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Vitamin D: recent advances.
Annu Rev Biochem. 1983; 52:411-39.AR

Abstract

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-(OH)2D3 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-(OH)2D3 functions in a nuclear-mediated process, although some evidence exists that not all of the actions of 1,25-(OH)2D3 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 1 alpha-hydroxylase has been located in the placenta in addition to the kidney. Although there have been reports of extrarenal synthesis of 1,25-(OH)2D3, these sites, if they produce 1,25-(OH)2D3, produce it in insufficient amounts for function. The renal 1 alpha-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 monooxygenase. 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-(OH)2D3-26,23-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-F2-25-OH-D3 and the 26,26,26,27,27,27-F6-25-OH-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 1-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.

Authors

No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

6311080

Citation

DeLuca, H F., and H K. Schnoes. "Vitamin D: Recent Advances." Annual Review of Biochemistry, vol. 52, 1983, pp. 411-39.
DeLuca HF, Schnoes HK. Vitamin D: recent advances. Annu Rev Biochem. 1983;52:411-39.
DeLuca, H. F., & Schnoes, H. K. (1983). Vitamin D: recent advances. Annual Review of Biochemistry, 52, 411-39.
DeLuca HF, Schnoes HK. Vitamin D: Recent Advances. Annu Rev Biochem. 1983;52:411-39. PubMed PMID: 6311080.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D: recent advances. AU - DeLuca,H F, AU - Schnoes,H K, PY - 1983/1/1/pubmed PY - 1983/1/1/medline PY - 1983/1/1/entrez SP - 411 EP - 39 JF - Annual review of biochemistry JO - Annu. Rev. Biochem. VL - 52 N2 - 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-(OH)2D3 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-(OH)2D3 functions in a nuclear-mediated process, although some evidence exists that not all of the actions of 1,25-(OH)2D3 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 1 alpha-hydroxylase has been located in the placenta in addition to the kidney. Although there have been reports of extrarenal synthesis of 1,25-(OH)2D3, these sites, if they produce 1,25-(OH)2D3, produce it in insufficient amounts for function. The renal 1 alpha-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 monooxygenase. 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-(OH)2D3-26,23-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-F2-25-OH-D3 and the 26,26,26,27,27,27-F6-25-OH-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 1-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. SN - 0066-4154 UR - https://www.unboundmedicine.com/medline/citation/6311080/Vitamin_D:_recent_advances_ L2 - http://arjournals.annualreviews.org/doi/full/10.1146/annurev.bi.52.070183.002211?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -