Pyridoxine (Vitamin B₆) and the Glutathione Peroxidase System; a Link between One-Carbon Metabolism and Antioxidation.

Abstract

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.