This is the summary of a book chapter we contributed recently and that is under review. The book entitled, Vitamin D: Oxidation, Immunity & Aging is going to be published by Taylor and Francis.
Vitamin D plays a central role in modulating calcium and phosphate homeostasis in the body. However, its role in many other physiological and disease states, primarily those of chronic nature, such as diabetes, cancer, Alzheimer’s among others is also widely known. While the effects of its principal stimulatory metabolite, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is studied extensively in many physiological and disease states, research results have now emerged suggesting the possible biological role for another metabolite, 24,25-dihydroxyvitamin D3 [24,25(OH)2D3]. Actions of 1,25(OH)2D3 on Ca2+ and Pi homeostasis are believed to be mediated by both pre-genomic and genomic pathways involving the classical vitamin D receptor and the more recently identified 1,25D3-MARRS (membrane associated, rapid response steroid binding) receptor, also known as PDIA3/ERp57/GRp58/ERp60/ERp61. The metabolite 24,25(OH)2D3 is made when an animal is vitamin D replete and provides an endogenous feedback loop for intestinal phosphate absorption. It acts to decrease the specific activity of the antioxidative enzyme catalase, resulting in higher levels of H2O2. Hydrogen peroxide in turn acts at two points: oxidation of the 1,25D3-MARRS receptor as well as inhibition of protein kinase C. These effects can be overcome with diets supplemented with antioxidants. Here we discuss these two recently identified putative receptors for vitamin D metabolites, their role in relation to Ca2+ and Pi transport, and the role of reactive oxygen species in relation to oxidative stress that is usually associated with chronic diseases along with a brief overview of 25-hydroxyvitamin D3 [25(OH)D3] as a functional metabolite.
