Is there more to learn about functional vitamin D metabolism?

The state of information on the enzymes responsible for the conversion of vitamin D3 to 1α,25-dhydroxyvitamin D3 (1,25-(OH)2D3), the metabolic active form responsible for the well-known function of vitamin D on calcium metabolism and bone mineralization has been briefly reviewed. There remains an unidentified enzyme responsible for 25% of the 25-hydroxylation of vitamin D3, while 75% of serum 25-hydroxyvitamin D3 (25-OH-D3) arises from CYP2R1. The well-established suppression of multiple sclerosis (MS) by sunlight has been confirmed using the mouse model, experimental autoimmune encephalomyelitis (EAE). This suppression results from a narrow band of ultraviolet light (300-315nm) that does not increase serum 25-OH-D3. Thus, UV light suppresses EAE by a mechanism not involving vitamin D. Vitamin D deficiency unexpectedly suppresses the development of EAE. Further, vitamin D receptor knockout in susceptible mice also prevents the development of EAE. On the other hand, deletion of CYP2R1 and the 1α-hydroxylase, CYP27B1, does not impair the development of EAE. Thus, either vitamin D itself or a heretofore-unknown metabolite is needed for the development of a component of the immune system necessary for development of EAE. This article is part of a Special Issue entitled '17th Vitamin D Workshop'.