Vitamin D: recent advances

HF DeLuca, HK Schnoes - Annual review of biochemistry, 1983 - annualreviews.org
HF DeLuca, HK Schnoes
Annual review of biochemistry, 1983annualreviews.org
The field of vitamin D metabolism and mechanism of action has continued to be very active.
Autoradiography has shown specific nuclear localization of 1, 25-(OH) 2D3 in target organs
prior to initiation of mechanism of action. Specific nuclear localization has also been
demonstrated in a variety of other tissues not previously appreciated as targets of vitamin D
action, suggesting the possibility that vitamin D carries out subtle functions previously
unappreciated. A macromolecule believed to be a receptor that specifically binds 1, 35 …
The field of vitamin D metabolism and mechanism of action has continued to be very active. Autoradiography has shown specific nuclear localization of 1, 25-(OH) 2D3 in target organs prior to initiation of mechanism of action. Specific nuclear localization has also been demonstrated in a variety of other tissues not previously appreciated as targets of vitamin D action, suggesting the possibility that vitamin D carries out subtle functions previously unappreciated. A macromolecule believed to be a receptor that specifically binds 1, 35-(OHhD3 has been found in the cells showing nuclear localization and in a number of tumor and cancer cell lines. Since 1, 25-(OH) 2D3 has been found to cause differentiation of certain myeloid leukemia cells, a possible relationship between the vitamin D system and cancer has appeared. Substantial evidence exists that 1, 25-(OHhD3 func tions in a nuclear-mediated process, although some evidence exists that not all of the actions of 1, 2S-(OHhD3 are carried out through such a mechanism. Substantial advances in our understanding of the metabolism of vitamin D have also been made. The presence of significant amounts of 10 (hydroxylase has been located in the placenta in addition to the kidney. Although there have been reports of extrarenal synthesis of 1, 25-(OHhD3'these sites, ifthey produce 1, 25-(OHhD3, produce it in insufficient amounts for function. The renal la-hydroxylase has been solubilized and shown to be a three-component system. The 25-hydroxylase in the liver has also been solubilized and shown to be a two-component mixed-function mono oxygenase. New pathways of vitamin D metabolism include a 23-oxidation to form 23, 25-(OH) 2D3 or a 23-hydroxylated form of 1, 25-(OH) 2D3. 23, 25-(OH) 2D3 is further oxidized to produce a 25-(OHhD3-26, 23-lactone. Although these pathways are of significant magnitude, their roles remain unknown since the products have low biological activity. Important analogs of the vitamin D metabolites include 24, 24-F 2-25-OH D3 and the 26, 26, 26, 27, 27, 27-F 6-25-0H-D3. These have been used to show that the 24-hydroxylation, the 26-hydroxylation, and the lactone formation do not play a significant role in the function of vitamin D. Their I-hydroxy analogs have also been prepared and shown to be extremely biologically active, being somewhere around ten times more active than the native 1, 25-dihydroxyvitamin D3, illustrating that important analogs of the vitamin D system continue to be discovered.
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