Defects in the synthesis and metabolism of vitamin D

Summary

It is now recognized that it is casual exposure to sunlight that provides most humans with their vitamin D requirement. During exposure to sunlight, the high energy ultraviolet B photons (290—315 mm) photolyzes cutaneous stores of 7-dehydrocholesterol to previtamin D₃. Once formed, previtamin D₃ undergoes a thermal isomerization that results in the formation of vitamin D₃. Vitamin D₃ is biologically inert and requires successive hydroxylations in the liver and kidney to form its biologically active hormone 1,25-dihydroxyvitamin D₃ The major physiologic function of 1,25-dihydroxy-vitamin D₃ is to maintain blood calcium in the normal range. It accomplishes this by increasing the efficiency of intestinal calcium absorption and mobilizing stem cells to become osteoclasts which, inturn, remove calcium from the bone. It is now recognized that there are a variety of calcium metabolic disorders that are related to defects in the synthesis and metabolism of vitamin D. Chronic granulomatous disorders are often associated with hypercalciuria and hypercalcemia. The mechanism by which this occurs is that activated macrophages within granulomatous tissue, in an unregulated manner, convert 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. Besides its calcemic activity 1,25-dihydroxyvitamin D₃ is a potent antiprolfierative factor for cells and tissues that possess its vitamin D receptor. This has clinical utility in that 1,25-dihydroxyvitamin D₃ and its analogs have been successfully used for the treatment of the hyperproliferative skin disease psoriasis.

Key words

Vitamin D - 1,25-Dihydroxyvitamin D - 25-OH-D-l-Hydroxylase - sarcoidosis - psoriasis