{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T07:03:22Z","timestamp":1790060602972,"version":"4.0.1"},"reference-count":59,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T00:00:00Z","timestamp":1487894400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Vitamin B6 (B6) has a central role in the metabolism of amino acids, which includes important interactions with endogenous redox reactions through its effects on the glutathione peroxidase (GPX) system. In fact, B6-dependent enzymes catalyse most reactions of the transsulfuration pathway, driving homocysteine to cysteine and further into GPX proteins. Considering that mammals metabolize sulfur- and seleno-amino acids similarly, B6 plays an important role in the fate of sulfur-homocysteine and its seleno counterpart between transsulfuration and one-carbon metabolism, especially under oxidative stress conditions. This is particularly important in reproduction because ovarian metabolism may generate an excess of reactive oxygen species (ROS) during the peri-estrus period, which may impair ovulatory functions and early embryo development. Later in gestation, placentation raises embryo oxygen tension and may induce a higher expression of ROS markers and eventually embryo losses. Interestingly, the metabolic accumulation of ROS up-regulates the flow of one-carbon units to transsulfuration and down-regulates remethylation. However, in embryos, the transsulfuration pathway is not functional, making the understanding of the interplay between these two pathways particularly crucial. In this review, the importance of the maternal metabolic status of B6 for the flow of one-carbon units towards both maternal and embryonic GPX systems is discussed. Additionally, B6 effects on GPX activity and gene expression in dams, as well as embryo development, are presented in a pig model under different oxidative stress conditions.<\/jats:p>","DOI":"10.3390\/nu9030189","type":"journal-article","created":{"date-parts":[[2017,2,24]],"date-time":"2017-02-24T06:07:21Z","timestamp":1487916441000},"page":"189","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":99,"title":["Pyridoxine (Vitamin B6) and the Glutathione Peroxidase System; a Link between One-Carbon Metabolism and Antioxidation"],"prefix":"10.3390","volume":"9","author":[{"given":"Danyel","family":"Dalto","sequence":"first","affiliation":[{"name":"Sherbrooke Research Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC J1M 0C8, Canada"},{"name":"Department of Biology, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1K 2R1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Jacques","family":"Matte","sequence":"additional","affiliation":[{"name":"Sherbrooke Research Centre, Agriculture and Agri-Food Canada, Sherbrooke, QC J1M 0C8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,2,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3235","DOI":"10.3390\/nu5083235","article-title":"Methoxistasis: Integrating the roles of homocysteine and folic acid in cardiovascular pathobiology","volume":"5","author":"Joseph","year":"2013","journal-title":"Nutrients"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.mce.2016.06.006","article-title":"One carbon metabolism in pregnancy: Impact on maternal, fetal and neonatal health","volume":"435","author":"Kalhan","year":"2016","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1146\/annurev.nutr.19.1.217","article-title":"Homocysteine metabolism","volume":"19","author":"Selhub","year":"1999","journal-title":"Annu. Rev. Nutr."},{"key":"ref_4","unstructured":"Berg, J.M., Tymoczko, J.L., and Stryer, L. (2002). Biochemistry, W.H. Freeman and Company. [5th ed.]."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"19246","DOI":"10.1074\/jbc.270.33.19246","article-title":"Demonstration that mammalian methionine synthases are predominantly cobalamin-loaded","volume":"270","author":"Chen","year":"1995","journal-title":"J. Biol. Chem."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.abb.2008.01.017","article-title":"Liver betaine-homocysteine S-methyltransferase activity undergoes a redox switch at the active site zinc","volume":"472","author":"Castro","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1093\/hmg\/5.12.1851","article-title":"Cloning, mapping and RNA analysis of the human methionine synthase gene","volume":"5","author":"Li","year":"1996","journal-title":"Hum. Mol. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"13005","DOI":"10.1021\/bi001088w","article-title":"The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes","volume":"39","author":"Mosharov","year":"2000","journal-title":"Biochemistry"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1007\/s00216-001-1117-6","article-title":"Interaction of chemical species with biological regulation of the metabolism of essential trace elements","volume":"372","author":"Windisch","year":"2002","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1006\/abbi.1995.1361","article-title":"Glutathione redox cycle-driven recovery of reduced glutathione after oxidation by tertiary-butyl hydroperoxide in preimplantation mouse embryos","volume":"321","author":"Gardiner","year":"1995","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1093\/ajcn\/81.3.648","article-title":"Dietary vitamin B6 restriction does not alter rates of homocysteine remethylation or synthesis in healthy young women and men","volume":"81","author":"Davis","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3249","DOI":"10.1096\/fj.13-231852","article-title":"Maternal-fetal transfer of selenium in the mouse","volume":"27","author":"Burk","year":"2013","journal-title":"FASEB J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2111","DOI":"10.1016\/S0002-9440(10)64849-3","article-title":"Onset of maternal arterial blood flow and placental oxidative stress. A possible factor in human early pregnancy failure","volume":"157","author":"Jauniaux","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1042\/bj3470291","article-title":"Human cystathionine gamma-lyase: Developmental and in vitro expression of two isoforms","volume":"347","author":"Levonen","year":"2000","journal-title":"Biochem. J."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bender, D.A. (2003). Nutritional Biochemistry of the Vitamins, Cambridge University Press. [2nd ed.].","DOI":"10.1017\/CBO9780511615191"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Combs, G.F. (2012). The Vitamins, Academic Press. [4th ed.].","DOI":"10.1016\/B978-0-12-381980-2.00010-4"},{"key":"ref_17","unstructured":"Combs, G.F. (2008). The Vitamins: Fundamental Aspects in Nutrition and Health, Elsevier."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Berdanier, C.D. (1998). Advanced Nutrition-Micronutrients, CRC Press.","DOI":"10.1201\/9781439821886"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1079\/BJN2000221","article-title":"Effects of long-term parenteral administration of vitamin B6 on B6 status and some aspects of the glucose and protein metabolism of early-weaned piglets","volume":"85","author":"Matte","year":"2001","journal-title":"Br. J. Nutr."},{"key":"ref_20","first-page":"159","article-title":"How pyridoxal 5\u2032-phosphate could function in glycogen phosphorylase catalysis","volume":"3","author":"Helmreich","year":"1992","journal-title":"Biofactors"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1562\/0031-8655(2000)071<0129:SIPVBP>2.0.CO;2","article-title":"Vitamin B6 (pyridoxine) and its derivatives are efficient singlet oxygen quenchers and potential fungal antioxidants","volume":"71","author":"Bilski","year":"2000","journal-title":"Photochem. Photobiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1079\/095442201108729231","article-title":"Modulation of gene expression by vitamin B6","volume":"14","author":"Oka","year":"2001","journal-title":"Nutr. Res. Rev."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/S0083-6729(01)61004-5","article-title":"Biosynthesis of vitamin B6 and structurally related derivatives","volume":"61","author":"Drewke","year":"2001","journal-title":"Vitam. Horm."},{"key":"ref_24","first-page":"1","article-title":"Phylogenetic analyses and comparative genomics of vitamin B6 (pyridoxine) and pyridoxal phosphate biosynthesis pathways","volume":"3","author":"Mittenhuber","year":"2001","journal-title":"J. Mol. Microbiol. Biotechnol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/S0021-9258(19)77322-0","article-title":"Activation of methionine for transmethylation. III. The methionine-activating enzyme of Bakers\u2019 yeast","volume":"231","author":"Mudd","year":"1958","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Ulrey, C.L., Liu, L., Andrews, L.G., and Tollefsbol, T.O. (2005). The impact of metabolism on DNA methylation. Hum. Mol. Genet., 14.","DOI":"10.1093\/hmg\/ddi100"},{"key":"ref_27","first-page":"20","article-title":"Molecular biology of 5,10-methylenetetrahydrofolate reductase","volume":"13","year":"2000","journal-title":"J. Nephrol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1146\/annurev.nutr.012809.104810","article-title":"Compartmentalization of mammalian folate-mediated one-carbon metabolism","volume":"30","author":"Tibbetts","year":"2010","journal-title":"Annu. Rev. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1115","DOI":"10.1093\/jn\/130.5.1115","article-title":"Vitamin B6 deficiency in rats reduces hepatic serine hydroxymethyltransferase and cystathionine beta-synthase activities and rates of in vivo protein turnover, homocysteine remethylation and transsulfuration","volume":"130","author":"Martinez","year":"2000","journal-title":"J. Nutr."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.abb.2007.04.005","article-title":"Effect of vitamin B6 availability on serine hydroxymethyltransferase in MCF-7 cells","volume":"462","author":"Perry","year":"2007","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1002\/hlca.200390329","article-title":"Cobalamin-dependent and cobalamin-independent methionine synthases: Are there two solutions to the same chemical problem?","volume":"86","author":"Matthews","year":"2003","journal-title":"Helv. Chim. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1016\/j.bbapap.2011.03.006","article-title":"The enzymes of the transsulfuration pathways: Active-site characterizations","volume":"1814","author":"Aitken","year":"2011","journal-title":"Biochim. Biophys. Acta Proteins Proteom."},{"key":"ref_33","first-page":"E3845","article-title":"Structural insight into the molecular mechanism of allosteric activation of human cystathionine beta-synthase by S-adenosylmethionine","volume":"111","author":"Majtan","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2212","DOI":"10.1016\/S0021-9258(20)82222-4","article-title":"Cystathionine cleavage enzymes of neurospora","volume":"239","author":"Flavin","year":"1964","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.mam.2008.08.009","article-title":"Structure, function, and post-translational regulation of the catalytic and modifier subunits of glutamate cysteine ligase","volume":"30","author":"Franklin","year":"2009","journal-title":"Mol. Aspects Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"25179","DOI":"10.1074\/jbc.273.39.25179","article-title":"Evidence for heme-mediated redox regulation of human cystathionine \u03b2-synthase activity","volume":"273","author":"Taoka","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S1043-4526(03)47002-2","article-title":"The nutritional significance, metabolism and toxicology of selenomethionine","volume":"47","author":"Schrauzer","year":"2003","journal-title":"Adv. Food Nutr. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/j.jtemb.2015.05.002","article-title":"Interaction between vitamin B6 and source of selenium on the response of the selenium-dependent glutathione peroxidase system to oxidative stress induced by oestrus in pubertal pig","volume":"32","author":"Dalto","year":"2015","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.jtemb.2016.01.001","article-title":"The importance of pyridoxine for the impact of the dietary selenium sources on redox balance, embryo development, and reproductive performance in gilts","volume":"34","author":"Dalto","year":"2016","journal-title":"J. Trace Elem. Med. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1039\/B205802M","article-title":"Trends in selenium biochemistry","volume":"19","author":"Birringer","year":"2002","journal-title":"Nat. Prod. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.taap.2006.09.006","article-title":"Metabolism of 76Se-methylselenocysteine compared with that of 77Se-selenomethionine and 82Se-selenite","volume":"217","author":"Suzuki","year":"2006","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1053","DOI":"10.1016\/j.bbagen.2007.03.007","article-title":"Selenocysteine \u03b2-lyase and methylselenol demethylase in the metabolism of Se-methylated selenocompounds into selenide","volume":"1770","author":"Suzuki","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"4386","DOI":"10.1016\/S0021-9258(18)34734-3","article-title":"Selenocysteine lyase, a novel enzyme that specifically acts on selenocysteine. Mammalian distribution and purification and properties of pig liver enzyme","volume":"257","author":"Esaki","year":"1982","journal-title":"J. Biol. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1080\/10408399709527773","article-title":"Selenium in health and disease: A review","volume":"37","author":"Foster","year":"1997","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_45","first-page":"96","article-title":"Biosynthesis of selenocysteine on its tRNA in eukaryotes","volume":"5","author":"Xu","year":"2007","journal-title":"PLoS Biol."},{"key":"ref_46","first-page":"346","article-title":"Selenium regulation of selenium-dependent glutathione peroxidases in animals and transfected CHO cells","volume":"10","author":"Sunde","year":"1997","journal-title":"Biomed. Environ. Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.bbagen.2005.05.010","article-title":"Selenocysteine in proteins\u2014Properties and biotechnological use","volume":"1726","author":"Johansson","year":"2005","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/0304-4165(77)90153-2","article-title":"Biosynthesis of dimethyl selenide from sodium selenite in rat liver and kidney cell-free systems","volume":"497","author":"Hsieh","year":"1977","journal-title":"Biochim. Biophys. Acta Gen. Subj."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1021\/bi00867a039","article-title":"Enzymic synthesis of dimethyl selenide from sodium selenite in mouse liver extracts","volume":"5","author":"Ganther","year":"1966","journal-title":"Biochemistry"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"942","DOI":"10.2527\/2001.794942x","article-title":"Comparative effects of high dietary levels of organic and inorganic selenium on selenium toxicity of growing-finishing pigs","volume":"79","author":"Kim","year":"2001","journal-title":"J. Anim. Sci."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"231","DOI":"10.2527\/jas.2010-3340","article-title":"Effect of dietary organic and inorganic selenium on antioxidant status, embryo development, and reproductive performance in hyperovulatory first-parity gilts","volume":"90","author":"Fortier","year":"2012","journal-title":"J. Anim. Sci."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1002\/mnfr.200700353","article-title":"Effect of selenium status and supplementation with high-selenium yeast on plasma homocysteine and B vitamin concentrations in the UK elderly","volume":"52","author":"Bekaert","year":"2008","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1093\/jn\/136.2.373","article-title":"Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women","volume":"136","author":"Davis","year":"2006","journal-title":"J. Nutr."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1093\/jn\/136.8.2141","article-title":"Vitamin B-6 deficiency suppresses the hepatic transsulfuration pathway but increases glutathione concentration in rats fed AIN-76A or AIN-93G diets","volume":"136","author":"Lima","year":"2006","journal-title":"J. Nutr."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1089\/ars.2010.3586","article-title":"Glutathione peroxidase-1 in health and disease: From molecular mechanisms to therapeutic opportunities","volume":"5","author":"Lubos","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1530\/REP-14-0408","article-title":"Gene expression of porcine blastocysts from gilts fed organic or inorganic selenium and pyridoxine","volume":"149","author":"Dalto","year":"2015","journal-title":"Reproduction"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"515","DOI":"10.2754\/avb200877040515","article-title":"Efficacy of selenium from Se-enriched yeast on selenium transfer from sows to piglets","volume":"77","author":"Svoboda","year":"2008","journal-title":"Acta Vet. Brno"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5540","DOI":"10.2527\/jas.2014-7590","article-title":"Effect of inorganic or organic selenium supplementation on reproductive performance and tissue trace mineral concentrations in gravid first-parity gilts, fetuses, and nursing piglets","volume":"92","author":"Ma","year":"2014","journal-title":"J. Anim. Sci."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/biof.5520100225","article-title":"Vitamin B6 enzymes participating in selenium amino acid metabolism","volume":"10","author":"Soda","year":"1999","journal-title":"BioFactors"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/3\/189\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T18:29:05Z","timestamp":1760207345000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/9\/3\/189"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,2,24]]},"references-count":59,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2017,3]]}},"alternative-id":["nu9030189"],"URL":"https:\/\/doi.org\/10.3390\/nu9030189","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,2,24]]}}}