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Chemical Compound Review

leucovorin     2-[[4-[(2-amino-5-methanoyl- 4-oxo-1,6,7,8...

Synonyms: folinate, Leucal, Welcovorin, Levoleucovorin, n5-formyl-thf, ...
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Disease relevance of folinic acid


High impact information on folinic acid


Biological context of folinic acid

  • The functional expression of the mutated RFC1 reduced the growth requirement for 5-CHO-THF by a factor of 30, compared with only a 3-fold decrease in the MTX IC50 [4].
  • The ability of formyl-H4F to enhance the binding of QscR to a specific region upstream of one of the serine cycle operons was demonstrated in gel retardation experiments [5].
  • The VPA plasma kinetics were not changed by any of the application regimens of 5-CHO-THF [6].
  • Oral dose proportionality and pharmacokinetics of leucovorin [(d,l)-5-formyltetrahydrofolate (5-formyl-THF)] were studied in 30 healthy male subjects [7].

Anatomical context of folinic acid


Associations of folinic acid with other chemical compounds


Gene context of folinic acid

  • A variant line (CEM-7A) "overproducing" the reduced folate/MTX carrier system was isolated from human CCRF-CEM leukemia cells grown under selective conditions in medium containing 0.25 nM 5-formyl-THF as the sole folate source [12].
  • 5-CHO-THF supplementation cut the exencephaly rates into half even at high maternal plasma levels of VPA (p less than 0.005, chi 2-test); resorption rates were not affected [6].

Analytical, diagnostic and therapeutic context of folinic acid

  • The investigation of the folate metabolite pattern (determined by HPLC) showed that 5-CHO-THF and 5-methyl-tetrahydrofolic acid (5-CH3-THF) were the main metabolites in untreated mice [6].
  • In a randomized cross-over design, 24 fasted subjects were given 4 of a series of 5 single test doses between 20 and 100 mg, at 1-week intervals, of 5-formyl-THF as an oral solution of leucovorin calcium [7].


  1. Non-ketotic hyperglycinaemia due to a deficiency of T-protein in the glycine cleavage system in liver and brain. Schutgens, R.B., Ket, J.L., Hayasaka, K., Tada, K. J. Inherit. Metab. Dis. (1986) [Pubmed]
  2. Methotrexate rescue by 5-methyltetrahydrofolate or 5-formyltetrahydrofolate in lymphoblast cell lines. Dudman, N.P., Slowiaczek, P., Tattersall, M.H. Cancer Res. (1982) [Pubmed]
  3. Cloning and characterization of methenyltetrahydrofolate synthetase from Saccharomyces cerevisiae. Holmes, W.B., Appling, D.R. J. Biol. Chem. (2002) [Pubmed]
  4. A reduced folate carrier mutation produces substrate-dependent alterations in carrier mobility in murine leukemia cells and methotrexate resistance with conservation of growth in 5-formyltetrahydrofolate. Zhao, R., Assaraf, Y.G., Goldman, I.D. J. Biol. Chem. (1998) [Pubmed]
  5. QscR-mediated transcriptional activation of serine cycle genes in Methylobacterium extorquens AM1. Kalyuzhnaya, M.G., Lidstrom, M.E. J. Bacteriol. (2005) [Pubmed]
  6. Valproic acid-induced neural tube defects: reduction by folinic acid in the mouse. Trotz, M., Wegner, C., Nau, H. Life Sci. (1987) [Pubmed]
  7. Absorption kinetics of orally administered leucovorin calcium. McGuire, B.W., Sia, L.L., Haynes, J.D., Kisicki, J.C., Gutierrez, M.L., Stokstad, E.L. NCI monographs : a publication of the National Cancer Institute. (1987) [Pubmed]
  8. Initiation of protein synthesis in isolated mitochondria and chloroplasts. Lucchini, G., Bianchetti, R. Biochim. Biophys. Acta (1980) [Pubmed]
  9. A mutated murine reduced folate carrier (RFC1) with increased affinity for folic acid, decreased affinity for methotrexate, and an obligatory anion requirement for transport function. Zhao, R., Assaraf, Y.G., Goldman, I.D. J. Biol. Chem. (1998) [Pubmed]
  10. Discrimination among reduced folates and methotrexate as transport substrates by a phenylalanine substitution for serine within the predicted eighth transmembrane domain of the reduced folate carrier. Zhao, R., Gao, F., Goldman, I.D. Biochem. Pharmacol. (1999) [Pubmed]
  11. Purification and characterization of folate binding proteins from rat placenta. da Costa, M., Rothenberg, S.P. Biochim. Biophys. Acta (1996) [Pubmed]
  12. Molecular events in the membrane transport of methotrexate in human CCRF-CEM leukemia cell lines. Freisheim, J.H., Ratnam, M., McAlinden, T.P., Prasad, K.M., Williams, F.E., Westerhof, G.R., Schornagel, J.H., Jansen, G. Adv. Enzyme Regul. (1992) [Pubmed]
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