Figure 8. The Metabolic Activation of Vitamin D. Abbreviations: 25-D, 25-hydroxyvitamin D; 1,25-dihydroxyvitamin D; VDR, vitamin D receptor. Vitamin D from the diet or the conversion from precursors in skin through ultraviolet radiation (light) provides the substrate of the indicated steps in metabolic activation. The pathways apply to both the endogenous animal form of vitamin D (vitamin D3, cholecalciferol) and the exogenous plant form of vitamin D (vitamin D2, ergocalciferol), both of which are present in humans at a ratio of approximately 2:1. In the kidney, 25-D is also converted to 24-hydroxylated metabolites which seem generally inactive but may have unique effects on chondrogenesis and intramembranous ossification. The many effects (Table 8) of vitamin D metabolites are mediated through nuclear receptors or effects on target-cell membranes (see Acknowledgments).