduction of dihydrofolate. However, intraperitoneal administration of trimethoprim had no significant effect on the hepatic supply of tetrahydrobiopterin in rats.

Full text

PDF
107

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Burchall J. J., Hitchings G. H. Inhibitor binding analysis of dihydrofolate reductases from various species. Mol Pharmacol. 1965 Sep;1(2):126–136. [PubMed] [Google Scholar]
  2. Danks D. M., Cotton R. G., Schlesinger P. Letter: Tetrahydrobiopterin treatment of variant form of phenylketonuria. Lancet. 1975 Nov 22;2(7943):1043–1043. doi: 10.1016/s0140-6736(75)90335-9. [DOI] [PubMed] [Google Scholar]
  3. England J. M., Coles M. Effect of co-trimoxazole on phenylalanine metabolism in man. Lancet. 1972 Dec 23;2(7791):1341–1343. doi: 10.1016/s0140-6736(72)92780-8. [DOI] [PubMed] [Google Scholar]
  4. GOODFRIEND T. L., KAUFMAN S. Phenylalanine metabolism and folic acid antagonists. J Clin Invest. 1961 Sep;40:1743–1750. doi: 10.1172/JCI104397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hillcoat B. L., Nixon P. F., Blakley R. L. Effect of substrate decomposition on the spectrophotometric assay of dihydrofolate reductase. Anal Biochem. 1967 Nov;21(2):178–189. doi: 10.1016/0003-2697(67)90179-0. [DOI] [PubMed] [Google Scholar]
  6. Jarabak J., Bachur N. R. A soluble dihydrofolate reductase from human placenta: purification and properties. Arch Biochem Biophys. 1971 Feb;142(2):417–425. doi: 10.1016/0003-9861(71)90505-4. [DOI] [PubMed] [Google Scholar]
  7. KAUFMAN S. STUDIES ON THE STRUCTURE OF THE PRIMARY OXIDATION PRODUCT FORMED FROM TETRAHYDROPTERIDINES DURING PHENYLALAMINE HYDROXYLATION. J Biol Chem. 1964 Jan;239:332–338. [PubMed] [Google Scholar]
  8. Kettler R., Bartholini G., Pletscher A. In vivo enhancement of tyrosine hydroxylation in rat striatum by tetrahydrobiopterin. Nature. 1974 May 31;249(456):476–478. doi: 10.1038/249476a0. [DOI] [PubMed] [Google Scholar]
  9. LEVITT M., SPECTOR S., SJOERDSMA A., UDENFRIEND S. ELUCIDATION OF THE RATE-LIMITING STEP IN NOREPINEPHRINE BIOSYNTHESIS IN THE PERFUSED GUINEA-PIG HEART. J Pharmacol Exp Ther. 1965 Apr;148:1–8. [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. Musacchio J. M., D'Angelo G. L., McQueen C. A. Dihydropteridine reductase: implication on the regulation of catecholamine biosynthesis. Proc Natl Acad Sci U S A. 1971 Sep;68(9):2087–2091. doi: 10.1073/pnas.68.9.2087. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. NAGATSU T., LEVITT M., UDENFRIEND S. TYROSINE HYDROXYLASE. THE INITIAL STEP IN NOREPINEPHRINE BIOSYNTHESIS. J Biol Chem. 1964 Sep;239:2910–2917. [PubMed] [Google Scholar]
  13. Sharpstone P. The renal handling of trimethoprim and sulphamethoxazole in man. Postgrad Med J. 1969 Nov;45(Suppl):38–42. [PubMed] [Google Scholar]
  14. Stone K. J., Townsley B. H. The effect of L-ascorbate on catecholamine biosynthesis. Biochem J. 1973 Mar;131(3):611–613. doi: 10.1042/bj1310611. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES