Mineral Metabolism in Health and Disease

The elucidation of the metabolism of vitamin D has increased our understanding of mineral homeostasis. Vitamin D is produced in the skin as cholecalciferol (vitamin D3) and is absorbed in the small bowel as both vitamin D3 and D2 (ergocalciferol). Since the parent compound cannot be readily measured, estimates of vitamin D stores are made from assays of the circulating 25-hydroxy metabolites. In normal individuals, dermal synthesis seems to be much more important than the diet as a source of vitamin D. Circulating 25(OH)D3 is more abundant than 25(OH)D2 even in the winter and despite vitamin D2 dietary supplementation (Poskitt et al., 1979). Since vitamin D2 and D3 are hydroxylated at a comparable rate (Whyte et al., 1979), this implies that dermal synthesis is more important than diet in normal circumstances. Similarly, 25(OH)D levels correlate, not with dietary intake, but rather with recorded sunlight and season of the year (Stryd et al., 1979). Conversion to 25(OH)D occurs mainly in the microsomal fraction of the liver. This conversion is inhibited mainly by the liver and plasma pool of vitamin D and 25(OH)D, rather than by calcium and phosphate (Bhattacharya and DeLuca, 1973; Mawer, 1977). Control is not rigorous, however, and 25(OH)D levels do reflect provision of parent vitamin D to the liver. By contrast, the circulating levels of the 1,25(OH)2D metabolites do not correlate well with nutritional vitamin D status and are normal or low with vitamin D loading (Hughes et al., 1976). Circulating levels of 25(OH)D are 10–40 ng/ml in the United States, depending on season and latitude, and lower in Great Britain. 25(OH)D undergoes enterohepatic circulation (Arnaud et al., 1975), but the significance of this observation remains unclear; possibly, enhanced delivery to the intestine facilitates 24-hydroxylation (see below).