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Genetic Aspects of Folate Metabolism

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Advances in Human Genetics 9

Part of the book series: Advances in Human Genetics ((AHUG,volume 9))

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Abstract

Folic acid is an essential vitamin required for important steps in the synthesis of purines and pyrimidines, and in amino acid metabolism. Humans, in contrast to plants, bacteria, and yeast, are unable to synthesize folates de novo and thus depend on an adequate dietary supply of folates to the extent of at least 50 µg/day for nonpregnant adults (Herbert, 1971). Moreover, normal function requires that these dietary folates be properly absorbed, distributed throughout the organism, and used by cells.

An erratum to this chapter is available at http://dx.doi.org/10.1007/978-1-4615-8276-2_8

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References

  • Abelson, H. T., Fosburg, M., Gorka, C., and Komblith, P., 1978, Identification of dihy-drofolate reductase in human central-nervous-system tumours, Lancet 1:184–185.

    CAS  PubMed  Google Scholar 

  • Akamatsu, Y., and Law, J. H., 1970, The enzymatic synthesis of fatty acid methyl esters by carboxyl group alkylation, J. Biol. Chem. 245:709–713.

    CAS  PubMed  Google Scholar 

  • Albrecht, A. M., Biedler, J. L., and Hutchison, D. J., 1972, Two different species of dihydrofolate reductase in mammalian cells differentially resistant to amethopterin and methasquin, Cancer Res. 32:1539–1546.

    CAS  PubMed  Google Scholar 

  • Allen, R. H., 1976, The plasma transport of vitamin B12, Br. J. Haematol. 33:161–171.

    CAS  PubMed  Google Scholar 

  • Alperin, J. B., and Haggard, M. E., 1970, Cerebrospinal fluid folate (CFA) and the blood-brain barrier, Clin. Res. 18:40.

    Google Scholar 

  • Alt, F. W., Kellems, R. E., and Schmike, R. T., 1976, Synthesis and degradation of folate reductase in sensitive and methotrexate-resistant lines of S-180 cells, J. Biol Chem. 251:3063–3074.

    CAS  PubMed  Google Scholar 

  • Alt, F. W., Kellems, R. E., Bertino, J. R., and Schimke, R. T., 1978, Selective multiplication of dihydrofolate reductase genes in methotrexate-resistant variant of cultured murine cells, J. Biol. Chem. 253:1357–1370.

    CAS  PubMed  Google Scholar 

  • Antun, F. T., Burnett, G. B., Cooper, A. J., Daly, R. J., Smythies, J. R., and Zealley, A. K., 1971, The effects of L-methionine (without MAOI) in schizophrenia, J. Psychiatr. Res. 8:63–71.

    CAS  PubMed  Google Scholar 

  • Arakawa, T., 1970, Congenital defects in folate utilization, Am. J. Med. 48:594–598.

    CAS  PubMed  Google Scholar 

  • Arakawa, T., and Wada, Y., 1966, Urinary AICA (4-amino-5-imidazolecarboxamide) following an oral dose of AICA in formiminotransferase deficiency syndrome, Tohoku J. Exp. Med. 88:99–102.

    CAS  PubMed  Google Scholar 

  • Arakawa, T., Ohara, K., Kudo, Z., Tada, K., Hayashi, T., and Mizuno, T., 1963, “Hyperfolic-acidemia with formiminoglutamic-aciduria following histidine loading”: Suggested for a case of congenital deficiency in formiminotransferase, Tohoku J. Exp. Med. 80:370–382.

    CAS  PubMed  Google Scholar 

  • Arakawa, T., Ohara, K., Takahashi, Y., Ogasawara, J., Hayashi, T., Chiba, R., Wada, Y., Tada, K., Mizuno, T., Okamura, T., and Yoshida, T., 1965, Formiminotransferase-deficiency syndrome: A new inborn error of folic acid metabolism, Ann. Paediatr. 205:1–11.

    CAS  PubMed  Google Scholar 

  • Arakawa, T., Fujii, M., and Hirono, H., 1966a, Tetrahydrofolate-dependent enzyme activities of erythrocytes in formiminotransferase deficiency syndrome, Tohoku J. Exp. Med. 88:305–310.

    CAS  PubMed  Google Scholar 

  • Arakawa, T., Fujii, M., and Ohara, K., 1966b, Erythrocyte formiminotransferase activity in formiminotransferase deficiency syndrome, Tohoku J. Exp. Med. 88:195–202.

    CAS  PubMed  Google Scholar 

  • Arakawa, T., Fujii, M., Ohara, K., Watanabe, S., Karahashi, M., Koboyashi, M., and Hirono, H., 1966c, Mental retardation with hyperfolic-acidemia not associated with formiminoglutamic-aciduria: Cyclohydrolase deficiency syndrome, Tohoku J. Exp. Med. 88:341–352.

    CAS  PubMed  Google Scholar 

  • Arakawa, T., Narisawa, K., Tanno, K., Ohara, K., Higashi, O., Hondo, Y., Tamura, T., Wada, Y., Mizuno, T., and Hayashi, R., 1967, Megaloblastic anaemia and mental retardation associated with hyperfolic-aciduria: Probably due to N 5 methyltetrahydro-folate transferase deficiency, Tohoku J. Exp. Med. 93:1–22.

    CAS  PubMed  Google Scholar 

  • Arakawa, T., Tamura, T., Higashi, O., Ohara, K., Tanno, K., Honda, Y., Narisawa, K., Konno, T., Wada, Y., Sato, Y., and Mizuno, T., 1968a, Tohoku J. Exp. Med. 94:3–16.

    CAS  PubMed  Google Scholar 

  • Arakawa, T., Tamura, T., Ohara, K., Narisawa, K., Tanno, K., Hondo, Y., and Higashi, O., 1968b, Familial occurrence of formiminotransferase deficiency syndrome, Tohoku J.Exp. Med. 96:211–217.

    CAS  PubMed  Google Scholar 

  • Arakawa, T., Yoshida, T., Konno, T., and Honda, Y., 1972, Defect of incorporation of glycine-1–14C into urinary uric acid in formiminotransferase deficiency syndrome, Tohoku J. Exp. Med. 106:213–218.

    CAS  PubMed  Google Scholar 

  • Baldessarini, R. J., 1966, Alterations in tissue levels of S-adenosylmethionine, Biochem. Pharmacol. 15:741–748.

    CAS  PubMed  Google Scholar 

  • Baskin, F., Carlin, S. C., Kraus, P., Friedkin, M., and Rosenberg, R. N., 1975, Experimental chemotherapy of neuroblastoma. II. Increased thymidylate synthetase activity in a 5-fluorodeoxyuridine-resistant variant of mouse neuroblastoma, Mol. Pharmacol. 11:105–117.

    CAS  PubMed  Google Scholar 

  • Baugh, C. M., Krumdieck, C. L., Baker, H. J., and Butterworth, C. E., Jr., 1971, Studies on the absorption and metabolism of folic acid. I. Folate absorption in the dog after exposure of isolated intestinal segments to synthetic pteroylpolyglutamates of various chain lengths, J. Clin. Invest. 50:2009–2021.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Baugh, C. M., Krumdieck, C. L., and Nair, M. G., 1973, Polyglutamyl metabolites of methotrexate, Biochem. Biophys. Res. Commun. 52:27–34.

    CAS  PubMed  Google Scholar 

  • Baumgartner, E. R., Schweizer, K., and Wick, H., 1977, Different congenital forms of defective remethylation in homocystinuria: Clinical, biochemical and morphologic studies, Pediatr. Res. 11:1015.

    Google Scholar 

  • Beaudet, R., and MacKenzie, R. E., 1976, Formiminotransferase • cyclodeaminase from porcine liver: An octomeric enzyme containing bifunctional polypeptides, Biochim. Biophys. Acta 453:151–161.

    CAS  PubMed  Google Scholar 

  • Biedler, J. L., and Spengler, B. A., 1976a, Metaphase chromosome anomaly: Association with drug resistance and cell specific products, Science 191:185–187.

    CAS  PubMed  Google Scholar 

  • Biedler, J. L., and Spengler, B. A., 1976b, Quantitative relationships between a chromosome abnormality (HSR) and antifolate resistance associated with enzyme overproduction, J. Cell Biol. 70:117a.

    Google Scholar 

  • Blakley, R. H., 1969, The Biochemistry of Folic Acid and Related Pteridines, American Elsevier, New York, 569 pp.

    Google Scholar 

  • Branda, R. F., Anthony, B. K., and Jacob, H. S., 1978, The mechanism of 5-methylte-trahydrofolate transport by human erythrocytes, J. Clin. Invest. 61:1270–1275.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Brewster, T. G., Abroms, I. F., Kaufman, S., Breslow, J. L., Moskowitz, M. A., Villee, D. B., and Snodgrass, R. S., 1976, Atypical PKU, seizures, and developmental delay with dihydropteridine reductase deficiency, Pediatr. Res. 10:446.

    Google Scholar 

  • Broderick, D. S., North, J. A., and Mangum, J. H., 1972, Isolation of N 5, N 10-methylene tetrahydrofolate reductase from bovine brain, Prep. Biochem. 2:207–214.

    CAS  PubMed  Google Scholar 

  • Brody, T., Shin, Y. S., and Stokstad, E. L. R., 1976, Rat brain folate indentification, J. Neurochem. 27:409–413.

    CAS  PubMed  Google Scholar 

  • Brown, J. H., and Allison, J. B., 1948, Effects of excess dietary dl-methionine and/or l-arginine on rats, Proc. Soc. Exp. Biol. Med. 69:196–198.

    CAS  PubMed  Google Scholar 

  • Buchanan, J. M., Elford, H. L., Loughlin, R. E., McDougall, B. M., and Rosenthal, S.,

    Google Scholar 

  • 1964, The role of vitamin B12 in methyl transfer to homocysteine, Ann. N. Y. Acad. Sci. 112:756–773.

    Google Scholar 

  • Buchanan, N., Geefhuysen, J., Cassel, R., and Green, R., 1973, Selective malabsorption of vitamin B12 in a Negro boy, Scand. J. Haematol. 11:153–157.

    CAS  PubMed  Google Scholar 

  • Burton, E. G., and Sallach, H. J., 1975, Methylenetetrahydrofolate reductase in the rat central nervous system: Intracellular and regional distribution, Arch. Biochem. Biophys. 166:483–494.

    CAS  PubMed  Google Scholar 

  • Butler, I. J., Koslow, S. H., Krumholz, A., Holtzman, N. A., and Kaufman, S., 1978, A disorder of biogenic amines in dihydropteridine reductase deficiency, Ann. Neurol. 3:224–230.

    CAS  PubMed  Google Scholar 

  • Caboche, M., 1976, Methionine metabolism in BHK cells: Selection and characterization of ethionine resistant clones, J. Cell Physiol. 87:321–336.

    CAS  PubMed  Google Scholar 

  • Chan, C., Shin, Y., and Stokstad, E. L. R., 1973, Studies of folic acid compounds in nature. III. Folic acid compounds in cabbage, Can. J. Biochem. 51:1617–1623.

    CAS  PubMed  Google Scholar 

  • Chanarin, I., 1963, Urocanic acid and formimino-glutamic acid excretion in megaloblastic anaemia and other conditions: The effect of specific therapy, Br. J. Haematol. 9:141–157.

    CAS  PubMed  Google Scholar 

  • Chanarin, I., Mollin, D. L., and Anderson, B. B., 1958, The clearance from the plasma of folic acid injected intravenously in normal subjects and patients with megaloblastic anaemia, Br. J. Haematol. 4:435–446.

    CAS  PubMed  Google Scholar 

  • Chanarin, I., Perry, J., and Lumb, M., 1974, The biochemical lesion in vitamin-B12 deficiency in man, Lancet 1:1251–1252.

    CAS  PubMed  Google Scholar 

  • Chang, S. E., and Littlefield, J. W., 1976, Elevated dihydrofolate reductase messenger RNA levels in methotrexate-resistant BHK cells, Cell 7:391–396.

    CAS  PubMed  Google Scholar 

  • Chasin, L. A., Feldman, A., Konstam, M., and Urlaub, G., 1974, Reversion of a Chinese hamster cell auxotrophic mutant, Proc. Natl. Acad. Sci. U.S.A. 71:718–722.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chen, C.-P., and Wagner, C., 1975, Folate transport in the choroid plexus, Life Sci. 16:1571–1582.

    CAS  PubMed  Google Scholar 

  • Cheng, F. W., Shane, B., and Stokstad, E. L. R., 1975, Pentaglutamate derivatives of folate as substrates for rat liver tetrahydropteroylglutamate methyltransferase and 5,10-methylenetetrahydrofolate reductase, Can. J. Biochem. 53:1020–1027.

    CAS  Google Scholar 

  • Chiao, F. F., and Stokstad, E. L. R., 1977, Effect of methionine on hepatic folate metabolism in rats fed a vitamin B12- and methionine-deficient diet, Proc. Soc. Exp. Biol. Med. 155:433–437.

    CAS  PubMed  Google Scholar 

  • Conrad, A. H., and Ruddle, F. H., 1972, Regulation of thymidylate synthetase activity in cultured mammalian cells, J. Cell Sci. 10:471–486.

    CAS  PubMed  Google Scholar 

  • Cooper, B. A., and Lowenstein, L., 1964, Relative folate deficiency of erythrocytes in pernicious anemia and its correction by cyanocobalamin, Blood 24:502–521.

    CAS  PubMed  Google Scholar 

  • Cooper, B. A., and Rosenblatt, D., 1976, Folate coenzyme forms in fibroblasts from patients deficient in 5,10-methylenetetrahydrofolate reductase, Biochem. Soc. Trans. 4:921–922.

    CAS  PubMed  Google Scholar 

  • Corcino, S. S., Waxman, S., and Herbert, V., 1971, Uptake of tritiated folates by human bone marrow cells in vitro, Br. J. Haematol. 20:503–509.

    CAS  Google Scholar 

  • Coward, J. K., D’Urso-Scott, M., and Sweet, W. D., 1972, Inhibition of catechol-O-methyltransferase by 5-adenosylhomocysteine and 5-adenosylhomocysteine sulfoxide, a potential transition-state analogue, Biochem. Pharmacol. 21:1200–1203.

    CAS  PubMed  Google Scholar 

  • Coward, J. K., Parameswaran, K. N., Cashmore, A. R., and Bertino, J. R., 1974, 7,8-Dihydropteroyl oligo-γ-L-glutamates: Synthesis and kinetic studies with purified dihydrofolate reductase from mammalian sources, Biochemistry 13:3899–3903.

    CAS  PubMed  Google Scholar 

  • Coward, J. K., Chello, P. L., Cashmore, A. R., Parameswaran, K. N., DeAngelis, L. M., and Bertino, J. R., 1975, 5-Methyl-5,6,7,8-tetrahydropteroyl oligo-γ-L-glutamates: Synthesis and kinetic studies with methionine synthetase from bovine brain, Biochemistry 14:1548–1552.

    CAS  PubMed  Google Scholar 

  • Curthoys, N. P., and Rabinowitz, J. C., 1972, Formyltetrahydrofolate synthetase: Binding of folate substrates and kinetics of the reverse reaction, J. Biol. Chem. 247:1965–1971.

    CAS  PubMed  Google Scholar 

  • da Costa, M., and Rothenberg, S. P., 1976, Studies with the folate binding protein in chronic granulocytic leukaemia cells. I. Synthesis and release of binder by cells in short-term culture, Br. J. Haematol. 34:581–587.

    PubMed  Google Scholar 

  • Das, K. C., and Hoffbrand, A. V., 1970, Studies of folate uptake by phytohaemagglutinin-stimulated lymphocytes, Br. J. Haematol. 19:203–221.

    CAS  PubMed  Google Scholar 

  • Dayan, A. D., and Ramsey, R. B., 1974, An inborn error of vitamin B12 metabolism associated with cellular deficiency of coenzyme forms of the vitamin, J. Neurol. Sci. 23:117–128.

    CAS  PubMed  Google Scholar 

  • Deguchi, T., and Barchas, J., 1971, Inhibition of transmethylations of biogenic amines by S-adenosylhomocysteine: Enhancement of transmethylation by adenosylhomocysteinase, J. Biol. Chem. 246:3175–3181.

    CAS  PubMed  Google Scholar 

  • Dickerman, H. W., Redfield, B. G., Bieri, J. G., and Weissbach, H., 1964a, Studies on the role of vitamin B12 for the synthesis of methionine in liver, Ann. N. Y. Acad. Sci. 112:791–798.

    CAS  PubMed  Google Scholar 

  • Dickerman, H., Redfield, B. G., Bieri, J. G., and Weissbach, H., 1964b, The role of vitamin B12 in methionine biosynthesis in avian liver, J. Biol. Chem. 239:2545–2552.

    CAS  PubMed  Google Scholar 

  • Dillon, M. J., England, J. ML, Gompertz, D., Goodey, P. A., Grant, D. B., Hussein, H. A.-A., Linnell, J. C., Matthews, D. M., Mudd, S. H., Newns, G. H., Seakins, J. W. T., Uhlendorf, B. W., and Wise, I. J., 1974, Mental retardation, megaloblastic anaemia, methylmalonic aciduria and abnormal homocysteine metabolism due to an error in vitamin B12 metabolism, Clin. Sci. Mol. Med. 47:43–61.

    CAS  PubMed  Google Scholar 

  • Dolnick, B. J., and Cheng, Y.-C., 1978, Human thymidylate synthetase. II. Derivatives of pteroylmono- and -polyglutamates as substrates and inhibitors, J. Biol. Chem. 253:3563–3567.

    CAS  PubMed  Google Scholar 

  • Donaldson, K. O., and Keresztesy, J. C., 1962, Naturally occurring forms of folic acid. II. Enzymatic conversion of methylenetetrahydrofolic acid to prefolic A-methyltetrahy-drofolate, J. Biol. Chem. 237:1298–1304.

    CAS  PubMed  Google Scholar 

  • Erbe, R. W., 1975, Inborn errors of folate metabolism, N. Engl. J. Med. 293:753–758, 807–811.

    CAS  PubMed  Google Scholar 

  • Finkelstein, J. D., and Mudd, S. H., 1967, Trans-sulfuration in mammals: The methionine-sparing effect of cystine, J. Biol. Chem. 242:873–880.

    CAS  PubMed  Google Scholar 

  • Finkelstein, J. D., Kyle, W. E., and Harris, B. J., 1971, Methionine metabolism in mammals: Regulation of homocysteine methyltransferases in rat tissue, Arch. Biochem. Biophys. 146:84–92.

    CAS  PubMed  Google Scholar 

  • Finkelstein, J. D., Kyle, W. E., and Martin, J. J., 1975, Abnormal methionine adenosyl-transferase in hypermethioninemia, Biochem. Biophys. Res. Commun. 66:1491–1497.

    CAS  PubMed  Google Scholar 

  • Fischer, C. D., da Costa, M., and Rothenberg, S. P., 1975, The heterogeneity and properties of folate binding proteins from chronic myelogenous leukemia cells, Blood 46:855–867.

    CAS  PubMed  Google Scholar 

  • Fischer, G. A., 1961, Increased levels of folic acid reductase as a mechanism of resistance to amethopterin in leukemic cells, Biochem. Pharmacol. 7:75–77.

    CAS  PubMed  Google Scholar 

  • Fischer, G. A., 1962, Defective transport of amethopterin (methotrexate) as a mechanism of resistance to the antimetabolite in L5178Y leukemic cells, Biochem. Pharmacol. 11:1233–1234.

    CAS  PubMed  Google Scholar 

  • Flaks, J. G., Erwin, M. J., and Buchanan, J. M., 1957, Biosynthesis of purines. XVIII. 5-Amino-l-ribosyl-4-imidazolecarboxamide 5′-phosphate transformylase and inosinicase, J. Biol. Chem. 229:603–612.

    CAS  PubMed  Google Scholar 

  • Flintoff, W. F., Davidson, S. V., and Siminovitch, L., 1976a, Isolation and partial characterization of three methotrexate-resistant phenotypes from Chinese hamster ovary cells, Somatic Cell Genet. 2:245–261.

    CAS  PubMed  Google Scholar 

  • Flintoff, W. F., Spindler, S. M., and Siminovitch, L., 1976b, Genetic characterization of methotrexate-resistant Chinese hamster ovary cells, In Vitro 12:749–757.

    CAS  PubMed  Google Scholar 

  • Freeman, J. M., Finkelstein, J. D., and Mudd, S. H., 1975, Folate-responsive homocystinuria and “schizophrenia”: A defect in methylation due to deficient 5,10-methylenete-trahydrofolate reductase activity, N. Engl. J. Med. 292:491–496.

    CAS  PubMed  Google Scholar 

  • Friedkin, M., 1973, Thymidylate synthetase, Adv. Enzymol. 38:235–292.

    CAS  PubMed  Google Scholar 

  • Friedkin, M., Crawford, E., Humphreys, S. R., and Goldin, A., 1962, The association of increased dihydrofolate reductase with amethopterin resistance in mouse leukemia, Cancer Res. 22:600–606.

    CAS  PubMed  Google Scholar 

  • Friedman, P. A., Kappelman, A. H., and Kaufman, S., 1972, Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain, J. Biol. Chem. 247:4165–4173.

    CAS  PubMed  Google Scholar 

  • Friedmann, B., Nakada, H. I., and Weinhouse, S., 1954, A study of the oxidation of formic acid in the folic acid-deficient rat, J. Biol. Chem. 210:413–421.

    CAS  PubMed  Google Scholar 

  • Furuhjelm, U., and Nevanlinna, H. R., 1973, Inheritance of selective malabsorption of vitamin B12, Scand. J. Haematol. 11:27–34.

    CAS  PubMed  Google Scholar 

  • Gaull, G. E., 1975, Methionine adenosyltransferase: Development and deficiency in the human, in: Normal and Pathological Development of Energy Metabolism (F. A. Hommes and C. J. Van den Berg, eds.), pp. 11–23, Academic Press, London.

    Google Scholar 

  • Gaull, G. E., and Tallan, H. H., 1974, Methionine adenosyltransferase deficiency: New enzymatic defect associated with hypermethioninemia, Science 186:59–60.

    CAS  PubMed  Google Scholar 

  • Gaull, G. E., von Berg, W., Räihä, N. C. R., and Sturman, J. A., 1973, Development of methyltransferase activities in human fetal tissues, Pediatr. Res. 7:527–533.

    CAS  PubMed  Google Scholar 

  • Ghitis, J., 1967, The folate binding in milk, Am. J. Clin. Nutr. 20:1–4.

    CAS  PubMed  Google Scholar 

  • Goldman, I. D., 1971, The characteristics of the membrane transport of amethopterin and the naturally occuring folates, Ann. N. Y. Acad. Sci. 186:400–422.

    CAS  PubMed  Google Scholar 

  • Goodman, S. I., Moe, P. G., and Hammond, K. B., 1970, Homocystinuria with methylmalonic aciduria: Two cases in a sibship, Biochem. Med. 4:500–515.

    CAS  PubMed  Google Scholar 

  • Gräsbeck, R., 1972, Familial selective vitamin B12 malabsorption, N. Engl. J. Med. 287:358.

    PubMed  Google Scholar 

  • Gräsbeck, R., Gordin, R., Kantero, I., and Kuhlbäck, B., 1960, Selective vitamin B12 malabsorption and proteinuria in young people: A syndrome, Acta Med. Scand. 167:289–296.

    PubMed  Google Scholar 

  • Guest, J. R, Friedman, S., Foster, M. A., Tejerina, G., and Woods, D. D., 1964, Transfer of the methyl group from N 5-methyltetrahydrofolates to homocysteine in Escherichia coli, Biochem. J. 92:497–504.

    CAS  Google Scholar 

  • Hakala, M. T., Zakrzewski, S. F., and Nichol, C. A., 1961, Relation of folic acid reductase to amethopterin resistance in cultured mammalian cells, J. Biol. Chem. 236:952–958.

    CAS  PubMed  Google Scholar 

  • Hakami, N., Neiman, P. E., Canellos, G. P., and Lazerson, J., 1971, Neonatal megaloblastic anemia due to inherited transcobalamin II deficiency in two siblings, N. Engl. J. Med. 285:1163–1170.

    CAS  PubMed  Google Scholar 

  • Hall, C. A., 1975, Transcobalamins I and II as natural transport proteins of vitamin B12, J. Clin. Invest. 56:1125–1131.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hänggi, U. J., and Littlefield, J. W., 1974, Isolation and characterization of the multiple forms of dihydrofolate reductase from methotrexate-resistant cells, J. Biol. Chem. 249:1390–1397.

    PubMed  Google Scholar 

  • Hänggi, U. J., and Littlefield, J. W., 1976, Altered regulation of the rate of synthesis of dihydrofolate reductase in methotrexate-resistant hamster cells, J. Biol. Chem. 251:3075–3080.

    PubMed  Google Scholar 

  • Harris, H., 1963, Garrod’s Inborn Errors of Metabolism, Oxford University Press, London, 207 pp.

    Google Scholar 

  • Hartman, S. C., and Buchanan, J. M., 1959, Biosynthesis of the purines. XXVI. The identification of the formyl donors of the transformylation reactions, J. Biol. Chem. 234:1812–1816.

    CAS  PubMed  Google Scholar 

  • Herbert, V., 1971, Predicting nutrient deficiency by formula, N. Engl. J. Med. 284:976–977.

    CAS  PubMed  Google Scholar 

  • Herbert, V., and Sullivan, L. W., 1963, Formiminoglutamicaciduria in humans with megaloblastic anemia: Diminution by methionine or glycine, Proc. Soc. Exp. Biol. Med. 112:304–305.

    CAS  PubMed  Google Scholar 

  • Herbert, V., and Zalusky, R., 1962, Interrelations of vitamin B12 and folic acid metabolism: Folic acid clearance studies, J. Clin. Invest. 41:1263–1276.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Herbert, V., Larrabee, A. R., and Buchanan, J. R., 1962, Studies on the identification of a folate compound in human serum, J. Clin. Invest. 41:1134–1138.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Herman, R. H., Rosensweig, N. S., Stifel, F. B., and Herman, Y. F., 1969, Adult formiminotransferase deficiency: A new entity, Clin. Res. 17:304.

    Google Scholar 

  • Hitzig, W. H., Dohmann, U., Pluss, H. J., and Vischer, D., 1974, Hereditary transcobalamin II deficiency: Clinical findings in a new family, J. Pediatr. 85:622–628.

    CAS  PubMed  Google Scholar 

  • Hoffbrand, A. V., Tripp, E., and Lavoie, A., 1976, Synthesis of folate polyglutamates in human cells, Clin. Sci. Mol. Med. 50:61–68.

    CAS  PubMed  Google Scholar 

  • Hoffman, R. M., and Erbe, R. W., 1974, Regulation of folates in proliferating and quiescent human fibroblasts, J. Cell Biol. 63:141a.

    Google Scholar 

  • Hoffman, R.M., and Erbe, R.W., 1976, High in vivo rates of methionine biosynthesis in transformed human and malignant rat cells auxotrophic for methionine, Proc. Natl. Acad. Sci. U.S.A. 73:1523–1527.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Home, D. W., Briggs, W. T., and Wagner, C., 1978, Transport of 5-methyltetrahydrofolic acid and folic acid in freshly isolated hepatocytes, J. Biol. Chem. 253:3529–3535.

    Google Scholar 

  • Hsu, L. L., and Mandell, A. J., 1975, Methylene-β-phenylethylimine formation from 5-methyltetrahydrofolic acid and β-phenylethylamine, Life Sci. 17:387–396.

    CAS  PubMed  Google Scholar 

  • Huennekens, F. M., Hatefi, Y., and Kay, L. D., 1957, Manometric assay and cofactor requirements for serine hydroxymethylase, J. Biol. Chem. 224:435–444.

    CAS  PubMed  Google Scholar 

  • Imerslund, O., 1960, Idiopathic chronic megaloblastic anemia in children, Acta Paediatr. Suppl. 119:1–115.

    Google Scholar 

  • Jackson, R. C., Hart, L. I., and Harrap, K. R., 1976, Intrinsic resistance to methotrexate of cultured mammalian cells in relation to the inhibition kinetics of their dihydrofolate reductases, Cancer Res. 36:1991–1997.

    CAS  PubMed  Google Scholar 

  • Jeejeebhoy, K. N., Pathare, S. M., and Noronha, J. M., 1965, Observations on conjugated and unconjugated blood folate levels in megaloblastic anemia and the effects of vitamin B12, Blood 26:354–359.

    CAS  PubMed  Google Scholar 

  • Kamely, D., Littlefield, J. W., and Erbe, R. W., 1973, Regulation of 5-methyltetrahydro-folate:homocysteine methyltransferase activity by methionine, vitamin B12, and folate in cultured baby hamster kidney cells, Proc. Natl. Acad. Sci. U.S.A. 70:2585–2589.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kamen, B. A., and Caston, J. D., 1975, Identification of a folate binder in hog kidney, J. Biol. Chem. 250:2203–2205.

    CAS  PubMed  Google Scholar 

  • Kanwar, Y. S., Manaligod, J. R., and Wong, P. W. K., 1976, Morphologic studies in a patient with homocystinuria due to 5,10-methylenetetrahydrofolate reductase deficiency, Pediatr. Res. 10:598–609.

    CAS  PubMed  Google Scholar 

  • Kao, F.-T., and Puck, T. T., 1968, Genetics of somatic mammalian cells. VII. Induction and isolation of nutritional mutants in Chinese hamster cells, Proc. Natl. Acad. Sci. U.S.A. 60:1275–1281.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kaufman, S., 1967, Metabolism of the phenylalanine hydroxylation cofactor, J. Biol. Chem. 242:3934–3943.

    CAS  PubMed  Google Scholar 

  • Kaufman, S., Holtzman, N. A., Milstien, S., Butler, I. J., and Krumholz, A., 1975, Phenylketonuria due to a deficiency of dihydropteridine reductase, N. Engl. J. Med. 293:785–790.

    CAS  PubMed  Google Scholar 

  • Kaufman, S., Berlow, S., Summer, G. K., Milstien, S., Schulman, J. D., Orloff, S., Spielberg, S., and Pueschel, S., 1978, Hyperphenylalaninemia due to a deficiency of biopterin: A variant form of phenylketonuria, N. Engl. J. Med. 299:673–679.

    CAS  PubMed  Google Scholar 

  • Kellems, R. E., Alt, F. W., and Schimke, R. T., 1976, Regulation of folate reductase synthesis in sensitive and methotrexate-resistant sarcoma 180 cells, J. Biol. Chem. 251:6987–6993.

    CAS  PubMed  Google Scholar 

  • Kerwar, S. S., Spears, C., McAuslan, B., and Weissbach, H., 1971, Studies on vitamin B12 metabolism in HeLa cells, Arch. Biochem. Biophys. 142:231–237.

    CAS  PubMed  Google Scholar 

  • Killman, S.-A., 1964, Effect of deoxyuridine on incorporation of tritiated thymidine: Difference between normoblasts and megaloblasts, Acta Med. Scand. 175:483–488.

    Google Scholar 

  • Klain, G. J., Vaughan, D. A., and Vaughan, L. N., 1963, Some metabolic effects of methionine toxicity in the rat, J. Nutr. 80:337–341.

    CAS  PubMed  Google Scholar 

  • Klavins, J. V., Kinney, T. D., and Kaufman, N., 1963, Histopathologic changes in methionine excess, Arch. Pathol. 75:661–673.

    CAS  PubMed  Google Scholar 

  • Kolhouse, J. F., and Allen, R. H., 1977, Recognition of two intracellular cobalamin binding proteins and their identification as methylmalonyl-CoA mutase and methionine synthetase, Proc. Natl. Acad. Sci. U.S.A. 74:921–925.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Koslow, S. H., and Butler, I. J., 1977, Biogenic amine synthesis defect in dihydropteridine reductase deficiency, Science 198:522–523.

    CAS  PubMed  Google Scholar 

  • Krebs, H. A., Hems, R., and Tyler, B., 1976, The regulation of folate and methionine metabolism, Biochem. J. 158:341–353.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kutzbach, C., and Stokstad, E. L. R., 1967, Feedback inhibition of methylenetetrahydro-folate reductase in rat liver by S-adenosylmethionine, Biochim. Biophys. Acta 139:217–220.

    CAS  PubMed  Google Scholar 

  • Kutzbach, C., and Stokstad, E. L. R., 1971, Mammalian methylenetetrahydrofolate reductase: Partial purification, properties, and inhibition by S-adenosylmethionine, Biochim. Biophys. Acta 250:459–477.

    CAS  PubMed  Google Scholar 

  • Kutzbach, C., Galloway, E., and Stokstad, E. L. R., 1967, Influence of vitamin B12 and methionine on levels of folic acid compounds and folate enzymes in rat liver, Proc. Soc. Exp. Biol. Med. 124:801–805.

    CAS  PubMed  Google Scholar 

  • La Du, B. N., 1978, Histidinemia, in: The Metabolic Basis of Inherited Disease (J. B. Stanbury, J. B. Wyngaarden, and D. S. Fredrickson, eds.), pp. 317–327, McGraw-Hill, New York.

    Google Scholar 

  • La Du, B. N., Howell, R. R., Jacoby, G. A., Seegmiller, J. E., and Zannoni, V. G., 1962, The enzymatic defect in histidinemia, Biochem. Biophys. Res. Commun. 7:398–402.

    Google Scholar 

  • Laduron, P., 1972, N-methylation of dopamine to epinine in brain tissue using N-methyl-tetrahydrofolic acid as the methyl donor, Nature (London) New Biol. 238:212–213.

    CAS  Google Scholar 

  • Lanzkowsky, P., 1970, Congenital malabsorption of folate, Am. J. Med. 48:580–583.

    CAS  PubMed  Google Scholar 

  • Lanzkowsky, P., Erlandson, M. E., and Bezan, A. I., 1969, Isolated defect of folic acid absorption associated with mental retardation and cerebral calcification, Blood 34:452–465.

    CAS  PubMed  Google Scholar 

  • Lavoie, A., Tripp, E., Hoffbrand, A. V., 1974, The effect of vitamin B12 deficiency on methylfolate metabolism and pteroylpolyglutamate synthesis in human cells, Clin. Sci. Mol. Med. 47:617–630.

    CAS  PubMed  Google Scholar 

  • Levitt, M., Nixon, P. F., Pincus, J. H., and Bertino, J. R., 1971, Transport characteristics of folates in cerebrospinal fluid; a study utilizing doubly labeled 5-methyltetrahydrofolate and 5-formyltetrahydrofolate, J. Clin. Invest. 50:1301–1308.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Levy, H. L., Mudd, S. H., Schulman, J. D., Dreyfus, P. M., and Abeles, R. M., 1970, A derangement in B12 metabolism associated with homocystinemia, cystathioninemia, hypomethioninemia and methylmalonic aciduria, Am. J. Med. 48:390–397.

    CAS  PubMed  Google Scholar 

  • Lin, R.-L., and Narasimhachari, N., 1974, Evidence for the absence of amine-N-methyl-ation and O-methylation in indolethylamines with methyltetrahydrofolic acid-dependent N-methyltransferase, Res. Commun. Chem. Pathol. Pharmacol. 8:535–542.

    CAS  PubMed  Google Scholar 

  • Linnell, J. C., Matthews, D. M., Mudd, S. H., Uhlendorf, B. W., and Wise, I. J., 1976, Cobalamins in fibroblasts cultured from normal control subjects and patients with methylmalonicaciduria, Pediatr. Res. 10:179–183.

    CAS  PubMed  Google Scholar 

  • Littlefield, J. W., 1964, Selection of hybrids from matings of fibroblasts in vitro and their presumed recombinants, Science 145:709–710.

    CAS  PubMed  Google Scholar 

  • Littlefield, J. W., 1969, Hybridization of hamster cells with high and low folate reductase activity, Proc. Natl. Acad. Sci. U.S.A. 62:88–95.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Luhby, A. L., and Cooperman, J. M., 1967, Congenital megaloblastic anemia and progressive central nervous system degeneration: Further clinical and physiological characterization and therapy of syndrome due to inborn error of folate transport, Proceedings of the American Pediatric Society, Atlantic City, April 26–29.

    Google Scholar 

  • Luhby, A. L., Eagle, F. J., Roth, E., and Cooperman, J. M., 1961, Relapsing megaloblastic anemia in an infant due to a specific defect in gastrointestinal absorption of folic acid, Am. J. Dis. Child. 102:482–483.

    Google Scholar 

  • Luhby, A. L., Cooperman, J. M., and Pesci-Bourel, A., 1965, A new inborn error of metabolism: Folic acid responsive megaloblastic anemia, ataxia, mental retardation and convulsions, Proceedings of the American Pediatric Society, Philadelphia, May 4–6.

    Google Scholar 

  • Lukens, L., and Flaks, J., 1963, Intermediates in purine nucleotide synthesis, in: Methods in Enzymology, Vol. 6 (S. P. Colowick and N. O. Kaplan, eds.), pp. 671–702, Academic Press, New York.

    Google Scholar 

  • Lynn, R., Rueter, M. E., and Guynn, R. W., 1977, Mammalian brain dihydrofolate reductase, J. Neurochem. 29:1147–1149.

    CAS  PubMed  Google Scholar 

  • MacKenzie, I. L., Donaldson, R. M., Jr., Trier, J. S., and Nathan, V. I., 1972, Ileal mucosa in familial selective vitamin B12 malabsorption, N. Engl. J. Med. 286:1021–1025.

    CAS  PubMed  Google Scholar 

  • Mahoney, M. J., and Rosenberg, L. E., 1975, Inborn errors of cobalamin metabolism, in: Cobalamin: Biochemistry and Pathophysiology (B. M. Babior, ed.), pp. 369–402, John Wiley and Sons, New York.

    Google Scholar 

  • Mahoney, M. J., Rosenberg, L. E., Mudd, S. H., and Uhlendorf, B. W., 1971, Defective metabolism of vitamin B12 in fibroblasts from children with methylmalonicacidemia, Biochem. Biophys. Res. Commun. 44:375–381.

    CAS  PubMed  Google Scholar 

  • Makulu, D. R., Smith, E. F., and Bertino, J. R., 1973, Lack of dihydrofolate reductase activity in brain tissue of mammalian species: Possible implications, J. Neurochem. 21:241–245.

    CAS  PubMed  Google Scholar 

  • Mangum, J. H., and Scrimgeour, K. G., 1962, Cofactor requirements and intermediate in methionine biosynthesis, Fed. Proc. Fed. Am. Soc. Exp. Biol. 21:242.

    Google Scholar 

  • Mangum, J. H., Murray, B. K., and North, J. A., 1969, Vitamin B12 dependent methionine biosynthesis in cultured mammalian cells, Biochemistry 8:3496–3499.

    CAS  PubMed  Google Scholar 

  • McBurney, M. W., and Whitmore, G. F., 1974a, Isolation and biochemical characterization of folate deficient mutants of Chinese hamster cells, Cell 2:173–182.

    CAS  PubMed  Google Scholar 

  • McBurney, M. W., and Whitmore, G. F., 1974b, Characterization of a Chinese hamster cell with a temperature-sensitive mutation in folate metabolism, Cell 2:183–188.

    CAS  PubMed  Google Scholar 

  • Meller, E., Rosengarten, H., Friedhoff, A. J., Stebbins, R. D., and Silber, R., 1975, 5-Methyltetrahydrofolic acid is not a methyl donor for biogenic amines: Enzymatic formation of formaldehyde, Science 187:171–173.

    CAS  PubMed  Google Scholar 

  • Mellman, I. S., Youngdahl-Turner, P., Willard, H. F., and Rosenberg, L. E., 1977, Intracellular binding of radioactive hydroxocobalamin to cobalamin-dependent apoenzymes in rat liver, Proc. Natl. Acad. Sci. U.S.A. 74:916–920.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Metz, J., Kelly, A., Swett, V. C., Waxman, S., and Herbert, V., 1968, Deranged DNA synthesis by bone marrow from vitamin B12-deficient humans, Br. J. Haematol. 14:575–592.

    CAS  PubMed  Google Scholar 

  • Milstien, S., Holtzman, N. A., O’Flynn, M. E., Thomas, G. H., Butler, I. J., and Kaufman, S., 1976, Hyperphenylalaninemia due to dihydropteridine reductase deficiency, J. Pediatr. 89:763–766.

    CAS  PubMed  Google Scholar 

  • Mudd, S. H., 1973, Biochemical mechanisms in methyl group transfer, in: Metabolic Conjugation and Metabolic Hydrolysis, Vol. 3 (W. H. Fishman, ed.), pp. 297–350, Academic Press, New York.

    Google Scholar 

  • Mudd, S. H., 1974, Homocystinuria and homocysteine metabolism: Selected aspects, in: Heritable Disorders of Amino Acid Metabolism (W. L. Nyhan, ed.), pp. 429–451, John Wiley and Sons, New York.

    Google Scholar 

  • Mudd, S. H., and Cantoni, G. L., 1964, Biological transmethylation, methyl-group neogenesis and other “one-carbon” metabolic reactions dependent upon tetrahydrofolic acid, in: Comprehensive Biochemistry (M. Florkin and E. H. Stotz, eds.), pp. 1–47, Elsevier, New York.

    Google Scholar 

  • Mudd, S. H., and Levy, H. L., 1978, Disorders of transsulfuration, in: The Metabolic Basis of Inherited Disease (J. B. Stanbury, J. B. Wyngaarden, and D. S. Fredrickson, eds.), pp. 458–503, McGraw-Hill, New York.

    Google Scholar 

  • Mudd, S. H., and Poole, J. R., 1975, Labile methyl balances for normal humans on various dietary regimens, Metabolism 24:721–735.

    CAS  PubMed  Google Scholar 

  • Mudd, S. H., Finkelstein, J. D., Irreverre, F., and Laster, L., 1965, Transsulfuration in mammals, microassays and tissue distributions of three enzymes of the pathway, J. Biol. Chem. 240:4382–4392.

    CAS  PubMed  Google Scholar 

  • Mudd, S. H., Levy, H. L., and Morrow, G., 1970a, Deranged B12 metabolism: Effects on sulfur amino acid metabolism, Biochem. Med. 4:193–214.

    CAS  PubMed  Google Scholar 

  • Mudd, S. H., Uhlendorf, B. W., Hinds, K. R., and Levy, H. L., 1970b, Deranged B12 metabolism: Studies of fibroblasts grown in tissue culture, Biochem. Med. 4:215–239.

    CAS  PubMed  Google Scholar 

  • Mudd, S. H., Uhlendorf, B. W., Freeman, J. M., Finkelstein, J. D., and Shih, V. E., 1972, Homocystinuria associated with decreased methylenetetrahydrofolate reductase activity, Biochem. Biophys. Res. Commun. 46:905–912.

    CAS  PubMed  Google Scholar 

  • Nakamura, H., and Littlefield, J. W., 1972, Purification, properties, and synthesis of dihydrofolate reductase from wild-type and methotrexate-resistant hamster cells, J. Biol. Chem. 247:179–187.

    CAS  PubMed  Google Scholar 

  • Nakano, Y., Fujioka, M., and Wada, H., 1968, Studies on serine hydroxymethylase isoenzymes from rat liver, Biochim. Biophys. Acta 159:19–26.

    CAS  PubMed  Google Scholar 

  • Narisawa, K., 1979, Brain damage in infantile type of 5,10-methylenetetrahydrofolate re-

    Google Scholar 

  • ductase deficiency, in: Folic Acid in Neurology, Psychiatry, and Internal Medicine (M. I. Botez, ed.), pp. 391–400, Raven Press, New York.

    Google Scholar 

  • Narisawa, K., Wada, Y., Saito, T., Suzuki, H., Kudo, M., Arakawa, T., Katsushima, N., and Tsuboi, R., 1977, Infantile type of homocystinuria with N 5,10-methylenetetrahy-drofolate reductase defect, Tohoku J. Exp. Med. 121:185–194.

    CAS  PubMed  Google Scholar 

  • Niederwieser, A., Giliberti, P., Matasovic, A., Pluznik, S., Steinmann, B., and Baerlocher, K., 1974, Folic acid non-dependent formiminoglutamic aciduria in two siblings, Clin. Chim. Acta 54:293–316.

    CAS  PubMed  Google Scholar 

  • Niethammer, D., and Huennekens, F. M., 1973, Transport of folic acid, 5-methyltetrahy-drofolic acid and methotrexate through the membrane of lymphocytes, in: Erythrocytes, Thrombocytes, Leukocytes (E. Gerloch, K. Moser, E. Deutsch, and W. Wilmanns, eds.), pp. 504–508, Georg Thieme, Stuttgart.

    Google Scholar 

  • Nixon, P. F., and Bertino, J. R., 1972a, Effective absorption and utilization of oral formyltetrahydrofolate in man, N. Engl. J. Med. 286:175–179.

    CAS  PubMed  Google Scholar 

  • Nixon, P. F., and Bertino, J. R., 1972b, Impaired utilization of serum folate in pernicious anemia: A study with radiolabeled 5-methyltetrahydrofolate, J. Clin. Invest. 51:1431–1439.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Nixon, P. F., Slutsky, G., Nahas, A., and Bertino, J. R., 1973, The turnover of folate coenzymes in murine lymphoma cells, J. Biol. Chem. 248:5932–5936.

    CAS  PubMed  Google Scholar 

  • Noronha, J. M., and Silverman, M., 1962, On folic acid, vitamin B12, methionine and formiminoglutamic acid metabolism, in: Vitamin B l2 und Intrinsic Factor, Vol. 2, Europäisches Symposion (H. C. Heinrich, ed.), pp. 728–736, Ferdinand Enke, Stuttgart.

    Google Scholar 

  • Nyhan, W. L., 1978, Nonketotic hyperglycinemia, in: The Metabolic Basis of Inherited Disease (J. B. Stanbury, J. B. Wyngaarden and D. S. Fredrickson, eds.), pp. 518–527, McGraw-Hill, New York.

    Google Scholar 

  • Ordonez, L. A., and Caraballo, F. F., 1975, Methylene reductase: Responsible for the in vitro formation of formaldehyde from 5-methyltetrahydrofolic acid, Psychopharmacol. Commun. 1:253–260.

    CAS  PubMed  Google Scholar 

  • Osborne-White, W. S., and Smith, R. M., 1973, Identification and measurement of folates in sheep liver, Biochem. J. 136:265–278.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Patterson, D., 1975, Biochemical genetics of Chinese hamster cell mutants with deviant purine metabolism: Biochemical analysis of eight mutants, Somatic Cell Genet. 1:91–110.

    CAS  PubMed  Google Scholar 

  • Paukert, J. L., Straus, L. D., and Rabinowitz, J. C., 1976, Formyl-methenyl-methylene-tetrahydrofolate synthetase-(combined): An ovine protein with multiple catalytic activities, J. Biol. Chem. 251:5104–5111.

    CAS  PubMed  Google Scholar 

  • Pearson, A. G. M., and Turner, A. J., 1975, Folate-dependent 1-carbon transfer to biogenic amines mediated by methylenetetrahydrofolate reductase, Nature (London) 258:173–174.

    CAS  Google Scholar 

  • Pegg, A. E., 1971, Studies on inhibitors of mammalian tRNA methylases, FEBS Lett. 16:13–16.

    CAS  PubMed  Google Scholar 

  • Perry, T. L., 1974, Homocystinuria, in: Heritable Disorders of Amino Acid Metabolism (W. L. Nyhan, ed.), pp. 395–428, John Wiley and Sons, New York.

    Google Scholar 

  • Perry, T. L., Applegarth, D. A., Evans, M. E., and Hansen, S., 1975, Metabolic studies of a family with massive formiminoglutamic aciduria, Pediatr. Res. 9:117–122.

    CAS  PubMed  Google Scholar 

  • Plaut, G. W. E., Betheil, J. J., and Lardy, H. A., 1950, The relationship of folic acid to formate metabolism in the rat, J. Biol. Chem. 184:795–805.

    CAS  PubMed  Google Scholar 

  • Pollin, W., Cardon, P. V., Jr., and Kety, S. S., 1961, Effects of amino acid feedings in schizophrenic patients treated with iproniazid, Science 133:104–105.

    CAS  PubMed  Google Scholar 

  • Pollock, R. J., and Kaufman, S., 1978, Dihydropteridine reductase may function in tetrahy-drofolate metabolism, J. Neurochem. 31:115–123.

    CAS  PubMed  Google Scholar 

  • Puck, T. T., 1972, The Mammalian Cell as a Microorganism, Holden-Day, San Francisco, 219 pp.

    Google Scholar 

  • Rosenberg, I. H., 1975, Folate absorption and malabsorption, N. Engl. J. Med. 293:1303–1308.

    CAS  PubMed  Google Scholar 

  • Rosenberg, I. H., and Godwin, H. A., 1971, The digestion and absorption of dietary folate, Gastroenterology 60:445–463.

    CAS  PubMed  Google Scholar 

  • Rosenberg, L. E., 1978, Disorders of propionate, methylmalonate, and cobalamin metabolism, in: The Metabolic Basis of Inherited Diseases (J. B. Stanbury, J. B. Wyngaarden, and D. S. Fredrickson, eds.), pp. 411–429, McGraw-Hill, New York.

    Google Scholar 

  • Rosenblatt, D. S., and Erbe, R. W., 1972, Methylene-tetrahydrofolate reductase in human cells from normals and from a family with reductase deficiency, Am. J. Hum. Genet. 24:65a.

    Google Scholar 

  • Rosenblatt, D. S., and Erbe, R. W., 1973, Reciprocal changes in the levels of functionally related folate enzymes during the culture cycle in human fibroblasts, Blochem. Biophys. Res. Commun. 54:1627–1633.

    CAS  Google Scholar 

  • Rosenblatt, D. S., and Erbe, R. W., 1977a, Methylenetetrahydrofolate reductase in cultured human cells. I. Growth and metabolic studies, Pediatr. Res. 11:1137–1141.

    CAS  PubMed  Google Scholar 

  • Rosenblatt, D. S., and Erbe, R. W. 1977b, Methylenetetrahydrofolate reductase in cultured human cells. II. Genetic and biochemical studies of methylenetetrahydrofolate reductase deficiency, Pediatr. Res. 11:1141–1143.

    CAS  PubMed  Google Scholar 

  • Rowe, P. B., 1971, Inborn errors of folic acid metabolism: Regulation of active derivatives of folic acid, Minn. Med. 54:391–396.

    CAS  PubMed  Google Scholar 

  • Rowe, P. B., 1978, Inherited disorders of folate metabolism, in: The Metabolic Basis of Inherited Disease (J. B. Stanbury, J. B. Wyngaarden, and D. S. Fredrickson, eds.), pp. 430–457, McGraw-Hill, New York.

    Google Scholar 

  • Rundles, R. W., and Brewer, S. S., Jr., 1958, Hematologic responses in pernicious anemia to orotic acid, Blood 13:99–115.

    CAS  PubMed  Google Scholar 

  • Santiago-Borrero, P. J., Santini, R., Jr., Perez-Santiago, E., and Maldonado, N., 1973, Congenital isolated defect of folic acid absorption, J. Pediatr. 82:450–455.

    CAS  PubMed  Google Scholar 

  • Schnell, M., and Ordóñez, L. A., 1977, Uptake and metabolism of 5-methyltetrahydrofolic acid by rat brain slices, J. Neurochem. 29:121–126.

    CAS  PubMed  Google Scholar 

  • Scott, C. R., Hakami, N., Teng, C. C., and Sagerson, R. N., 1972, Hereditary transco-balamin II deficiency: The role of transcobalamin II in vitamin B12-mediated reactions, J. Pediatr. 81:1106–1111.

    CAS  PubMed  Google Scholar 

  • Shih, V. E., Salam, M. Z., Mudd, S. H., Uhlendorf, B. W., and Adams, R. D., 1972, A new form of homocystinuria due to N 5,10-methylenetetrahydrofolate reductase deficiency, Pediatr. Res. 6:135.

    Google Scholar 

  • Shiman, R., Akino, M., and Kaufman, S., 1971, Solubilization and partial purification of tyrosine hydroxylase from bovine adrenal medulla, J. Biol. Chem. 246:1330–1340.

    CAS  PubMed  Google Scholar 

  • Shin, Y. S., Williams, M. A., and Stokstad, E. L. R., 1972, Identification of folic acid compounds in rat liver, Biochem. Biophys. Res. Commun. 47:35–43.

    CAS  PubMed  Google Scholar 

  • Shin, Y. S., Buehring, K. U., and Stokstad, E. L. R., 1974, Studies of folate compounds in nature: Folate compounds in rat kidney and red blood cells, Arch. Biochem. Biophys. 163:211–224.

    CAS  PubMed  Google Scholar 

  • Smith, R. M., and Osborne-White, W. S., 1973, Folic acid metabolism in vitamin B12-deficient sheep: Depletion of liver folates, Biochem. J. 136:279–293.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Synder, S. H., Banerjee, S. P., Yamamura, H. I., and Greenberg, D., 1974, Drugs, neurotransmitters, and schizophrenia, Science 184:1243–1253.

    Google Scholar 

  • Spector, R., 1977, Identification of folate binding macromolecule in rabbit choroid plexus, J. Biol. Chem. 252:3364–3370.

    CAS  PubMed  Google Scholar 

  • Spector, R., and Lorenzo, A. V., 1975a, Folate transport by the choroid plexus in vitro, Science 187:540–542.

    CAS  PubMed  Google Scholar 

  • Spector, R., and Lorenzo, A. V., 1975b, Folate transport in the central nervous system, Am. J. Physiol. 229:777–782.

    CAS  PubMed  Google Scholar 

  • Spector, R., Levy, R., and Abelson, H. T., 1977a, Identification of dihydrofolate reductase in rabbit brain, Biochem. Pharmacol. 26:1507–1511.

    CAS  PubMed  Google Scholar 

  • Spector, R., Levy, P., and Abelson, H. T., 1977b, The development and regional distribution of dihydrofolate reductase in rabbit brain, J. Neurochem. 29:919–921.

    CAS  PubMed  Google Scholar 

  • Spector, R., Fosburg, M., Levy, P., and Abelson, H. T., 1978, Tetrahydrobiopterin synthesis by rabbit brain dihydrofolate reductase, J. Neurochem. 30:899–901.

    CAS  PubMed  Google Scholar 

  • Spronk, A. M., 1974, Tetrahydrofolate polyglutamate synthesis in rat liver, Fed. Proc. Fed. Am. Soc. Exp. Biol. 32:471.

    Google Scholar 

  • Stebbins, R. D., Meller, E., Rosengarten, H., Friedhoff, A., and Silber, R., 1976, Identification of N 5, N 10-methylene tetrahydrofolate reductase as the enzyme involved in the 5-methyl tetrahydrofolate-dependent formation of a β-carboline derivative of 5-hydroxytryptamine in human platelets, Arch. Biochem. Biophys. 173:673–679.

    CAS  PubMed  Google Scholar 

  • Stekol, J. A., and Szaran, J., 1962, Pathological effects of excessive methionine in the diet of growing rats, J. Nutr. 77:81–90.

    CAS  PubMed  Google Scholar 

  • Stokstad, E. L. R., 1977, Regulation of folate metabolism by vitamin B12, in: Folic Acid: Biochemistry and Physiology in Relation to the Human Nutrition Requirement, pp. 122–135, National Academy of Sciences, Washington, D.C.

    Google Scholar 

  • Szybalski, W., Szybalska, E. H., and Ragni, G., 1962, Genetic studies with human cell lines, Natl. Cancer Inst. Monogr. 7:75–88.

    Google Scholar 

  • Tabor, H., and Wyngarden, L., 1959, The enzymatic formation of formiminotetrahydrofolic acid, 5,10-methylenetetrahydrofolic acid, and 10-formyltetrahydrofolic acid in the metabolism of formiminoglutamic acid, J.. Biol. Chem. 234:1830–1846.

    CAS  PubMed  Google Scholar 

  • Tan, L. U. L., Drury, E. J., and MacKenzie, R. E., 1977, Methylenetetrahydrofolate dehydrogenase-methenyltetrahydrofolate cyclohydrolase-formyltetrahydrofolate synthetase: A multifunctional protein from porcine liver, J. Biol. Chem. 252:1117–1122.

    CAS  PubMed  Google Scholar 

  • Tauro, G. P., Danks, D. M., Rowe, P. B., Van der Weyden, M. B., Schwarz, M. A., Collins, V. L., and Neal, B. W., 1976, Dihydrofolate reductase deficiency causing megaloblastic anemia in two families, N. Engl. J. Med. 294:466–470.

    CAS  PubMed  Google Scholar 

  • Taylor, R. T., and Hanna, M. L., 1975a, Folate-dependent enzymes in cultured Chinese hamster ovary cells: Induction of 5-methyltetrahydrofolate homocysteine cobalamin methyltransferase by folate and methionine, Arch. Biochem. Biophys. 171:507–520.

    CAS  PubMed  Google Scholar 

  • Taylor, R. T., and Hanna, M. L., 1975b, 5-Methyltetrahydrofolate aromatic alkylamine N-methyltransferase: An artefact of 5,10-methylenetetrahydrofolate reductase activity, Life Sci. 17:111–120.

    CAS  PubMed  Google Scholar 

  • Taylor, R. T., and Hanna, M. L., 1977, Folate-dependent enzymes in cultured Chinese hamster cells: Folylpolyglutamate synthetase and its absence in mutants auxotrophic for glycine + adenosine + thymidine, Arch. Biochem. Biophys. 181:331–344.

    CAS  PubMed  Google Scholar 

  • Thenen, S. W., and Stokstad, E. L. R., 1973, Effect of methionine on specific folate coenzyme pools in vitamin B12 deficient and supplemented rats, J. Nutr. 103:363–370.

    CAS  PubMed  Google Scholar 

  • Tisman, G., and Herbert, V., 1973, B12 dependence of cell uptake of serum: An explanation for high serum folate and cell folate depletion in B12 deficiency. Blood 41:465–469.

    CAS  PubMed  Google Scholar 

  • Van Der Weyden, M. B., Cooper, M., and Firkin, B. G., 1973, Defective DNA synthesis in human megaloblastic bone marrow: Effects of hydroxy-B12, 5′-deoxyadenosyl-B12 and methyl-B12, Blood 41:299–308.

    PubMed  Google Scholar 

  • Walters, T., 1967, Congenital megaloblastic anemia responsive to N 5-formyltetrahydro-folic acid administration, J. Pediatr. 70:686–687.

    Google Scholar 

  • Wang, F. K., Koch, H., and Stokstad, E. L. R., 1967, Folate coenzyme pattern, folate linked enzymes and methionine biosynthesis in rat liver mitochondria, Biochem. Z. 346:458–466.

    CAS  PubMed  Google Scholar 

  • Waters, A. H., and Mollin, D. L., 1963, Observations on the metabolism of folic acid in pernicious anaemia, Br. J. Haematol. 9:319–327.

    CAS  PubMed  Google Scholar 

  • Waxman, S., 1975, Annotation: Folate binding proteins, Br. J. Haematol. 29:23–29.

    CAS  PubMed  Google Scholar 

  • Waxman, S., and Schreiber, C., 1974, The role of folic acid binding proteins (FABP) in the cellular uptake of folates, Proc. Soc. Exp. Biol. Med. 147:760–764.

    CAS  PubMed  Google Scholar 

  • Whitehead, V. M., 1971, Study of the folate polyglutamates in liver from animals and man, Blood 38:809.

    Google Scholar 

  • Whitehead, V. M., Pratt, R., Viallet, A., and Cooper, B. A., 1972, Intestinal conversion of folinic acid to 5-methyltetrahydrofolate in man, Br. J. Haematol. 22:63–72.

    CAS  PubMed  Google Scholar 

  • Wilkinson, D. S., Solomonson, L. P., and Cory, J. G., 1977, Increased thymidylate synthetase activity in 5-fluorodeoxyuridine-resistant Novikoff hepatoma cells, Proc. Soc. Exp. Biol. Med. 154:368–371.

    CAS  PubMed  Google Scholar 

  • Willard, H. F., Mellman, I. S., and Rosenberg, L. E., 1978, Genetic complementation among inherited deficiencies of methylmalonyl-CoA mutase activity: Evidence for a new class of human cobalamin mutant, Am. J. Hum. Genet. 30:1–13.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wong, P. W. K., Justice, P., Hruby, M., Weiss, E. B., and Diamond, E., 1977a, Folic acid nonresponsive homocystinuria due to methylenetetrahydrofolate reductase deficiency, Pediatrics 59:749–756.

    CAS  PubMed  Google Scholar 

  • Wong, P. W. K., Justice, P., and Berlow, S., 1971b, Detection of homozygotes and heterozygotes with methylenetetrahydrofolate reductase deficiency, J. Lab. Clin. Med. 90:283–288.

    Google Scholar 

  • Wright, B. E., 1955, A new cofactor in the conversion of serine to glycine, Biochim. Biophys. Acta 16:165–166.

    CAS  PubMed  Google Scholar 

  • Youngdahl-Turner, P., Rosenberg, L. E., and Allen, R. H., 1978, Binding and uptake of transcobalamin 11 by human fibroblasts, J. Clin. Invest. 61:133–141.

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zamierowski, M. M., and Wagner, C., 1977, Identification of folate binding proteins in rat liver, J. Biol. Chem. 252:933–938.

    CAS  PubMed  Google Scholar 

  • Zappia, V., Zydek-Cwick, C. R., and Schlenk, F., 1969, The specificity of 5-adenosylme-thionine derivatives in methyl transfer reactions, J. Biol Chem. 244:4499–4509.

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Genetics Unit, Children’s Service, Massachusetts General Hospital, Boston, Massachusetts, 02114, USA

    Richard W. Erbe

  2. Department of Pediatrics and Center for Human Genetics, Harvard Medical School, Boston, Massachusetts, 02114, USA

    Richard W. Erbe

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  1. Richard W. Erbe
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Editors and Affiliations

  1. University of Pennsylvania, Philadelphia, USA

    Harry Harris (Harnwell Professor of Human Genetics) (Harnwell Professor of Human Genetics)

  2. Mount Sinai School of Medicine, The City University of New York, USA

    Kurt Hirschhorn (Arthur J. and Nellie Z. Cohen Professor of Genetics and Pediatrics) (Arthur J. and Nellie Z. Cohen Professor of Genetics and Pediatrics)

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© 1979 Plenum Press, New York

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Erbe, R.W. (1979). Genetic Aspects of Folate Metabolism. In: Harris, H., Hirschhorn, K. (eds) Advances in Human Genetics 9. Advances in Human Genetics, vol 9. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-8276-2_5

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  • DOI: https://doi.org/10.1007/978-1-4615-8276-2_5

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