Folates and folic acid: From fundamental research toward sustainable health

Critical Reviews in Plant Sciences

Volumn 29, Issue 1, 2010, Pages 14-35

  Blancquaert, Dieter ^a   Storozhenko, Sergei ^a   Loizeau, Karen ^a   de Steur, Hans ^a   de Brouwer, Veerle ^a   Viaene, Jacques ^a   Ravanel, Stéphane ^b   Rébeillé, Fabrice ^b   Lambert, Willy ^a   van der Straeten, Dominique ^a  

^a GHENT UNIVERSITY   (Belgium)

^b Laboratoire de Physiologie Cellulaire Vegetale Grenoble   (France)

Author keywords

Agroeconomics; Biofortification; Metabolic engineering; Natural variation; Neural tube defects

Indexed keywords

ANIMALIA; BACTERIA (MICROORGANISMS);

EID: 77449107537     PISSN: 07352689     EISSN: 15497836     Source Type: Journal    
DOI: 10.1080/07352680903436283     Document Type: Article

References (212)

1. Akhtar, T. A., McQuinn, R. P., Naponelli, V., Gregory, J. F. III, Giovannoni, J. J., and Hanson, A. D. 2008. Tomato gamma-glutamylhydrolases: expression, characterization, and evidence for heterodimer formation. Plant Physiol. 148: 775-785.
2. Allfrey, V. G., Faulkner, R., and Mirsky, A.E. 1964. Acetylation and methylation of histones and their possible role in the regulation of RNA synthesis. Proc. Natl. Acad. Sci.USA 51: 786-794.
3. Appling, D. R. 1991. Compartmentation of folate-mediated one-carbon metabolism in eukaryotes. FASEB J. 5: 2645-2651.
4. Bailey, L. B. 2004. Folate and Vitamin B12 recommended intakes and status in the United States. Nutr. Rev. 62: S14-S20.
5. Bailly, C. 2004. Active oxygen species and antioxidants in seed biology. Seed Sci. Res. 14: 93-107.
6. Basset, G., Quinlivan, E. P., Ziemak, M. J., Diaz de la Garza, R., Fischer, M., Schiffmann, S., Bacher, A., Gregory, J. F. III, and Hanson, A. D. 2002. Folate synthesis in plants: the first step of the pterin branch is mediated by a unique bimodular GTP cyclohydrolase I. Proc. Natl. Acad. Sci. USA 99: 12489-12494.
7. Basset, G. J., Quinlivan, E. P., Ravanel, S., Rébeillé, F., Nichols, B. P., Shinozaki, K., Seki, M., Adams-Philips, L. C., Giovannoni, J. J., Gregory, J. F. III, and Hanson, A. D. 2004a. Folate synthesis in plants: the p-aminobenzoate branch is initiated by a bifunctional PabA-PabB protein that is targeted to plastids. Proc. Natl. Acad. Sci. USA 101: 1496-1501.
8. Basset, G. J. C., Ravanel, S., Quinlivan, E. P., White, R., Giovannoni, J. J., Rébeillé, F., Nichols, B. P., Shinozaki, K., Seki, M., Gregory, J. F. III, and Hanson, A. D. 2004b. Folate synthesis in plants: the last step of the p-aminobenzoate branch is catalyzed by a plastidial aminodeoxychorismate lyase. Plant J. 40: 453-461.
9. Basset, G. J. C., Quinlivan, E. P., Gregory, J. F. III, and Hanson, A. D. 2005. Folate synthesis and metabolism in plants and prospects for biofortification. Crop Sci. 45: 449-453.
10. Bedhomme, M., Hoffmann, M., McCarthy, E. A., Gambonnet, B., Moran, R. G., Rébeillé, F., and Ravanel, S. 2005. Folate metabolism in plants: an Arabidop-sis homolog of the mammalian mitochondrial folate transporter mediates folate import into chloroplasts. J. Biol. Chem. 280: 34823-34831.
11. Bekaert, S., Storozhenko, S., Mehrsahi, P., Bennet, M. J., Lambert, W., Gregory, J. F. III, Schubert, K., Hugenholtz, J., Van Der Straeten, D., and Hanson, A. D. 2008. Folate biofortification in food plants. Trends Plant Sci. 13, 28-34.
12. Bello, A. R., Nare, B., Freedman, D., Hardy, L., and Beverley, S. M. 1994. PTR1: a reductase mediating salvage of oxidized pteridines and methotrexate resistance in the protozoan parasite Leishmania major. Proc. Natl. Acad. Sci. USA 91: 11442-11446.
13. Berry, R., Li, Z., Erickson, D., Li, S., Moore, C., Wang, H., Mulinare, J., Zhao, P., Wong, L.-Y., Gindler, J., Hong, S.-X., and Correa, A. 1999. Prevention of neural-tube defects with folic acid in China. N Engl J Med. 341: 1485-1491.
14. Berry, R. J., and Li, Z. 2002. Folic acid alone prevents neural tube defects: Evidence from the China study. [Letter]. Epidemiology 13: 114-116.
15. Besson, V., Rébeillé, F., Neuburger, M., Douce, R., and Cossins, E. A. 1993. Effects of tetrahydrofolate polyglutamates on the kinetic parameter of serine hydroxymethyltransferase and glycine decarboxylase from pea leaf mitochondria. Biochem. J. 292: 425-430.
16. Bewley, J. D. 1997. Seed germination and dormancy. Plant Cell 9: 1055-1066.
17. Blackley, R. L. 1969. The biochemistry of folic acid and related pteridines. In: Frontiers of Biology, Vol. 13. Neuberger, A. and Tatum, E. L., Eds., North Holland, Amsterdam and London.
18. Block, M. A., Tewari, A. K., Albrieux, C., Marechal, E., and Joyard, J. 2002. The plant S-adenosyl-L-methionine: Mg-protoporphyrin IX methyl-transferase is located in both envelope and thylakoid chloroplast membranes. Eur. J. Biochem. 269: 240-248.
19. Blomhoff, R. 2005. Dietary antioxidants and cardiovascular disease. Curr. Opin. Lipidol. 16: 47-54.
20. Bognar, A. L., Osborne, C., Shane, B., Singer, S. C., and Ferone, R. 1985. Folylpoly-gamma-glutamate synthetase-dihydrofolate synthetase-cloning and high expression of the Escherichia coli FolC gene and purification and properties of the gene product. J. Biol. Chem. 260: 5625-5630.
21. Bonaa, K. H., Njolstad, I., Ueland, P. M., Schirmer, H., Tverdal, A., Steigen, T., Wang, H., Nordrehaug, J. E., Arnesen, E., and Rasmussen, K. 2006. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N. Eng, J. Med. 354: 1578-1588.
22. Bonti-Ankomah, S., and Yiridoe, E. 2006. Organic and Conventional Food: A Literature Review of the Economics of Consumer Perceptions and Preferences. Organic Agriculture Centre of Canada, Canada.
23. Bozzo, G. G., Basset, G. J. C., Naponelli, V., Noiriel, A., Gregory, J. F. III, and Hanson, A. D. 2008. Characterization of the folate salvage enzyme p-aminobenzoylglutamate hydrolase in plants. Phytochemistry. 69: 29-37.
24. Brown, G. M., Weisman, R. A., and Molnar, D. A. 1961. The biosynthesis of folic acid. 1. Substrate and cofactor requirements for enzymatic synthesis by cell-free extracts of Escherichia coli. J. Biol. Chem. 236: 2534-2543.
25. Cella, R., and Parisi, B. 1993. Dihydrofolate reductase and thymidylate synthase in plants - an open problem. Physiol. Plant. 88: 509-521.
26. Chen, L., Chan, S. Y., and Cossins, E. A. 1997. Distribution of folate deriva-tives and enzymes for synthesis of 10-formyltetrahydrofolate in cytosolic and mitochondrial fractions of pea leaves. Plant. Physiol. 115: 299-309.
27. Chen, L. L., Marmey, P., Taylor, N. J., Brizard, J. P., Espinoza, C., D'Cruz, P., Huet, H., Zhang, S. P., de Kochko, A., Beachy, R. N., and Fauquet, C. M. 1998. Expression and inheritance of multiple transgenes in rice plants. Nat. Biotechnol. 16: 1060-1064.
28. Cherian, A., Seena, S., Bullock, R. K., and Antony, A. C. 2005. Incidence of neural tube defects in the least-developed area of India: a population-based study. Lancet 366: 930-931.
29. Choi, S. W., and Friso, S. 2005. Interactions between folate and aging for carcinogenesis. Clin. Chem. Lab. Med. 43: 1151-1157.
30. Choumenkovitch, S. F., Selhub, J., Wilson, P. W. F., Rader, J. I., Rosenberg, I. H., and Jacques, P. F. 2002. Folic acid intake from fortification in United States exceeds predictions. J. Nutr. 132: 2792-2798.
31. CNGOIC 2009. Food Grains Weekly Report. National Grain and Oils Informa-tion Center, Beijing.
32. Cole, B. F., Baron, J. A., Sandler, R. S., Haile, R. W., Ahnen, D. J., Bresalier, R. S., Mckeown-Eyssen, G., Summers, R. W., Rothstein, R., Burke, C. A., Snover, D. C., Church, T. R., and Byers, T. 2005.A randomised trial of folic acid to prevent colorectal adenomas. Proc. Amer. Assoc. Cancer Res. 46: 4399.
33. Cook, R. J. 2001. Disruption of histidine catabolism in NEUT2 mice. Arch. Biochem. Biophys. 392: 226-232.
34. Cossins, E. A. 2000. The fascinating world of folateandone-carbonmetabolism. Can. J. Bot. 78: 691-708.
35. Costa-Font, M., Gil, J., and Traill, W. 2008. Consumer acceptance, valuation of and attitudes towards genetically modified food: Review and implications for food policy. Food Policy. 33: 99-111.
36. Crosti, P., Malerban,M., and Blanchetti, R. 1993. Growth-dependent changes of folate metabolism and biosynthesis in cultured Daucus carota cells. Plant Sci. 88: 97-106.
37. Dallas, W. S., Gowen, J. E., Ray, P. H., Cox, M. J., and Dev, I. K. 1992. Cloning, sequencing, and enhanced expression of the dihydropteroate synthase gene of Escherichia coli MC4100. J. Bacteriol. 174: 5961-5970.
38. Daly, S., Mills, J., Molloy, A., Conley, M., Lee, Y., Kirke, P., Weir, D., and Scott, J. 1997. Minimum effective dose of folic acid for food fortification to prevent neural-tube defects. Lancet 350: 1666-1669.
39. Daubner, S. C., and Matthews, R. G. 1982. Purification and properties of methylenetetrahydrofolate reductase from pig liver. J. Biol. Chem. 257: 140-145.
40. DeSouza, L., Shen, Y., and Bognar, A. L. 2000. Disruption of cytoplasmic and mitochondrial folylpolyglutamate synthetase activity in Saccharomyces cerevisiae. Arch. Biochem. Biophys. 376: 299-312.
41. De Steur, H., Gellynck, X., Storozhenko, S., Liqun, G., Lambert, W., Van Der Straeten, D., and Viaene, J. 2009. Willingness to accept and purchase genetically modified rice with high folate content in Shanxi province, China. Appetite, doi: 10.1016/j.appet.2009.09.017.
42. De Wals, P., Tairou, F., Van Allen, M. I., Uh, S., Lowry, R. B., Sibbald, B., Evans, J. A., Van den Hof, M. C., Zimmer, P., Crowley, M., Fernandez, B., Lee, N. S., and Niyonsenga, T. 2007. Reduction in neural-tube defects after folic acid fortification in Canada. New Engl. J. Med. 357: 135-142.
43. Diaz de la Garza, R., Quinlivan, E. P., Klaus, S. M., Basset, G. J., Gregory, J. F. III, and Hanson, A. D. 2004. Folate biofortification in tomatoes by engineering the pteridines branch of folate synthesis. Proc. Natl. Acad. Sci. USA 101: 13720-13725.
44. Diaz de la Garza, R. I., Gregory, J. F. III, and Hanson, A. D. 2007. Folate biofortification of tomato fruit. Proc. Natl. Acad. Sci. USA 104: 4218-4222.
45. Douce, R., Bourguignon, J., Neuburger, M., and Rébeillé, F. 2001. The glycine decarboxylase system: a fascinating complex. Trends Plant Sci. 6: 167-176.
46. Eudes, A., Bozzo, G. G., Waller, J. C., Naponelli, V., Lim, E. K., Bowles, D. J., Gregory, J. F. III, and Hanson, A. D. 2008. Metabolism of the folate precursor p-aminobenzoate in plants. Glucose ester formation and vacuolar storage. J. Biol. Chem. 283: 15451-15459.
47. Fan, C. L., and Brown, G. M. 1976. Partial purification and properties of guanosine triphosphate cyclohydrolase from Drosophila melanogaster. Biochem. Gen. 14: 259-270.
48. Ferone, R. 1973. The enzymatic synthesis of dihydropteroate and dihydrofolate by Plasmodium berghei. J. Protozool. 20: 459-464.
49. Finglas, P. M., de Meer, K., Molloy, A., Verhoef, P., Pietrzik, K., Powers, H. J., Van Der Straeten, D., Jagerstad, M., Varela-Moreiras, G., van Vliet, T., Havenaar, R., and Buttriss, J. 2006. Research goals for folate and related B vitamin in Europe. Eur. J. Clin. Nutr. 60: 287-294.
50. Food and Drug Administration 1996. Food standards: amendments of standards of identity for enriched grain products to require addition of folic acid. Final Rule. 21 CFR Parts 136, 137, 139: 8781-8807.
51. Forrest, H. S., and Van Baalen, C. 1970. Microbiology of unconjugated pteridines. Annu. Rev. Microbiol. 34: 91-108.
52. Fowler, B. 2001. The folate cycle and disease in humans. Kidney Int. 78: S221-S229.
53. Foyer, C. H., and Noctor, G. 2005. Oxidant and antioxidant signaling in plants: a re-evaluation of the concept of oxidative stress in a physiological context. Plant Cell. Environ. 28: 1056-1071.
54. Freemantle, S. J., Taylor, S. M., Krystal, G., and Moran, R. G. 1995. Upstream organization of and multiple transcripts from the human folylpoly-gamma-glutamate synthase gene. J. Biol. Chem. 270: 9579-9584.
55. Gambonnet, B., Jabrin, S., Ravanel, S., Karan, M., Douce, R., and Rébeillé, F. 2001. Folate distribution during higher plant development. J. Sci. Food Agric. 81: 835-841.
56. Gao, Y. S., Alvarez, C., Nelson, D. S., and Sztul, E. 1998. Molecular cloning, characterization, and dynamics of rat formiminotransferase cyclodeaminase, a Golgi-associated 58 kDa protein. J. Biol. Chem. 273: 33825-33834.
57. Gao, Y. L., Guo, F., Gokavi, S., Chow, A., Sheng, Q. H., and Guo, M. R. 2008. Quantification of water-soluble vitamins in milk-based infant formulae using biosensor-based assays. Food Chem. 110: 769-776.
58. Garcia, A. A., Day, A. G., Zanibbi, K., and Zunzunegui, M. V. 2008. Long-term effects of folic acid fortification and B-vitamin supplementation on total folate, homocysteine, methylmalonic acid and cobalamin in older adults. Can. J. Public Health 99: 428-433.
59. Geisel, J. 2003. Folic acid and neural tube defects in pregnancy - A review. J. Perinat. Neonatal Nurs. 17: 268-279.
60. Goyer, A., Illarionova, V., Roje, S., Fischer, M., Bacher, A., and Hanson, A. D. 2004. Folate biosynthesis in higher plants. cDNA cloning, heterologous expression,and characterization of dihydroneopterin aldolases. Plant Physiol. 135: 103-111.
61. Goyer, A., Collakova, E., Diaz de le Garza, R., Quinlivan, E. P., Williamson, J., Gregory, J. F. III, Shachar-Hill, Y., and Hanson, A. D. 2005. 5-Formyltetrahydrofolate is an inhibitory but well tolerated metabolite in Ara-bidopsis leaves. J. Biol. Chem. 280: 26137-26142.
62. Green, J. M., Merkel, W. K., and Nichols, B. P. 1992. Characterization and sequence of Escherichia coli PabC,the gene encoding aminodeoxychorismate lyase, a pyridoxal phosphate-containing enzyme. J. Bacteriol. 174: 5317-5323.
63. Green, N. S. 2002. Folic acid supplementation and prevention of birth defects. J. Nutr. 132: 2356S-2360S.
64. Gregory, J. F. III 1989. Chemical and nutritional aspects of folate research: an-alytical procedures, methods of folate synthesis, stability, and bioavailability of dietary folates. Adv. Food. Nutr. Res. 33: 1-101.
65. Gregory, J. F. 1995. The bioavailability of folate. In: Folate in Health and Disease. pp.195-235. Bailey, B. L., Ed., Marcel Dekker, New York.
66. Gregory, J. F. 1997. The bioavailability of vitamin B-6. Eur. J. Clin. Nutr. 51: S43-S48.
67. Gregory, J. F. III and Quinlivan, E. P. 2002. In vivo kinetics of folate metabolism. Annu. Rev. Nutr. 22: 199-200.
68. Gu, X., Lin, L., Zheng, X., Zhang, T., Song, X., Wang, J., Li, X., Li, P., Chen, P., Wu, J., Wu, L., and Liu, J. 2007. High prevalence of NTDs in Shanxi Province: A combined epidemiological approach. Birth Defects Res. A. Clin. Mol. Teratol. 79: 702-707.
69. Guldener, U., Koehler, G. J., Haussmann, C., Bacher, A., Kricke, J., Becher, D., and Hegemann, J. H. 2004. Characterization of the Saccharomyces cerevisiae Fol 1 protein: Starvation for C1 carrier induces pseudohyphal growth. Mol. Biol. Cell 15: 3811-3828.
70. 5-methyltetrahydrofolate in combined folate and B12 deficiency: Evidence in support of the "folate trap" hypothesis. Digest. Dis. Sci. 18: 142-146.
71. st century plant biotechnology. Plant Biotechnol. J. 3: 141-155.
72. Hanson, A. D., and Roje, S. 2001. One-carbon metabolism in higher plants. Annu. Rev. Plant Physiol. Plant Mol. Biol. 52: 119-137.
73. Hanson, A. D., and Gregory, J. F. 2002. Synthesis and turnover of folates in plants. Curr. Opin. Plant Biol. 5: 244-249.
74. Hare, P. D., and Chua, N. H. 2002. Excision of selectable marker genes from transgenic plants. Nat. Biotechnol. 20: 575-580.
75. Hennig, D., Scales, S. J., Moreau, A., Murley, L. L., De Mey, J., and Kreis, T. E. 1998. A formiminotransferase cyclodeaminase isoform is localized to the Golgi complex and can mediate interaction of trans-Golgi netwotk-derived vesicles with microtubules. J. Biol. Chem. 273: 19602-19611.
76. Hillcoat, B. L., Nixon, P. F., and Blakley, R. L. 1967. Effects of substrate decomposition on the spectrophotometric assay of dihydrofolate reductase. Anal. Biochem. 21: 178-189.
77. Ho, P., Vermeer, E., and Zhao, J. 2006. Biotechnology and food safety in China: consumer's acceptance or resistance? Dev. Change. 37: 227-254.
78. Hohn, B., Levy, A. A., and Puchta, H. 2001. Elimination of selectin markers from transgenic plants. Curr. Opin. Biotechnol. 12: 139-143.
79. Holland, B., Undwin, I. D., and Buss, D. H. 1996. Vegetables, Herbs and Spices. Fruit and Nuts. Fifth supplement to McCance and Widdowson's 'The Composition of Foods'. Cambridge the Royal Society of Chemistry and Ministry of Agriculture Fisheries and Food, Laboratory of the Government Chemist.
80. Hossain, T., Rosenberg, I., Selhub, J., Kishore, G., Beachy, R., and Schubert, K. 2004. Enhancement of folate in plants through metabolic engineering. Proc. Natl. Acad. Sci. USA 101: 5158-5163.
81. Hrazdina, G., and Jensen, R. A. 1992. Spatial organization of enzymes in plant metabolic pathways. Annu. Rev. Plant Physiol. Plant Mol. Biol. 43: 241-267.
82. Huang, J., Qiu, H., Bai, J., and Pray, C. 2006. Awareness, acceptance of and willingness to buy genetically modified foods in Urban China. Appetite. 46: 144-151.
83. Hubner, R. A., Houlston, R. D., and Muir, K. R. 2007. Should folic acid fortification be mandatory? No. B.M.J. 334: 1253.
84. Hussein, M. J., Green, J. M., and Nichols, B. P. 1998. Characterization of mu-tations that allow p-aminobenzoyl-polyglutamate utilization by Escherichia coli. J. Bacteriol. 180: 6260-6268.
85. Hutchinson, M. L., Jones, M. D., and Nixon, P. F. 2000. Stability of labile folate is enhanced by binding to milk folate binding protein. Aust. J. Dairy Technol. 55: 98.
86. Imeson, H. C., Zheng, L., and Cossins, E. A. 1990. Folylpolyglutamate derivates of Pisum sativum L. Determination of polyglutamate chain lengths by high-performance liquid chromatography following conversion to p-aminobenzoylpolyglutamates. Plant Cell Physiol. 31: 223-231.
87. Jabrin, S., Ravanel, S., Gambonnet, B., Douce, R., and Rébeillé, F. 2003. One-carbon metabolism in plants. Regulation of tetrahydrofolate synthesis during germination and seedling development. Plant Physiol. 131: 1431-1439.
88. Jacques, P. F., Selhub, J., Bostom, A. G., Wilson, P. W., and Rosenberg, I. H. 1999. The effect of folic acid fortification on plasma folate and total homocysteine concentrations. N. Engl. J. Med. 340:1449-1454.
89. Jain, A. K., and Nessler, C. L. 2000. Metabolic engineering of an alternative pathway for ascorbic acid biosynthesis in plants. Mol. Breed. 6: 73-78.
90. Johnson,J.L.,and Rajagopalan,K.V. 1985. Pterins in other metabolic pathways. In: Folates and Pterins, Vol. 2. pp. 383-399. Blackley, R. L., and Benkovic, S., Eds., J. Wiley (Interscience), New York.
91. Jones, M. L., and Nixon, P. F. 2002. Tetrahydrofolate are greatly stabilized by binding to bovine milk folate-binding protein. J. Nutr. 132: 2690-2694.
92. Kaufman, S., and Kaufman, E. E. 1985. Tyrosine hydroxylase. In: Folates and Pterins, Vol. 2. pp. 251-352. Blackley, R. L. and Benkovic, S., Eds., J. Wiley (Interscience), New York.
93. Klaus, S. M., Wegkamp, A., Sybesma, W., Hugenholtz, J., Gregory, J. F. III, and Hanson, A. D. 2005a. A nudix enzyme removes pyrophosphate from dihydroneopterin triphosphate in the folate synthesis pathway of bacteria and plants. J. Biol. Chem. 280: 5274-5280.
94. Klaus, S. M. J., Kunji, E. R. S., Bozzo, G. G., Noiriel, A., Diaz de la Garza, R., Basset, G. J. C., Ravanel, S., Rébeillé, F., Gregory, J. F. III, and Hanson, A. D. 2005b. Higher plant plastids and cyanobacteria have folate carriers related to those of Trypanosomatids. J. Biol. Chem. 280: 38457-38463.
95. Kobayashi, K., Forrest, H. S., and el-Emary, M. 1967. Isolation of 6-hydroxymethyllumazine(phosphodoxin?)andtwootherlumazinederivatives from spinach, and their synthesis. Arch. Biochem. Biophys. 121: 220-223.
96. Kohashi, M., Itadani, T., and Iwai, K. 1980a. Purification and characterization of guanosine triphosphate cyclohydrolase I from Serratia indica. Agric. Biol. Chem. 44: 271-278.
97. Kohashi, M. 1980b. Isolation of six unconjugated pteridines from soybean (Glycine max L. Tsurunoko) seeds. J. Biochem. (Tokyo) 91: 1581-1586.
98. Kohashi, M., Tomita, K., and Iwai, K. 1980c. Analysis of unconjugated pterins in food resources and human urine. Agric. Biol. Chem. 44: 2089-2094.
99. Kouzarides, T. 2002. Histone methylation in transcriptional control. Curr. Opin. Genet. Dev. 12: 198-209.
100. Kuhn, D. M., and Lovenberg, W. 1985. Tryptophan hydroxylase. In: Folates and Pterins, Vol. 2. pp. 115-154. Blackley, R. L. and Benkovic, S., Eds., J. Wiley (Interscience), New York.
101. Lewis, S. J., Harbord, R. M., Harris, R., and Smith, G. D. 2006. Meta-analyses of observational and genetic association studies of folate intakes or levels and breast cancer risk. J. Natl. Cancer Inst. 98:1607-1622.
102. Li, Q., Curtis, K., McCluskey, J., and Wahl, T. 2002. Consumer attitudes toward genetically modified foods in Beijing, China. AgBioForum. 5: 145-152.
103. Li, Z. W., Ren, A. G., Zhang, L., Guo, Z. Y., and Li, Z. 2006a. A population-based case-control study of risk factors for neural tube defects in four high-prevalence areas of Shanxi province, China. Paediatr. Perinat. Epidemiol. 20: 43-53.
104. Li, Z. W., Ren, A. G., Zhang, L., Ye, R. W., Li, S., Zheng, J. C., Hong, S. X., Wang, T. M., and Li, Z. 2006b. Extremely high prevalence of neural tube defects in a 4-county area in Shanxi Province, China. Birth Defects Res., Part A 76: 237-240.
105. Li, Z., Ren, A., Zhang, L., Liu, J., and Li, Z. 2007. Periconceptional use of folic acid in Shanxi Province of northern China. Public Health Nutr. 10: 471-476.
106. Lin, M., and Young, C. M. 2000. Biosynthesis of folates by Streptococcus thermophilus and Lactobacillus delbrueckii ssp. bulgaricus. J. Food Drug Anal. 8: 195-199.
107. Lin, S., Rogiers, S., and Cossins, E. A. 1993. Gamma-glutamyl hydrolase from pea cotyledons. Phytochemistry. 32: 1109-1117.
108. ′-D-2-deoxy-2-aminoglucopyranoside) isolated from the thermophilic archae-bacterium Sulfolobus solfataricus. J. Bacteriol. 170: 1396-1398.
109. Loizeau, K., Gambonnet, B., Zhang, G. F., Curien, G., Jabrin, S., Van Der Straeten, D., Lambert, W. E., Rébeillé, F., and Ravanel, S. 2007. Regulation of one-carbon metabolism in Arabidopsis: the N-terminal regulatory domain of cystathionine gamma-synthase is cleaved in response to folate starvation. Plant Physiol. 145: 491-503.
110. Loizeau, K., De Brouwer, V., Gambonnet, B., Yu, A., Renou, J. P., Van Der Straeten, D., Lambert, W. E., Rébeillé, F., and Ravanel, S. 2008. A genome-wide and metabolic analysis determined the adaptive response of Arabidopsis cells to folate depletion induced by methotrexate. Plant Physiol. 148: 2083-2095.
111. Lorence, A., Chevone, B. I., Mendes, P., and Nessler, C. L. 2004. Myo-inositol oxygenase offers a possible entry point into plant ascorbate biosynthesis. Plant Physiol. 134: 1200-1205.
112. Lowry, O. H., Bessey, O. A., and Crawford, E. J. 1949. Photolytic and enzymatic transformations of pteroylglutamic acid. J. Biol. Chem. 180: 389-398.
113. Lucock, M., Yates, Z., Glanville, T., Leeming, R., Simpson, N., and Daskalakis, I. 2003. A critical role for B-vitamin nutrition in human developmental and evolutionary biology. Nutr. Res. 23: 1463-1475.
114. Luo, M. Z., Orsi, R., Patrucco, E., Pancaldi, S., and Cella, R. 1997. Multiple transcription start sites of the carrot dihydrofolate reductase thymidylate syn-thase gene, and sub-cellular localization of the bifunctional protein. Plant Mol. Biol. 33: 709-722.
115. Maqbool, S. B., and Christou, P. 1999. Multiple traits of agronomic importance in transgenic indica rice plants: analysis of transgene integration patters, expression levels and stability. Mol. Breed. 5: 471-480.
116. Mathis, J. B., and Brown, G. M. 1980. Dihydroneopterin aldolase from Es-cherichia coli. Methods Enzymol. 66: 556-560.
117. McGuire, J. J., and Coward, J. K. 1984. Pteroylpolyglutamates: biosynthesis, degradation and function. In: Folates and Pterins, Vol. 2. pp. 135-190. Blackley, R. L. and Benkovic, S., Eds., J. Wiley (Interscience), New York.
118. Melse-Boonstra, A., Verhoef, P., Konings, E. J. M., van Dusseldorp, M., Matser, A., Hollman, P. C. H., Meyboom, S., Kok, F. J., and West, C. E. 2002. Influ-ence of processing on Total, monoglutamate and polyglutamate folate contents of leeks, cauliflower, and green beans. J. Agric. Food Chem. 50: 3473-3478.
119. Mills, J. L., Von Kohorn, I., Conley, M. R., Zeller, J. A., Cox, C., Williamson, R. E., and Dufour, D. R. 2003. Low vitamin B-12 concentrations in patients without anemia: the effect of folic acid of grain. Am. J. Clin. Nutr. 77: 1474-1477.
120. Mitsuda, H., and Suzuki, Y. 1971. Enzymatic conversion of 2-amino-4-hydroxy-6-formyl-7,8-dihydropteridine to 2-amino-4-hydroxy-6-hydroxymethyl-7,8-dihydropteridine by cell-free extracts of Escherichia coli B. J. Vitaminol. 17: 5-9.
121. Molloy, A., and Scott, J. 2001. Folates and prevention of disease. Public Health Nutr. 4: 601-609.
122. Moore, L., Bradlee, M., Singer, M., Rothman, K., and Milunsky, A. 2003. Folate intake and the risk of neural tube defects: An estimation of dose-response. Epidemiology 14: 200-205.
123. Morris, M. S., Jacques, P. F., Rosenberg, I. H., and Selhub, J. 2007. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am. J. Clin. Nutr. 85: 193-200.
124. Mouillon, J. M., Ravanel, S., Douce, R., and Rébeillé, F. 2002. Folate synthesis in higher plant mitochondria: coupling between the dihydropterin pyrophosphokinase and the dihydropteroate synthase activities. Biochem.J. 363: 313-319.
125. ′-flanking region to those of the genes encoding wheat high-molecular-weight glutenin and barley D hordein. Gene 170: 223-226.
126. Naqvi, S., Zhu, C., Farre, G., Ramessar, K., Bassie, L., Breitenbach, J., Conesa, D. P., Ros, G., Sandmann, G., Capell, T., and Christou, P. 2009. Transgenic multivitamin corn through biofortification of endosperm with three vitamins representing three distinct metabolic pathways. Proc. Nat. Acad. Sci. USA, 106: 7762-7767.
127. Nare, B., Hardy, L. W., and Beverley, S. M. 1997. The roles of pteridines reductase 1 and dihydrofoloate reductase-thymidylate synthase in pteridines metabolism in the protozoan parasite Leishmania major. J. Biol. Chem. 272: 13883-13891.
128. Neuburger, M., Rébeillé, F., Jourdain, A., Nakamura, S., and Douce, R. 1996. Mitochondria are a major site for folate and thymidylate synthesis in plants. J. Biol. Chem. 271: 9466-9472.
129. Nichols, B. P., Siebold, A. M., and Doktor, S. Z. 1989. Para-aminobenzoate synthesis from chorismate occurs in two steps. J. Biol. Chem. 264: 8597-8601.
130. Noiriel, A., Naponelli, V., Gregory, J. F. III, and Hanson, A. D. 2007a. Pterin and folate salvage. Plants and Escherichia coli lack capacity to reduce oxidized pterins. Plant Physiol. 143: 1101-1109.
131. Noiriel, A., Naponelli, V., Bozzo, G. G., Gregory, J. F. III, and Hanson, A. D. 2007b. Folate salvage in plants: pterin aldehyde reduction is mediated by multiple non-specific aldehyde reductases. Plant J. 51: 378-389.
132. Nunes, A. C. S., Kalkmann, D. C., and Aragão, F. J. L. 2009. Folate bio-fortification of lettuce by expression of a codon optimized chicken GTP cyclohydrolase I gene. Transgenic Res. 18: 661-667.
133. Orsomando, G., Diaz de la Garza, R., Green, B. J., Peng, M., Rea, P. A., Ryan, T. J., Gregory, J. F. III, and Hanson, A. D. 2005. Plant γ-glutamyl hydrolases and folate polyglutamates: characterization, Compartmentation and co-occurrence in vacuoles. J. Biol. Chem. 280: 28877-28884.
134. Orsomando, G., Bozzo, G. G., Diaz de la Garza, R., Basset, G. J., Quinlivan, E. P., Naponelli, V., Rébeillé, F., Ravanel, S., Gregory, J. F. III, and Hanson, A. D. 2006. Evidence for folate-salvage reactions in plants. Plant J. 46: 426-435.
135. Ortiz, P. J. 1970. Dihydrofolate and dihydropteroate synthesis by partially puri-fied enzymes from wild-type and sulfonamide-resistant Pneumococcus. Bio-chemistry 9: 355-361.
136. Ouellette, M., Drummelsmith, J., El Fadili, A., Kundig, C., Richard, D., and Roy, G. 2002. Pterin transport and metabolism in Leishmania and related trypanosomatid parasites. Int. J. Parasitol. 32: 385-398.
137. Peach, C., and Velten, J. 1991. Transgene expression variability (position effect) of CAT and GUS reporter genes driven by linked divergent T-DNA promoters. Plant Mol. Biol. 17: 49-60.
138. Piironen, V., Edelmann, M., Kariluoto, S. and Bed, Z. 2008. Folate in wheat genotypes in the HEALTHGRAIN diversity screen. J. Agric. Food Chem. 56: 9726-9731.
139. Pitcher, R. J., and Edwards, M. C. 1995. The effects of domestic cooking and preparation techniques on the nutritional composition of vegetables. R&D Report No 18, Campden & Chorleywood Food Research Association.
140. Quinlivan, E. P., McPartlin, J., McNulty, H., Ward, M., Strain, J. J., Weir, D. G., and Scott, J. M. 2002. Importance of both folic acid and vitamin B12 in reduction of risk of vascular disease. Lancet 359: 227-228.
141. Quinlivan, E. P., Roje, S., Basset, G., Shachar-Hill, Y., Gregory, J. F. III, and Hanson, A. D. 2003. The folate precursos p-aminobenzoate is reversibly converted to its glucose ester in the plant cytosol. J. Biol. Chem. 278: 20731-20737.
142. Rader, J. I., and Schneeman, B. O. 2006. Prevalence of neural tube defects, folate status, and folate fortification of enriched cereal-grain products in the United States. Pediatrics 11: 71394-1399.
143. Raichaudhuri,A.,Peng,M.,Naponelli,V.,Chen,S.,Sánchez-Fernández,R.,Gu, H., Gregory, J. F.III, Hanson, A. D., and Rea, P. A. 2009. Plant vacuolar ABC transporters that translocate folates and antifolates in vitro and contribute to antifolate tolerance in vivo. J. Biol. Chem. 284: 8449-8460.
144. Ray, J. G., Cole, D. E. C., and Boss, S. C. 2000. An Ontario-wide study of vitamin B12, serum folate, and red cell folate levels in relation to plasma homocysteine: Is a preventable public health issue on the rise? Clin. Biochem. 33: 337-343.
145. Ray, J. G., Vermeulen, M. J., Langman, L. J., Boss, S. C., and Cole, D. E. C. 2003. Persistence of vitamin B12 insufficiency among elderly women after folic acid food fortification. Clin. Biochem. 36: 387-391.
146. Ravanel, S., Cherest, H., Jabrin, S., Grunwald, D., Surdin-Kerjan, Y., Douce, R., and Rébeillé, F. 2001. Tetrahydrofolate biosynthesis in plants: Molecular and functional characterization of dihydrofolate synthetase and three isoforms of folylpolyglutamate synthetase in Arabidopsis thaliana. Proc. Nat. Acad. Sci. U.S.A. 98: 15360-15365.
147. Ravanel, S., Block, M.A., Rippert, P., Jabrin, S., Curien, G., Rébeillé, F., and Douce, R. 2004. Methionine metabolism in plants: chloroplasts are autonomous for de novo methionine synthesis and can import S-adenosylmethionine from the cytosol. J. Biol. Chem. 279: 22548-22557.
148. Razin, A., and Riggs, A. D. 1980. DNA methylation and gene function. Science 210: 604-610.
149. Rébeillé, F., Neuburger, M., and Douce, R. 1994. Interactions between glycine decarboxylase, serine hydroxymethyltransferase and tetrahydrofolate polyg-lutamates in pea leaf mitochondria. Biochem. J. 302: 223-228.
150. Rébeillé, F., Macherel, D., Mouillon, J. M., Garin, J., and Douce, R. 1997. Folate biosynthesis in higher plants: purification and molecular cloning of a bifunctional 6-hydroxymethyl-7,8-dihydropterin pyrophosphokinase/7,8-dihydropteroate synthase localized in mitochondria. EMBO J. 16: 947-957.
151. Rébeillé, F., Ravanel, S., Jabrin, S., Douce, R., Storozhenko, S., and Van Der Straeten, D. 2006. Folates in plants: biosynthesis, distribution and enhancement. Physiol. Plant. 126: 330-342.
152. Reed, L. S., and Archer, M. C. 1980. Oxidation of tetrahydrofolic acid by air. J. Agric. Food Chem. 28: 801-805.
153. Ren, A., Zhang, A., Li, Z., Hao, L., Tian, Y., and Li, Z. 2006. Awareness and use of folic acid, and blood folate concentrations among pregnant women in northern China - An area with a high prevalence of neural tube defects. Reprod Toxicol. 22: 431-436.
154. Roje, S., Wang, H., McNeil, S. D., Raymond, R. K., Appling, D. R., Shachar-Hill, Y., Bohnert, H. J., and Hanson, A. D. 1999. Isolation, characteri-zation, and functional expression of cDNAs encoding NADH-dependent methylenetetrahydrofolate reductase from higher plants. J. Biol. Chem. 274: 36089-36096.
155. Roje, S., Janave, M. T., Ziemak, M. J., and Hanson, A. D. 2002. Cloning and characterization of mitochondrial 5-formyltetrahydrofolate cycloligase from higher plants. J. Biol. Chem. 277: 42748-42754.
156. Roos, A. J., and Cossins, E. A. 1971. Pteroylglutamate derivatives in Pisum sativum L. Biosynthesis of cotyledonary tetrahydropteroylglutamates during germination. Biochem. J. 125: 17-26.
157. Ross, J., Green, J., Baugh, C. M., MacKenzie, R. E., and Matthews, R. G. 1984. Studies on the polyglutamate specificity of methylenetetrahydrofolate dehydrogenase from pig liver. Biochemistry 23: 1796-1801.
158. Sahr, T., Ravanel, S., Basset, G., Nichols, B. P., Hanson, A. D., and Rébeillé, F. 2006. Folatesynthesis in plants:purification,kineticproperties,andinhibition of aminodeoxychorismate synthase. Biochem. J. 396: 157-162.
159. Sanjoaquin, M. A., Allen, N., Couto, E., Roddam, A. W., and Key, T. J. 2005. Folate intake and colorectal cancer risk: a meta-analytical approach. Int. J. Cancer 113: 825-828.
160. Santos, F., Wegkamp, A., de Vos, M. D., Smid, E. J., and Hugenholtz, J. 2008. High-level folate production in fermented foods by the B12 producer Lacto-bacillus reuteri JCM1112. Appl. Environ. Microbiol. 74: 3291-3294.
161. Scholl, T. O., and Johnson, W. G. 2000. Folic acid: influence on the outcome of pregnancy. Am. J. Clin. Nutr. 71: 1295S-1303S.
162. Scott, J. M. 1984. Catabolism of folates. In: Folates and Pterins, Vol. 1. pp. 307-327. Blackley, R. L., and Benkovic, S., Eds., J. Wiley (Interscience), New York.
163. Scott, J. M., and Weir, D. G. 1986. Excretion of folates, pterins and their metabolic products. In: Folates and Pterins, Vol. 3.Nutritional, Pharmacological and Physiological Aspects. pp. 297-324. Blackley, R., Eds., J. Wiley and Sons Inc., New York.
164. Scott, J. M., and Weir, D. G. 1996. Homocysteine and cardiovascular disease. Q. J. Med. 89: 561-563.
165. Scott, J., Rébeillé, F., and Fletcher, J. 2000. Folic acid and folate: the feasibility for nutritional enhancement in plant foods. J. Sci. Food. Agric. 80: 795-824.
166. Seshadri, S., Beiser, A., Selhub, J., Jacques, P. F., Rosenberg, I. H., D'Agostino, R. B., Wilson, P. W. F., and Wolf, P. A. 2002. Plasma homocysteine as a risk factor for dementia and Alzheimer's disease. N. Engl. J. Med. 346: 476-483.
167. Shane, B. 1989. Folylpolyglutamate synthesis and role in the regulation of one-carbon metabolism. Vitam. Horm. 45: 263-335.
168. Shanxi Province Statistical Bureau 2007. Shanxi Statistical Yearbook 2007. Beijing, Shanxi Statistics Press.
169. Sherwood, R. F., Melton, R. G., Alwan, S. M., and Hughes, P. 1985. Purification and properties of carboxypeptidase G2 from Pseudomonas sp. Strain RS-16. Eur. J. Biochem. 148: 447-453.
170. Shin, Y. S., Kim, E. S., Watson, J. E., and Stokstad, E. L. 1975. Studies of folic acid compounds in nature. IV. Folic acid compounds in soybeans and cow milk. Can. J. Biochem. 53: 338-343.
171. Shiota, T. 1959. Enzymic synthesis of folic acid-like compounds by cell-free extracts of Lactobacillus arabinosus. Arch. Biochem. Biophys. 80: 155-161.
172. Shiota, T., Baugh, C. M., Jackson, R., and Dollard, R. 1969. The enzymatic synthesis of hydroxymethyldihydropteridine pyrophosphate and dihydrofolate. Biochemistry 8: 5022-5028.
173. Siehl, D. 1998. The biosynthesis of tryptophan, tyrosine and phenylalanine from chorismate. In: Plant Amino Acids. pp. 171-204. Singh, B. K., Ed., Marcel Dekker Inc., New York.
174. Smith, A. D., and Refsum, H. 2008. Folic acid supplements are good (not bad) for rheumatoid arthritis patients treated with low-dose methotrexate - Reply. Am. J. Clin. Nutr. 88: 480-480.
175. Sohta, Y., Ohta, T., and Masada, M. 1997. Purification and some properties of GTP cyclohydrolase I from spinach leaves. Biosci. Biotech. Biochem. 61: 1081-1085.
176. Song, J., Medline, A., Mason, J. B., Gallinger, S., and Kim, Y. I. 2000a. Effects of dietary folate on intestinal tumorigenesis in the apcMin mouse.Cancer Res. 60: 5434-5440.
177. Song, J., Sohn, K. J., Medline, A., Ash, C., Gallinger, S., and Kim, Y. I. 2000b. Chemopreventive effects of dietary folate on intestinal polyps in Apc+/-Msh2-/- mice. Cancer Res. 60: 3191-3199.
178. Stakhov, L. F., Ladygin, V. G., and Stakhova, L. N. 2002. Effect of ultraviolet C irradiation on folate and free amino acid contents in leaves of Pisum sativum. Biofizika 47: 878-885.
179. Stanger, O. 2004. The potential role of homocysteine in percutaneous coronary interventions (PCI): Review of current evidence and plausibility of action. Cell. Mol. Biol. 50: 953-988.
180. Storozhenko, S., Ravanel, S., Zhang, G. F., Rébeillé, F., Lambert, W., and Van Der Straeten, D. 2005. Folate enhancement in staple crops by metabolic engineering. Trends Food Sci. Technol. 16: 271-281.
181. Storozhenko, S., Navarrete, O., Ravanel, S., De Brouwer, V., Chaerle, P., Zhang, G.-F., Bastien, O., Lambert, W., Rébeillé, F., and Van Der Straeten, D. 2007a. Cytosolic hydroxymethyldihydropterin pyrophosphokinase/dihydropteroate synthase from Arabidopsis thaliana. J. Biol. Chem. 282: 10749-10761.
182. Storozhenko, S., De Brouwer, V., Volckaert, M., Navarrete, O., Blancquaert, D., Zhang, G.-F., Lambert, W., and Van Der Straeten, D. 2007b. Folate fortification of rice by metabolic engineering. Nat. Biotechnol. 25: 1277-1279.
183. Stover, P., and Schirch, V. 1993. The metabolic role of leucovorin. Trends Biochem. Sci. 18: 102-106.
184. Suh, J. R., Oppenheim, E. W., Girgis, S., and Stover, P. J. 2000. Purification and properties of a folate-catabolizing enzyme. J. Biol. Chem. 275: 35646-35655.
185. Suh, J. R., Herbig, A. K., and Stover, P. J. 2001. New perspectives on folate catabolism. Annu. Rev. Nutr. 21: 255-282.
186. Suzuki, Y., and Brown, G. M. 1974. The biosynthesis of folic acid XII. Purification and properties of dihydroneopterin triphosphate pyrophosphohydrolase. J. Biol. Chem. 249: 2405-2410.
187. Swedberg,G.,Castensson,S.,andSköld,O.1979. Characterization of mutationally altered dihydropteroate synthase and its ability to form a sulfonamide-containing dihydrofolate analog. J. Bacteriol. 137: 129-136.
188. Sybesma, W., Starrenburg, M., Kleerebezem, M., Mierau, I.,de Vos, W. M., and Hugenholtz, J. 2003a. Increased production of folate by metabolic engineer-ing of Lactococcus lactis. Appl. Environ. Microbiol. 69: 3069-3076.
189. Sybesma, W., van den Born, E., Starrenburg, M., Mierau, I., Kleerebezem, M., de Vos, W. M., and Hugenholtz, J. 2003b. Controlled modulation of folate polyglutamyl tail length by metabolic engineering of Lactococcus lactis. Appl. Environ. Microbiol. 69: 7101-7107.
190. Takaiwa, F., Oono, K., Wing, D., and Kato, A. 1991. Sequence of three members and expression of a new major subfamily of glutelin genes from rice. Plant. Mol. Biol. 17: 875-885.
191. Tate, P. H., and Bird, A. P. 1993. Effects of DNA methylation on DNA-binding proteins and gene expression. Curr. Opin. Genet. Dev. 3: 226-231.
192. Tewari,Y.B.,Jensen,P.Y.,Kishore,N.,Mayhew,M.P.,Parsons,J.F.,Eisenstein, E., and Goldberg, R. N. 2002. Thermodynamics of reactions catalyzed by PABA synthase. Biophys. Chem. 96: 33-51.
193. Toth, I., Lazar, G., and Goodman, H. M. 1987.Purification and immunochemical characterization of a dihydrofolate-reductase-thymidylate synthase enzyme complex from wild-carrot cells. EMBO J. 6: 1853-1858.
194. Triglia, T., and Cowman, A. F. 1994. Primary structure and expression of the dihydropteroate synthetase gene of Plasmodium falciparum. Proc. Nat. Acad. Sci. U.S.A. 91: 7149-7153.
195. Van Wilder, V., De Brouwer, V., Loizeau, K., Gambonnet, B., Albrieux, C., Van Der Straeten, D., Lambert, W. E., Douce, R., Block, M. A., Rébeillé, F., and Ravanel, S. 2008. C1 metabolism and chlorophyll synthesis: the Mg-protoporphyrin IX methyltransferase activity is dependent on the folate status. New Phytol. 182: 137-145.
196. Vauclare, P., Diallo, N., Bourguignon, J., Macherel, D., and Douce, R. 1996. Regulation of the expression of the glycine decarboxylase complex during pea leaf development. Plant Physiol. 112: 1523-1530.
197. Wald, N. J., Watt, H. C., Law, M. R., Weir, D. G., McPartlin, J., and Scott, J. M. 1998. Homocysteine and ischaemic heart disease: results of a prospec-tive study with implications on prevention. Arch. Intern. Med. 158: 862-867.
198. Wald, D. S., Wald, N. J., Morris, J. K., and Law, M. 2006. Folic acid, homocys-teine, and cardiovascular disease: judging caUSAlity in the face of inconclusive trial evidence. B.M.J. 333:1114-1117.
199. Waller, J. C., Akhtar, T. A., Lara-Núñez, A., Gregory, J. F.III, McQuinn, R. P., Giovannoni, J. J., and Hanson, A. D. 2009. Developmental and feedforward control of the expression of folate biosynthesis genes in tomato fruit. Mol. Plant DOI: 10.1093/mp/ssp057.
200. Wang, J., Leblanc, E., Chang, C.-F., Papadopoulou, B., Bray, T., Whiteley, J. M., Lin, S.-X., and Ouellette, M. 1997. Pterin and folate reduction by the Leishmania tarentolae H locus short-chain dehydrogenase/reductase PTR1. Arch. Biochem. Biophys. 342: 197-202.
201. Ward, M., McNulty, H., McPartlin, J., Strain, J. J., Weir, D. G., and Scott, J. M. 1997. Plasma homocysteine, a risk factor for cardiovascular disease, is lowered by physiological doses of folic acid. Q. J. Med. 90: 519-524.
202. Weaver, L. M., and Herrmann, K. M. 1997. Dynamics of the shikimate pathway in plants. Trends Plants Sci. 2: 346-351.
203. Wegkamp, A., Starrenburg, M., de Vos, W. M., Hugenholtz, J., and Sybesma, W. 2004. Transformation of folate-consuming Lactobacillus gasseri into a folate producer. Appl. Environ. Microbiol. 70: 3146-3148.
204. Wegkamp, A., van Oorschot, W., de Vos, W. M., and Smid, E. J. 2007. Characterization of the role of para-aminobenzoic acid biosynthesis in fo-late production by Lactococcus lactis. Appl. Environ. Microbiol. 73: 2673-2681.
205. Whiteley, J. M., Drais, J., Kirchner, J., and Huennekens, F. M. 1968. Synthesis of 2-amino-4-hydroxy-6-formyl-7,8-dihydropteridine and its identification as a degradation product of dihydrofolate. Arch. Biochem. Biophys. 126: 955-957.
206. Witter, K., Werner, T., Blusch, J. H., Schneider, E. M., Reiss, O., Ziegler, I., Rodl, W., Bacher, A., and Gutlich, M. 1996. Cloning, sequencing and functional studies of the gene encoding human GTP cyclohydrolase I. Gene 171: 285-290.
207. Ye, Q.-Z., Liu, Y., and Walsh, C. T. 1990. p-Aminobenzoate synthesis in Es-cherichia coli: purification and characterization of PabB as aminodeoxycho-rismate synthase and enzyme X as aminodeoxychorismate lyase. Proc. Natl. Acad. Sci. USA 87: 9391-9395.
208. Yoneyama, T., and Hatakeyama, K. 1998. Decameric GTP cyclohydrolase I forms complexes with two pentameric GTPCH feedback regulatory proteins in the presence of phenylalanine or of a combination of BH 4 and GTP. J. Biol. Chem. 273: 20102-20108.
209. Zhang, B., Zhang, T., Lin, L., Wang, F., Xin, R., Gu, X., He, Y., Yu, D., Li, P., Zhang, Q., Zhao, J., Qin, Y., Yang, X., Chen, G., Liu, J., Song, X., and Zheng, X. 2008. Correlation Between Birth Defects and Dietary Nutrition Status in a High Incidence Area of China. Biomed Environ Sci. 21: 37-44.
210. Zhou, J., Kang, S., Wong, P. W. K., Fournier, B., and Rozen, R. 1990. Purification and characterization of methylenetetrahydrofolate reductase from human cadaver liver. Biochem. Med. Metab. Biol. 43: 234-242.
211. Zhu, T., Pan, Z., Domagalski, N., Koepsel, R., Ataai, M. M., and Domach, M. M. 2005. Engineering of Bacillus subtilis for enhanced total synthesis of folic acid. Appl. Environ. Microbiol. 71: 7122-7129.
212. Zrenner, R., Stitt, M., Sonnewald, U., and Boldt, R. 2006. Pyrimidine and purine biosynthesis and degradation in plants. Annu. Rev. Plant Biol. 57: 805-836.