Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1989 Aug 15;262(1):173–180. doi: 10.1042/bj2620173

Target cell metabolism of 1,25-dihydroxyvitamin D3 to calcitroic acid. Evidence for a pathway in kidney and bone involving 24-oxidation.

G Makin 1, D Lohnes 1, V Byford 1, R Ray 1, G Jones 1
PMCID: PMC1133244  PMID: 2818561

Abstract

1,25-dihydroxyvitamin D3 is converted to calcitroic acid before being excreted in the bile. Biosynthesis of calcitroic acid has been demonstrated in two target cells of vitamin D, in the kidney and the osteoblastic cell line UMR-106. Calcitroic acid was identified by combinations of h.p.l.c., u.v. spectroscopy and mass spectrometry. Evidence is presented that calcitroate is derived from the 24-oxidation pathway, possibly through the intermediate 24,25,26,27-tetranor-1,23-dihydroxyvitamin D3. The 24-oxidation pathway to calcitroic acid in bone cells is stimulated by 1,25-dihydroxyvitamin D3. The pathway in both bone cells and perfused kidney operates at physiological concentrations of substrate and appears to be capable of rapid clearance of the hormone.

Full text

PDF
173

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. BLIGH E. G., DYER W. J. A rapid method of total lipid extraction and purification. Can J Biochem Physiol. 1959 Aug;37(8):911–917. doi: 10.1139/o59-099. [DOI] [PubMed] [Google Scholar]
  2. Chandler J. S., Chandler S. K., Pike J. W., Haussler M. R. 1,25-Dihydroxyvitamin D3 induces 25-hydroxyvitamin D3-24-hydroxylase in a cultured monkey kidney cell line (LLC-MK2) apparently deficient in the high affinity receptor for the hormone. J Biol Chem. 1984 Feb 25;259(4):2214–2222. [PubMed] [Google Scholar]
  3. Esvelt R. P., De Luca H. F. Calcitroic acid: biological activity and tissue distribution studies. Arch Biochem Biophys. 1981 Feb;206(2):403–413. doi: 10.1016/0003-9861(81)90107-7. [DOI] [PubMed] [Google Scholar]
  4. Esvelt R. P., Schnoes H. K., DeLuca H. F. Isolation and characterization of 1 alpha-hydroxy-23-carboxytetranorvitamin D: a major metabolite of 1,25-dihydroxyvitamin D3. Biochemistry. 1979 Sep 4;18(18):3977–3983. doi: 10.1021/bi00585a021. [DOI] [PubMed] [Google Scholar]
  5. Fraser D. R., Kodicek E. Unique biosynthesis by kidney of a biological active vitamin D metabolite. Nature. 1970 Nov 21;228(5273):764–766. doi: 10.1038/228764a0. [DOI] [PubMed] [Google Scholar]
  6. Harnden D., Kumar R., Holick M. F., Deluca H. F. Side chain metabolism of 25-hydroxy-[26,27-14C] vitamin D3 and 1,25-dihydroxy-[26,27-14C] vitamin D3 in vivo. Science. 1976 Aug 6;193(4252):493–494. doi: 10.1126/science.941020. [DOI] [PubMed] [Google Scholar]
  7. Haussler M. R. Vitamin D receptors: nature and function. Annu Rev Nutr. 1986;6:527–562. doi: 10.1146/annurev.nu.06.070186.002523. [DOI] [PubMed] [Google Scholar]
  8. Holick M. F., Kleiner-Bossaller A., Schnoes H. K., Kasten P. M., Boyle I. T., DeLuca H. F. 1,24,25-Trihydroxyvitamin D3. A metabolite of vitamin D3 effective on intestine. J Biol Chem. 1973 Oct 10;248(19):6691–6696. [PubMed] [Google Scholar]
  9. Holick S. A., Holick M. F., MacLaughlin J. A. Chemical synthesis of [1 beta-3H] 1 alpha, 25-dihydroxyvitamin D3 and [1 alpha-3H] 1 beta, 25-dihydroxyvitamin D2: biological activity of 1 beta, 25-dihydroxyvitamin D3. Biochem Biophys Res Commun. 1980 Dec 16;97(3):1031–1037. doi: 10.1016/0006-291x(80)91479-5. [DOI] [PubMed] [Google Scholar]
  10. Jones G. A new pathway of 25-hydroxyvitamin D3 metabolism. Methods Enzymol. 1986;123:141–154. doi: 10.1016/s0076-6879(86)23017-7. [DOI] [PubMed] [Google Scholar]
  11. Jones G. Chromatographic separation of 24(R),25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3-26,23-lactone using a cyano-bonded phase packing. J Chromatogr. 1983 Aug 12;276(1):69–75. [PubMed] [Google Scholar]
  12. Jones G., Kung M., Kano K. The isolation and identification of two new metabolites of 25-hydroxyvitamin D3 produced in the kidney. J Biol Chem. 1983 Nov 10;258(21):12920–12928. [PubMed] [Google Scholar]
  13. Jones G., Vriezen D., Lohnes D., Palda V., Edwards N. S. Side-chain hydroxylation of vitamin D3 and its physiological implications. Steroids. 1987 Jan-Mar;49(1-3):29–53. doi: 10.1016/0039-128x(87)90078-x. [DOI] [PubMed] [Google Scholar]
  14. Lohnes D., Jones G. Side chain metabolism of vitamin D3 in osteosarcoma cell line UMR-106. Characterization of products. J Biol Chem. 1987 Oct 25;262(30):14394–14401. [PubMed] [Google Scholar]
  15. Mayer E., Bishop J. E., Chandraratna R. A., Okamura W. H., Kruse J. R., Popjak G., Ohnuma N., Norman A. W. Isolation and identification of 1,25-dihydroxy-24-oxo-vitamin D3 and 1,23,25-trihydroxy-24-oxo-vitamin D3. New metabolites of vitamin D3 produced by a C-24 oxidation pathway of metabolism for 1,25-dihydroxyvitamin D3 present in intestine and kidney. J Biol Chem. 1983 Nov 25;258(22):13458–13465. [PubMed] [Google Scholar]
  16. Mayer E., Bishop J. E., Ohnuma N., Norman A. W. Biological activity assessment of the vitamin D metabolites 1,25-dihydroxy-24-oxo-vitamin D3 and 1,23,25-trihydroxy-24-oxo-vitamin D3. Arch Biochem Biophys. 1983 Jul 15;224(2):671–676. doi: 10.1016/0003-9861(83)90254-0. [DOI] [PubMed] [Google Scholar]
  17. McDonnell D. P., Mangelsdorf D. J., Pike J. W., Haussler M. R., O'Malley B. W. Molecular cloning of complementary DNA encoding the avian receptor for vitamin D. Science. 1987 Mar 6;235(4793):1214–1217. doi: 10.1126/science.3029866. [DOI] [PubMed] [Google Scholar]
  18. Napoli J. L., Horst R. L. C(24)- and C(23)-oxidation, converging pathways of intestinal 1,25-dihydroxyvitamin D3 metabolism: identification of 24-keto-1,23,25-trihydroxyvitamin D3. Biochemistry. 1983 Dec 6;22(25):5848–5853. doi: 10.1021/bi00294a025. [DOI] [PubMed] [Google Scholar]
  19. Napoli J. L., Pramanik B. C., Royal P. M., Reinhardt T. A., Horst R. L. Intestinal synthesis of 24-keto-1,25-dihydroxyvitamin D3. A metabolite formed in vivo with high affinity for the vitamin D cytosolic receptor. J Biol Chem. 1983 Aug 10;258(15):9100–9107. [PubMed] [Google Scholar]
  20. Nemere I., Yoshimoto Y., Norman A. W. Calcium transport in perfused duodena from normal chicks: enhancement within fourteen minutes of exposure to 1,25-dihydroxyvitamin D3. Endocrinology. 1984 Oct;115(4):1476–1483. doi: 10.1210/endo-115-4-1476. [DOI] [PubMed] [Google Scholar]
  21. Partridge N. C., Frampton R. J., Eisman J. A., Michelangeli V. P., Elms E., Bradley T. R., Martin T. J. Receptors for 1,25(OH)2-vitamin D3 enriched in cloned osteoblast-like rat osteogenic sarcoma cells. FEBS Lett. 1980 Jun 16;115(1):139–142. doi: 10.1016/0014-5793(80)80744-7. [DOI] [PubMed] [Google Scholar]
  22. Price P. A., Baukol S. A. 1,25-Dihydroxyvitamin D3 increases synthesis of the vitamin K-dependent bone protein by osteosarcoma cells. J Biol Chem. 1980 Dec 25;255(24):11660–11663. [PubMed] [Google Scholar]
  23. Reddy G. S., Jones G., Kooh S. W., Fraser D. Inhibition of 25-hydroxyvitamin D3-1-hydroxylase by chronic metabolic acidosis. Am J Physiol. 1982 Oct;243(4):E265–E271. doi: 10.1152/ajpendo.1982.243.4.E265. [DOI] [PubMed] [Google Scholar]
  24. Reddy G. S., Tserng K. Y., Thomas B. R., Dayal R., Norman A. W. Isolation and identification of 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3, a new metabolite of 1,25-dihydroxyvitamin D3 produced in rat kidney. Biochemistry. 1987 Jan 13;26(1):324–331. doi: 10.1021/bi00375a045. [DOI] [PubMed] [Google Scholar]
  25. Rosenthal A. M., Jones G., Kooh S. W., Fraser D. 25-hydroxyvitamin D3 metabolism by isolated perfused rat kidney. Am J Physiol. 1980 Jul;239(1):E12–E20. doi: 10.1152/ajpendo.1980.239.1.E12. [DOI] [PubMed] [Google Scholar]
  26. Tanaka Y., Deluca H. F., Schnoes H. K., Ikekawa N., Kobayashi Y. 24,24-difluoro-1,25-dihydroxyvitamin D3: in vitro production, isolation, and biological activity. Arch Biochem Biophys. 1980 Feb;199(2):473–478. doi: 10.1016/0003-9861(80)90304-5. [DOI] [PubMed] [Google Scholar]
  27. Tenenhouse H. S., Yip A., Jones G. Increased renal catabolism of 1,25-dihydroxyvitamin D3 in murine X-linked hypophosphatemic rickets. J Clin Invest. 1988 Feb;81(2):461–465. doi: 10.1172/JCI113342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Yamada S., Nakayama K., Takayama H., Shinki T., Takasaki Y., Suda T. Isolation, identification, and metabolism of (23S,25R)-25-hydroxyvitamin D3 26,23-lactol. A biosynthetic precursor of (23S,25R)-25-hydroxyvitamin D3 26,23-lactone. J Biol Chem. 1984 Jan 25;259(2):884–889. [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES