Vitamin B6: A Long Known Compound of Surprising Complexity

Springer Science and Business Media LLC - Tập 14 Số 1 - Trang 329-351
Sutton Mooney1, Jan-Erik Leuendorf2, Christopher L. Hendrickson3, Hanjo Hellmann2
1School of Biological Sciences, Washington State University, Pullman, WA, USA
2washington state university
3Free University of Berlin

Tóm tắt

In recent years vitamin B6 has become a focus of research describing the compound’s critical function in cellular metabolism and stress response. For many years the sole function of vitamin B6 was considered to be that of an enzymatic cofactor. However, recently it became clear that it is also a potent antioxidant that effectively quenches reactive oxygen species and is thus of high importance for cellular well-being. In view of the recent findings, the current review takes a look back and summarizes the discovery of vitamin B6 and the elucidation of its structure and biosynthetic pathways. It provides a detailed overview on vitamin B6 both as a cofactor and a protective compound. Besides these general characteristics of the vitamin, the review also outlines the current literature on vitamin B6 derivatives and elaborates on recent findings that provide new insights into transport and catabolism of the compound and on its impact on human health.

Từ khóa


Tài liệu tham khảo

Ohdake, 1932, Isolation of "Oryzanin" (Antineuritic Vitamin) from Rice-polishings, Bull. Agri. Chem. Soc. Japan., 8, 11, 10.1080/03758397.1932.10856984

Wiardy, 1938, Crystalline Vitamin B6 (Adermin), Nature, 142, 1158, 10.1038/1421158b0

1934, Vitamin B2 and the Pellagra-like Dermatitis in Rats, Nature, 133, 498, 10.1038/133498a0

1938, Crystalline vitamin B6, J. Am. Chem. Soc., 60, 983, 10.1021/ja01271a505

Ichiba, 1938, Cristalline vitamin B6, Sci. Pap. Inst. Phys. Chem. Res., 34, 623

Keresztesy, 1938, Vitamin B-6, Proc. Soc. Exp. Biol. Med., 38, 64, 10.3181/00379727-38-9740P

Kuhn, 1938, Über das antidermatitische Vitamin der Hefe, Ber. Chem. Ges., 71, 780, 10.1002/cber.19380710415

Lepkovsky (1938). Crystalline factor I. Science, 87, 169–170.

Eckardt, 1939, Vitamin B6 and Skin Lesions in Rats, Nature, 144, 512, 10.1038/144512a0

Harris, 1939, Synthetic vitamin B6, Science, 89, 347, 10.1126/science.89.2311.347

Snell, 1942, Occurrence in natural products of a physiologically active metabolite of pyridoxine, J. Biol. Chem., 143, 519, 10.1016/S0021-9258(18)72641-0

Drewke, 2001, Biosynthesis of vitamin B6 and structurally related derivatives, Vitam. Horm., 61, 121, 10.1016/S0083-6729(01)61004-5

Mittenhuber, 2001, Phylogenetic analyses and comparative genomics of vitamin B6 (pyridoxine) and pyridoxal phosphate biosynthesis pathways, J. Mol. Microbiol.Biotechnol., 3, 1

Grogan, 1988, Temperature-sensitive murein synthesis in an Escherichia coli pdx mutant and the role of alanine racemase, Arc. Microbiol., 150, 363, 10.1007/BF00408308

Nakamura, 2004, Structure, function, and dietary regulation of delta-6, delta-5, and delta-9 desaturases, Annu. Rev. Nutr., 24, 345, 10.1146/annurev.nutr.24.121803.063211

Horrobin, 1993, Fatty acid metabolism in health and disease: the role of delta-6-desaturase, Am. J. Clin. Nutr., 57, 732S, 10.1093/ajcn/57.5.732S

Helmreich, 1992, How pyridoxal 5'-phosphate could function in glycogen phosphorylase catalysis, Biofactors, 3, 159

Cheltsov, 2003, Circular permutation of 5-aminolevulinate synthase: effect on folding, conformational stability, and structure, J. Biol. Chem., 278, 27945, 10.1074/jbc.M207011200

Rottmann, 1991, 1-aminocyclopropane-1-carboxylate synthase in tomato is encoded by a multigene family whose transcription is induced during fruit and floral senescence, J. Mol. Biol., 222, 937, 10.1016/0022-2836(91)90587-V

Bilski, 2000, Vitamin B6 (Pyridoxine) and Its Derivatives Are Efficient Singlet Oxygen Quenchers and Potential Fungal Antioxidants, Photochem. Photobiol., 71, 129, 10.1562/0031-8655(2000)071<0129:SIPVBP>2.0.CO;2

Chen, 2005, Pyridoxine is required for post-embryonic root development and tolerance to osmotic and oxidative stresses, Plant J., 44, 396, 10.1111/j.1365-313X.2005.02538.x

Hill, 1996, The biogenetic anatomy of vitamin B6. A 13C NMR investigation of the biosynthesis of pyridoxol in Escherichia coli, J. Biol. Chem., 271, 30426, 10.1074/jbc.271.48.30426

Arenz, 1996, Occurrence of neurotoxic 4'-O-methylpyridoxine in Ginkgo biloba leaves, Ginkgo medications and Japanese Ginkgo food, Planta Med., 62, 548, 10.1055/s-2006-957967

Drewke, 1993, Growth response to 4-hydroxy-L-threonine of Escherichia coli mutants blocked in vitamin B6 biosynthesis, FEBS Lett., 318, 125, 10.1016/0014-5793(93)80005-F

Laber, 1999, Vitamin B6 biosynthesis: formation of pyridoxine 5'-phosphate from 4-(phosphohydroxy)-L-threonine and 1-deoxy-D-xylulose-5-phosphate by PdxA and PdxJ protein, FEBS Lett., 449, 45, 10.1016/S0014-5793(99)00393-2

Cane, 1998, Biosynthesis of Vitamin B6: The Oxidation of 4-(Phosphohydroxy)-l-threonine by PdxA, J. Am. Chem. Soc., 120, 1936, 10.1021/ja9742085

Lam, 1992, Characterization of the complex pdxH-tyrS operon of Escherichia coli K-12 and pleiotropic phenotypes caused by pdxH insertion mutations, J. Bacteriol., 174, 6033, 10.1128/jb.174.19.6033-6045.1992

Zhao, 1996, 4-Phospho-hydroxy-L-threonine is an obligatory intermediate in pyridoxal 5'-phosphate coenzyme biosynthesis in Escherichia coli K-12, FEMS Microbiol. Lett., 135, 275

Sivaraman, 2003, Crystal structure of Escherichia coli PdxA, an enzyme involved in the pyridoxal phosphate biosynthesis pathway, J. Biol. Chem., 278, 43682, 10.1074/jbc.M306344200

Notheis, 1995, Purification and characterization of the pyridoxol-5'-phosphate: oxygen oxidoreductase (deaminating) from Escherichia coli, Biochim. Biophys. Acta, 1247, 265, 10.1016/0167-4838(94)00235-9

Sprenger, 1997, Identification of a thiamin-dependent synthase in Escherichia coli required for the formation of the 1-deoxy-D-xylulose 5-phosphate precursor to isoprenoids, thiamin, and pyridoxol, Proc. Natl. Acad. Sci. USA, 94, 12857, 10.1073/pnas.94.24.12857

Franco, 2001, Structural basis for the function of pyridoxine 5'-phosphate synthase, Structure, 9, 245, 10.1016/S0969-2126(01)00584-6

Burns, 2005, Reconstitution and biochemical characterization of a new pyridoxal-5'-phosphate biosynthetic pathway, J. Am. Chem. Soc., 127, 3682, 10.1021/ja042792t

Titiz, 2005, Vitamin B6 biosynthesis in higher plants, Proc. Natl. Acad. Sci. USA, 102, 13687, 10.1073/pnas.0506228102

Ehrenshaft, 1999, A highly conserved sequence is a novel gene involved in de novo vitamin B6 biosynthesis, Proc. Natl. Acad. Sci. USA, 96, 9374, 10.1073/pnas.96.16.9374

Gengenbacher, 2006, Vitamin B6 biosynthesis by the malaria parasite Plasmodium falciparum: biochemical and structural insights, J. Biol. Chem., 281, 3633, 10.1074/jbc.M508696200

Zhu, 2005, A new arrangement of (beta/alpha)8 barrels in the synthase subunit of PLP synthase, J. Biol. Chem., 280, 27914, 10.1074/jbc.M503642200

Tews, 2007, Functional analysis of PDX2 from Arabidopsis, a glutaminase involved in vitamin B6 biosynthesis, Plant Physiol., 144, 915, 10.1104/pp.107.096784

Zein, 2006, Structural insights into the mechanism of the PLP synthase holoenzyme from Thermotoga maritima, Biochemistry, 45, 14609, 10.1021/bi061464y

Flicker, 2007, Structural and thermodynamic insights into the assembly of the heteromeric pyridoxal phosphate synthase from Plasmodium falciparum, J. Mol. Biol., 374, 732, 10.1016/j.jmb.2007.09.038

Yang, 1998, Identification and function of the pdxY gene, which encodes a novel pyridoxal kinase involved in the salvage pathway of pyridoxal 5'-phosphate biosynthesis in Escherichia coli K-12, J. Bacteriol., 180, 1814, 10.1128/JB.180.7.1814-1821.1998

Yang, 1996, Identification of the pdxK gene that encodes pyridoxine (vitamin B6) kinase in Escherichia coli K-12, FEMS Microbiol. Lett., 141, 89, 10.1111/j.1574-6968.1996.tb08368.x

Cao, 2006, Crystal structure of human pyridoxal kinase, J. Struct. Biol., 154, 327, 10.1016/j.jsb.2006.02.008

Li, 2002, Crystal structure of brain pyridoxal kinase, a novel member of the ribokinase superfamily, J. Biol. Chem., 277, 46385, 10.1074/jbc.M208600200

Safo, 2006, Crystal structure of pyridoxal kinase from the Escherichia coli pdxK gene: implications for the classification of pyridoxal kinases, J. Bacteriol., 188, 4542, 10.1128/JB.00122-06

Safo, 2004, Crystal structure of the PdxY Protein from Escherichia coli, J. Bacteriol., 186, 8074, 10.1128/JB.186.23.8074-8082.2004

Musayev, 2007, Crystal Structure of human pyridoxal kinase: structural basis of M(+) and M(2+) activation, Protein Sci., 16, 2184, 10.1110/ps.073022107

Zhao, 1995, Kinetic limitation and cellular amount of pyridoxine (pyridoxamine) 5'-phosphate oxidase of Escherichia coli K-12, J. Bacteriol., 177, 883, 10.1128/jb.177.4.883-891.1995

Loubbardi, 1995, Sterol uptake induced by an impairment of pyridoxal phosphate synthesis in Saccharomyces cerevisiae: cloning and sequencing of the PDX3 gene encoding pyridoxine (pyridoxamine) phosphate oxidase, J. Bacteriol., 177, 1817, 10.1128/jb.177.7.1817-1823.1995

Sang, 2007, Identification of a pyridoxine (pyridoxamine) 5'-phosphate oxidase from Arabidopsis thaliana, FEBS Lett., 581, 344, 10.1016/j.febslet.2006.12.028

Pedelacq, 2006, Crystal structure of a putative pyridoxine 5'-phosphate oxidase (Rv2607) from Mycobacterium tuberculosis, Proteins, 62, 563, 10.1002/prot.20824

Biswal, 2006, The molecular structure of Rv2074, a probable pyridoxine 5'-phosphate oxidase from Mycobacterium tuberculosis, at 1.6 angstroms resolution, Acta Crystallogr. Sect. F Struct. Biol. Cryst. Commun., 62, 735, 10.1107/S1744309106025012

Safo, 2003, Structure and mechanism of Escherichia coli pyridoxine 5'-phosphate oxidase, Biochim. Biophys. Acta, 1647, 76, 10.1016/S1570-9639(03)00060-8

Fonda, 1991, The binding of pyridoxal 5'-phosphate to human serum albumin, Arch. Biochem. Biophys., 288, 79, 10.1016/0003-9861(91)90167-H

Li, 1974, Regulation of pyridoxal 5'-phosphate metabolism in liver, Biochem. Biophys. Res. Commun., 61, 677, 10.1016/0006-291X(74)91010-9

Lumeng, 1974, Pyridoxal 5'-phosphate in plasma: source, protein-binding, and cellular transport, J. Lab. Clin. Med., 84, 334

Harris, 1990, The human alkaline phosphatases: what we know and what we don't know, Clin. Chim. Acta, 186, 133, 10.1016/0009-8981(90)90031-M

Bull, 2002, Acid phosphatases, Mol. Pathol., 55, 65, 10.1136/mp.55.2.65

Lee, 2008, Human brain pyridoxal-5'-phosphate phosphatase (PLPP):protein transduction of PEP-1-PLPP into PC12 cells, BMB Rep., 41, 408, 10.5483/BMBRep.2008.41.5.408

Jang, 2003, Human pyridoxal phosphatase. Molecular cloning, functional expression, and tissue distribution, J. Biol. Chem., 278, 50040, 10.1074/jbc.M309619200

Fonda, 1992, Purification and characterization of vitamin B6-phosphate phosphatase from human erythrocytes, J. Biol. Chem., 267, 15978, 10.1016/S0021-9258(19)49630-0

Mukherjee, 2007, PLP catabolism: identification of the 4-pyridoxic acid dehydrogenase gene in Mesorhizobium loti MAFF303099, Bioorg. Chem., 35, 458, 10.1016/j.bioorg.2007.07.003

Yagi, 1983, The bacterial oxidation of vitamin B6. 4-Pyridoxic acid dehydrogenase: a membrane-bound enzyme from Pseudomonas MA-1, J. Biol. Chem., 258, 9419, 10.1016/S0021-9258(17)44684-9

Burg, 1960, Bacterial oxidation of vitamin B6. II. Metabolites of pyridoxamine, J. Biol. Chem., 235, 1164, 10.1016/S0021-9258(18)69498-0

Fukuwatari, 2008, Age-related alterations of B-group vitamin contents in urine, blood and liver from rats, J. Nutr. Sci. Vitaminol. (Tokyo), 54, 357, 10.3177/jnsv.54.357

Rybak, 2004, Clinical analysis of vitamin B(6): determination of pyridoxal 5'-phosphate and 4-pyridoxic acid in human serum by reversed-phase high-performance liquid chromatography with chlorite postcolumn derivatization, Anal. Biochem., 333, 336, 10.1016/j.ab.2004.06.036

Pearl, 2003, Succinic semialdehyde dehydrogenase deficiency in children and adults, Ann. Neurol., 54, S73, 10.1002/ana.10629

Mulligan, 1976, Transport and metabolism of vitamin B6 in Salmonella typhimurium LT2, J. Biol. Chem., 251, 1052, 10.1016/S0021-9258(17)33800-0

Shane, 1976, Transport and metabolism of vitamin B6 in the yeast Saccharomyces carlsbergensis 4228, J. Biol. Chem., 251, 1042, 10.1016/S0021-9258(17)33799-7

Zhang, 1991, Uptake of N-(4'-pyridoxyl) amines and release of amines by renal cells: a model for transporter-enhanced delivery of bioactive compounds, Proc. Natl. Acad. Sci. USA, 88, 10407, 10.1073/pnas.88.23.10407

Said, 2008, Pyridoxine uptake by colonocytes: a specific and regulated carrier-mediated process, Am. J. Physiol. Cell. Physiol., 294, C1192, 10.1152/ajpcell.00015.2008

Said, 2003, A carrier-mediated mechanism for pyridoxine uptake by human intestinal epithelial Caco-2 cells: regulation by a PKA-mediated pathway, Am. J. Physiol. Cell. Physiol., 285, C1219, 10.1152/ajpcell.00204.2003

Schenker, 1992, Human placental vitamin B6 (pyridoxal) transport: normal characteristics and effects of ethanol, Am. J. Physiol., 262, R966

Hirose, 2000, Efflux system for pyridoxine in Schizosaccharomyces pombe, Biosci. Biotechnol. Biochem., 64, 2675, 10.1271/bbb.64.2675

Yagi, 1998, Growth phase-dependent active transport of pyridoxine in a fission yeast, Schizosaccharomyces pombe, FEMS Microbiol. Lett., 161, 145, 10.1111/j.1574-6968.1998.tb12941.x

Morita, 2004, Disruption of the plr1+ gene encoding pyridoxal reductase of Schizosaccharomyces pombe, J. Biochem., 135, 225, 10.1093/jb/mvh026

Stolz, 2003, Tpn1p, the plasma membrane vitamin B6 transporter of Saccharomyces cerevisiae, J. Biol. Chem., 278, 18990, 10.1074/jbc.M300949200

Stolz, 2005, Amiloride uptake and toxicity in fission yeast are caused by the pyridoxine transporter encoded by bsu1+ (car1+), Eukaryot. Cell., 4, 319, 10.1128/EC.4.2.319-326.2005

Rodionov, 2009, A Novel Class of Modular Transporters for Vitamins in Prokaryotes, J. Bacteriol., 191, 42, 10.1128/JB.01208-08

Ehrenshaft, 1998, SOR1, a gene required for photosensitizer and singlet oxygen resistance in Cercospora fungi, is highly conserved in divergent organisms, Mol. Cell., 1, 603, 10.1016/S1097-2765(00)80060-X

Ehrenshaft, 1999, Functional characterization of SOR1, a gene required for resistance to photosensitizing toxins in the fungus Cercospora nicotianae, Curr. Genet., 34, 478, 10.1007/s002940050423

Bilski, 2000, Vitamin B6 (pyridoxine) and its derivatives are efficient singlet oxygen quenchers and potential fungal antioxidants, Photochem. Photobiol., 71, 129, 10.1562/0031-8655(2000)071<0129:SIPVBP>2.0.CO;2

Bilski, 2002, Direct detection of singlet oxygen via its phosphorescence from cellular and fungal cultures, Meth. Enzymol., 352, 41, 10.1016/S0076-6879(02)52005-X

Graham, 2004, A highly conserved gene for vitamin B biosynthesis may have consequences for stress and hormone responses in plants, Physiol. Plant., 121, 8, 10.1111/j.0031-9317.2004.00283.x

Chen, 2005, Pyridoxine is required for post-embryonic root development and tolerance to osmotic and oxidative stresses, Plant J., 44, 396, 10.1111/j.1365-313X.2005.02538.x

Titiz, 2006, PDX1 is essential for vitamin B6 biosynthesis, development and stress tolerance in Arabidopsis, Plant J., 48, 933, 10.1111/j.1365-313X.2006.02928.x

Shi, 2002, The Arabidopsis salt overly sensitive 4 mutants uncover a critical role for vitamin B6 in plant salt tolerance, Plant Cell, 14, 575, 10.1105/tpc.010417

Wagner, 2006, Analysis of the Arabidopsis rsr4-1/pdx1-3 mutant reveals the critical function of the PDX1 protein family in metabolism, development, and vitamin B6 biosynthesis, Plant Cell, 18, 1722, 10.1105/tpc.105.036269

Leuendorf, 2008, The Pdx1 family is structurally and functionally conserved between Arabidopsis thaliana and Ginkgo biloba, Febs J., 275, 960, 10.1111/j.1742-4658.2008.06275.x

Gonzalez, 2007, Vitamer levels, stress response, enzyme activity, and gene regulation of Arabidopsis lines mutant in the pyridoxine/pyridoxamine 5'-phosphate oxidase (PDX3) and the pyridoxal kinase (SOS4) genes involved in the vitamin B6 salvage pathway, Plant Physiol., 145, 985, 10.1104/pp.107.105189

Antelmann, 1997, First steps from a two-dimensional protein index towards a response-regulation map for Bacillus subtilis, Electrophoresis, 18, 1451, 10.1002/elps.1150180820

Savenstrand, 2004, Ultraviolet-B signalling: Arabidopsis brassinosteroid mutants are defective in UV-B regulated defence gene expression, Plant Physiol. Biochem., 42, 687, 10.1016/j.plaphy.2004.06.011

Osmani, 1999, The extremely conserved pyroA gene of Aspergillus nidulans is required for pyridoxine synthesis and is required indirectly for resistance to photosensitizers, J. Biol. Chem., 274, 23565, 10.1074/jbc.274.33.23565

Padilla, 1998, The highly conserved, coregulated SNO and SNZ gene families in Saccharomyces cerevisiae respond to nutrient limitation, J. Bacteriol., 180, 5718, 10.1128/JB.180.21.5718-5726.1998

Braun, 1996, A stationary-phase gene in Saccharomyces cerevisiae is a member of a novel, highly conserved gene family, J. Bacteriol., 178, 6865, 10.1128/jb.178.23.6865-6872.1996

Denslow, 2007, Regulation of the Arabidopsis thaliana vitamin B6 biosynthesis genes by abiotic stress, Plant Physiol. Biochem., 45, 152, 10.1016/j.plaphy.2007.01.007

Hallmen, 2007, The human pyridoxal kinase, a plausible target for ginkgotoxin from Ginkgo biloba, Febs J., 274, 1036, 10.1111/j.1742-4658.2007.05654.x

Arenz, 1996, Occurrence of Neurotoxic 4'-O-Methylpyridoxine in Ginkgo biloba Leaves, Ginkgo Medications and Japanese Ginkgo Food, Planta Med., 62, 548, 10.1055/s-2006-957967

Fiehe, 2000, Biosynthesis of 4'-O-methylpyridoxine (Ginkgotoxin) from primary precursors, J. Nat. Prod., 63, 185, 10.1021/np990414+

Wada, 1985, An antivitamin B6, 4'-methoxypyridoxine, from the seed of Ginkgo biloba L., Chem. Pharm. Bull. (Tokyo), 33, 3555, 10.1248/cpb.33.3555

Buss, 2001, Properties and interaction of heterologously expressed glutamate decarboxylase isoenzymes GAD(65kDa) and GAD(67kDa) from human brain with ginkgotoxin and its 5'-phosphate, J. Med. Chem., 44, 3166, 10.1021/jm010868f

Higuchi, 2006, Aminophospholipid glycation and its inhibitor screening system: a new role of pyridoxal 5'-phosphate as the inhibitor, J. Lipid Res., 47, 964, 10.1194/jlr.M500348-JLR200

Coatrieux, 2008, Advanced lipid peroxidation end products in oxidative damage to proteins. Potential role in diseases and therapeutic prospects for the inhibitors, Br. J. Pharmacol., 153, 6, 10.1038/sj.bjp.0707395

Metz, 2003, Pyridoxamine, an inhibitor of advanced glycation and lipoxidation reactions: a novel therapy for treatment of diabetic complications, Arch. Biochem. Biophys., 419, 41, 10.1016/j.abb.2003.08.021

Metz, 2003, Pyridoxamine traps intermediates in lipid peroxidation reactions in vivo: evidence on the role of lipids in chemical modification of protein and development of diabetic complications, J. Biol. Chem., 278, 42012, 10.1074/jbc.M304292200

Voziyan, 2002, A post-Amadori inhibitor pyridoxamine also inhibits chemical modification of proteins by scavenging carbonyl intermediates of carbohydrate and lipid degradation, J. Biol. Chem., 277, 3397, 10.1074/jbc.M109935200

Booth, 1997, In vitro kinetic studies of formation of antigenic advanced glycation end products (AGEs). Novel inhibition of post-Amadori glycation pathways, J. Biol. Chem., 272, 5430, 10.1074/jbc.272.9.5430

Booth, 1996, Thiamine pyrophosphate and pyridoxamine inhibit the formation of antigenic advanced glycation end-products: comparison with aminoguanidine, Biochem. Biophys. Res. Commun., 220, 113, 10.1006/bbrc.1996.0366

Mackey, 2004, Uptake, hydrolysis, and metabolism of pyridoxine-5'-beta-D-glucoside in Caco-2 cells, J. Nutr., 134, 842, 10.1093/jn/134.4.842

Gregory, 1987, Identification and quantification of pyridoxine-β-glucoside as a major form of vitamin B-6 in plant-derived foods, J. Agric. Food Chem., 35, 76, 10.1021/jf00073a018

Opassiri, 2004, Beta-glucosidase, exo-beta-glucanase and pyridoxine transglucosylase activities of rice BGlu1, Biochem. J., 379, 125, 10.1042/bj20031485

Suzuki, 1998, Formation of 5'-0-(β-D-Glucopyranosyl) pyridoxine in soybean seedlings and suspension cells cultured in the presence of pyridoxine, Bull. Res. Inst. Bioresour. Okayama Univ., 5, 107

Scott, 2000, Analysis of Ginkgo biloba for the presence of ginkgotoxin and ginkgotoxin 5'-glucoside, J. AOAC Int., 83, 1313, 10.1093/jaoac/83.6.1313

Suzuki, 1997, Formation of beta-galactosides of pyridoxine using Sporobolomyces singularis, Methods Enzymol., 280, 71, 10.1016/S0076-6879(97)80103-6

Suzuki, 1993, Formation of beta-fructosyl compounds of pyridoxine in growing culture of Aspergillus niger, Biosci. Biotechnol. Biochem., 57, 875, 10.1271/bbb.57.875

Opassiri, 2006, Analysis of rice glycosyl hydrolase family 1 and expression of Os4bglu12 beta-glucosidase, BMC Plant Biol., 6, 33, 10.1186/1471-2229-6-33

Nakano, 1995, Pyridoxine and pyridoxine-5'-beta-D-glucoside exert different effects on tissue B-6 vitamers but similar effects on beta-glucosidase activity in rats, J. Nutr., 125, 2751

Trumbo, 1990, Hydrolysis of pyridoxine-5'-beta-D-glucoside by a broad-specificity beta-glucosidase from mammalian tissues, Proc. Soc. Exp. Biol. Med., 195, 240, 10.3181/00379727-195-43142

Perry, 2007, Evidence of GLP-1-mediated neuroprotection in an animal model of pyridoxine-induced peripheral sensory neuropathy, Exp. Neurol., 203, 293, 10.1016/j.expneurol.2006.09.028

Albin, 1987, Acute sensory neuropathy-neuronopathy from pyridoxine overdose, Neurology, 37, 1729, 10.1212/WNL.37.11.1729

Lu, 2008, Supplementing vitamin B6 to a low vitamin B6 diet exaggerates UVB-Induced skin tumorigenesis in DMBA-treated hairless mice, J. Nutr. Sci. Vitaminol. (Tokyo), 54, 262, 10.3177/jnsv.54.262

Wondrak, 2004, 3-hydroxypyridine chromophores are endogenous sensitizers of photooxidative stress in human skin cells, J. Biol. Chem., 279, 30009, 10.1074/jbc.M404379200

Maeda, 2000, Vitamin B6 phototoxicity induced by UVA radiation, Arch. Dermatol. Res., 292, 562, 10.1007/s004030000174

Theodoratou, 2008, Dietary vitamin B6 intake and the risk of colorectal cancer, Cancer Epidemiol. Biomarkers Prev., 17, 171, 10.1158/1055-9965.EPI-07-0621

Tsao, 2007, Oxidant stress and B vitamins status in patients with non-small cell lung cancer, Nutr. Cancer., 59, 8, 10.1080/01635580701365043

Chinapaw, 2008, Walking or vitamin B for cognition in older adults with mild cognitive impairment? A randomised controlled trial, Br. J. Sports Med., 42, 344, 10.1136/bjsm.2007.044735

Chin, 2007, The effect of walking and vitamin B supplementation on quality of life in community-dwelling adults with mild cognitive impairment: a randomized, controlled trial, Qual.Life Res., 16, 1137, 10.1007/s11136-007-9219-z

Luchsinger, 2007, Relation of higher folate intake to lower risk of Alzheimer disease in the elderly, Arch. Neurol., 64, 86, 10.1001/archneur.64.1.86

Balk, 2007, Vitamin B6, B12, and folic acid supplementation and cognitive function: a systematic review of randomized trials, Arch. Intern. Med., 167, 21, 10.1001/archinte.167.1.21

Ford, 2008, Vitamins B12, B6, and folic acid for onset of depressive symptoms in older men: results from a 2-year placebo-controlled randomized trial, J. Clin. Psychiatry, 69, 1203, 10.4088/JCP.v69n0801

Merete, 2008, Vitamin B6 is associated with depressive symptomatology in Massachusetts elders, J. Am. Coll. Nutr., 27, 421, 10.1080/07315724.2008.10719720

Miodownik, 2008, Pyridoxal plasma level in schizophrenic and schizoaffective patients with and without tardive dyskinesia, Clin. Neuropharmacol., 31, 197, 10.1097/WNF.0b013e3181506623

Lerner, 2007, Vitamin B6 treatment for tardive dyskinesia: a randomized, double-blind, placebo-controlled, crossover study, J. Clin. Psychiatry, 68, 1648, 10.4088/JCP.v68n1103

Miodownik, 2006, Vitamin B6 versus mianserin and placebo in acute neuroleptic-induced akathisia: a randomized, double-blind, controlled study, Clin. Neuropharmacol., 29, 68, 10.1097/00002826-200603000-00002

Rimland, B., and Edelson, S.M. (2005). Parent ratings of behavior effects of biomedical interventions, Autism Research Institute.

Audhya, T. (, 2002). Laboratory indices of vitamin and mineral deficiency in autism. Presented at Defeat Autism Now!, San Diego, California, USA.

Lonn, 2006, Homocysteine lowering with folic acid and B vitamins in vascular disease, N. Engl. J. Med., 354, 1567, 10.1056/NEJMoa060900

Ishihara, 2008, Intake of folate, vitamin B6 and vitamin B12 and the risk of CHD: the Japan Public Health Center-Based Prospective Study Cohort I, J. Am. Coll. Nutr., 27, 127, 10.1080/07315724.2008.10719684

Albert, 2008, Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial, JAMA, 299, 2027, 10.1001/jama.299.17.2027

Herrmann, 2007, Stimulation of osteoclast activity by low B-vitamin concentrations, Bone, 41, 584, 10.1016/j.bone.2007.06.005

Toyota, 1981, The endocrine pancreas in pyridoxine deficient rats, Tohoku J. Exp. Med., 134, 331, 10.1620/tjem.134.331

Jain, 2007, Vitamin B6 (pyridoxamine) supplementation and complications of diabetes, Metabolism, 56, 168, 10.1016/j.metabol.2006.09.002

MacKenzie, 2006, Folate and vitamin B6 rapidly normalize endothelial dysfunction in children with type 1 diabetes mellitus, Pediatrics, 118, 242, 10.1542/peds.2005-2143

Denslow, 2007, Regulation of the Arabidopsis thaliana vitamin B(6) biosynthesis genes by abiotic stress, Plant Physiol. Biochem., 2, 152, 10.1016/j.plaphy.2007.01.007

Musayev, 2003, Structure and properties of recombinant human pyridoxine 5'-phosphate oxidase, Protein Sci., 12, 1455, 10.1110/ps.0356203

Zhao, 1995, Kinetic limitation and cellular amount of pyridoxine (pyridoxamine) 5'-phosphate oxidase of Escherichia coli K-12, J. Bacteriol., 177, 883, 10.1128/jb.177.4.883-891.1995

Cailleux, 1997, Mechanisms of the inhibition of human erythrocyte pyridoxal kinase by drugs, Biochem. Pharmacol., 54, 863, 10.1016/S0006-2952(97)00252-9

Hanna, 1997, Human pyridoxal kinase. cDNA cloning, expression, and modulation by ligands of the benzodiazepine receptor, J. Biol. Chem., 272, 10756, 10.1074/jbc.272.16.10756

Li, 2002, Crystallization and preliminary crystallographic studies of pyridoxal kinase from sheep brain, Acta Crystallogr. D. Biol. Crystallogr., 58, 1479, 10.1107/S0907444902011034