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A histochemical method for dihydrofolate reductase

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A histochemical method for the detection of dihydrofolate reductase (5,6,7,8-tetrahydrofolate: NADP oxidoreductase, E.C. 1.5.1.3) is described. With this method, the highest enzyme activity has been found in hepatocytes, nephrocytes, intestinal epithelium and connective tissue cells. In myocardial and skeletal muscle fibres and in leukocytes, the activity was of medium intensity, whereas neurons exhibited no activity.

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References

  • Bertino, J. R. (1963). The mechanism of action of the folate antagonists in man.Cancer Res. 23, 1286–306.

    Google Scholar 

  • Bertino, J. R., Gabrio, B. W. &Huennekens, F. M. (1960). Dihydrofolate reductase in human leukemic leukocytes.Biochem. biophys. Res. Commun. 3, 461–5.

    Google Scholar 

  • Bertino, J. R., Silber, R., Freeman, M., Alenty, A., Albrecht, M., Gabrio, B. W. &Huennekens, F. M. (1963). Studies on normal and leukemic leukocytes. IV. Tetrahydrofolate-dependent enzyme systems and dihydrofolicreductase.J. clin. Invest. 42, 1899–907.

    Google Scholar 

  • Blakley, R. L. &Mcdougall, B. M. (1961). Dihydrofolic acid reductase from Streptococcus faecalis.J. biol. Chem. 236, 1163.

    Google Scholar 

  • Carney, M. W. P. (1967). Serum folate values in 423 psychiatric pateints.Br. med. J. 4, 512–16.

    Google Scholar 

  • Diculescu, I. &Onicescu, D. (1965). La démonstration histochimique des epimérases de l'acide uridine diphospho-D-glucuronique.Histochemie 5, 450–2.

    Google Scholar 

  • Diculescu, I. &Onicescu, D. (1966). The histochemistry of epimerase. I. Uridine diphosphate glucuronic acid epimerase.Acta histochem. 25, 242–50.

    Google Scholar 

  • Finzi, A. F., Martelli, M., Tonato, M., Colonna, A. &Grignani, F. (1965). Gli enzimi tetraidrofolico dependenti e la diidrofolico reduttase nella epidermide umana normale e psoriasica e nelle neoplasie cutanee.Minerva Derm. 40, 449–56.

    Google Scholar 

  • Futterman, S. (1957). Enzymatic reduction of folic acid and dihydrofolic acid to tetrahydrofolic acid.J. biol. Chem. 228, 1031–8.

    Google Scholar 

  • Greenberg, D. M., Tam, B.-D., Jenny, E. &Payes, B. (1966). Highly purified dihydrofolate reductase of calf thymus.Biochim. biophys. Acta 122, 423–35.

    Google Scholar 

  • Grignani, F., Martelli, M., Tonato, M. &Colonna, A. (1965). Studies on the tetrahydrofolic acid dependent enzyme system in human leukocytes.Acta haemat. 34, 84–7.

    Google Scholar 

  • Grignani, F., Martelli, M. &Tonato, M. (1967a). Dihydrofolic reductase in human blood cells. II. Enzyme activity after amethopterin and actinomycin C administration.Enzymol. biol. clin. 8, 363–78.

    Google Scholar 

  • Grignani, F., Martelli, M., Tonato, M. &Finzi, A. F. (1967b). Folate dependent enzymes in human epidermis. II. Tetrahydrofolate dependent enzymes and relationship between amethopterin and dihydrofolic reductase.Archs Derm. (Chicago) 96, 577–85.

    Google Scholar 

  • Berbertv, Larrabee, A. R. &Buchanan, J. M. (1962). Studies on the identification of a folate compound of human serum.J. clin. Invest. 41, 1134.

    Google Scholar 

  • Hillcoat, B. L. &Blakley, R. L. (1966). Dihydrofolate reductase of Streptococcus faecalis. I. Purification and some properties of reductase from the wild strain and from strain A.J. biol. Chem. 241, 2995–3001.

    Google Scholar 

  • Hopwood, D. (1969). Fixatives and fixation: a review.Histochem. J. 1, 323–60.

    Google Scholar 

  • Huennekens, F. M. (1963). The role of dihydrofolic reductase in the metabolism of one carbon units.Biochemistry, N.Y. 2, 151–9.

    Google Scholar 

  • Kaufman, B. T. (1968). Studies on dihydrofolic reductase. III. Activation of the chicken liver enzyme by urea and thiourea.J. biol. Chem. 243, 6001–8.

    Google Scholar 

  • Kaufman, B. T. &Gardiner, C. R. (1966). Studies on dihydrofolate reductase. I. Purification and properties of dihydrofolate reductase from chicken liver.J. biol. Chem. 241, 1319–28.

    Google Scholar 

  • Kenkare, V. W. &Braganca, B. M. (1963). Flavin requirement and partial separation of enzymes catalysing the reduction of folic acid to tetrahydrofolic acid in liver.Biochem. J. 86, 160–6.

    Google Scholar 

  • Martelli, M., Tonato, M. &Grignani, F. (1967). Dihydrofolic reductase in human blood cells. I. Technique for the study of enzyme activity and intracellular amethopterin content.Enzymol. biol. clin. 8, 353–62.

    Google Scholar 

  • Mathews, C. K. &Huennekens, F. M. (1963). Further studies on dihydrofolic reductase.J. biol. Chem. 238, 2436–43.

    Google Scholar 

  • Morales, D. R. &Greenberg, D. M. (1964). Purification and properties of dihydrofolate reductase of sheep liver.Biochim. biophys. Acta 85, 360–76.

    Google Scholar 

  • Noronha, J. M. &Sreenivasan, A. (1960). In vitro conversion of pteroylglutamic acid to citrovorum factor by rat liver enzymes.Biochim. biophys. Acta 44, 64–71.

    Google Scholar 

  • Onicescu, D. (1967). On the histochemistry of epimerases. II. Hydroxyproline-2-epimerase.Histochemie 11, 180–4.

    Google Scholar 

  • Osborn, M. J. &Huennekens, F. M. (1958). Enzymatic reduction of dihydrofolic acid.J. biol. Chem. 233, 969.

    Google Scholar 

  • Pearse, A. G. E. (1968).Histochemistry, theoretical and applied, 3rd Ed., Vol. 1. London: Churchill.

    Google Scholar 

  • Piters, J. M. &Greenberg, D. M. (1958). Dihydrofolic acid reductase.J. Am. chem. Soc. 80, 6679.

    Google Scholar 

  • Rabinowitz, J. C. (1960). The folic acid. InThe Enzymes (eds. P. D. Boyer, H. Lardy and K. Myrback), Vol. 2, pp. 185–252. New York: Academic Press.

    Google Scholar 

  • Roberts, D. W. &Hall, T. C. (1965). Studies on folic reductase. II. Enzyme activity of embryonic organs of the chicken, rat and human.Cancer Res. 25, 1894–8.

    Google Scholar 

  • Robinson, F. A. (1966). The folic acid complex. In:The Vitamin Co-Factors of Enzyme-Systems, pp. 561–681. Oxford: Pergamon Press.

    Google Scholar 

  • Sirotnak, F. M. &Hutchison, D. J. (1966). Purification and properties of mutant and wild type of dihydrofolate reductase from Diplococcus pneumoniae.J. biol. Chem. 241, 2900–6.

    Google Scholar 

  • Smith, K., Scrimgeour, K. G. &Huennekens, F. M. (1963). Synthesis of a new form of dihydrofolate.Biochem. biophys. Res. Commun. 11, 388–92.

    Google Scholar 

  • Tonato, M., Martelli, M. F., Morettini, D. &Grignani, F. (1967). Tetrahydrofolate-dependent enzymes and dihydrofolic reductase in human tissue.Enzymol. biol. clin. 8, 209–14.

    Google Scholar 

  • Werkheiser, W. C., Zakrzewski, S. F. &Nichol, C. A. (1962). Assay for 4-amino folic acid analogues by inhibition of folic acid reductase.J. Pharmac. exp. Ther. 137, 162–6.

    Google Scholar 

  • Wilmanns, W. &Jaenicke, L. (1963). Die Bedeutung des Folsäure-Stoffwechsels für die normale und pathologische Reifung von Blutzellen.Klin. Wschr. 41, 1077–82.

    Google Scholar 

  • Zakrewski, S. F. (1960). Purification and properties of folic acid reductase from chicken liver.J. biol. Chem. 235, 1776–9.

    Google Scholar 

  • Zakrzewski, S. F. &Nichol, C. A. (1958). On the enzymic reduction of folic acid by a purified hydrogenase.Biochim. biophys. Acta 27, 425–6.

    Google Scholar 

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Onicescu, D., Taşcâ, L. & Trutza, E. A histochemical method for dihydrofolate reductase. Histochem J 2, 289–295 (1970). https://doi.org/10.1007/BF01004997

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  • DOI: https://doi.org/10.1007/BF01004997

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