Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1969 Nov;48(11):2032–2037. doi: 10.1172/JCI106168

“Activation” of vitamin D by the liver

G Ponchon 1,2, A L Kennan 1,2, H F DeLuca 1,2
PMCID: PMC297455  PMID: 4310770

Abstract

Isolation of the liver from the circulation of rats eliminates almost completely their ability to convert [1,2]-3H vitamin D3 into its biologically active metabolite, 25-hydroxycholecalciferol, as well as certain other metabolites. It is concluded that the liver is the major if not the only physiologic site of hydroxylation of vitamin D3 (cholecalciferol) into 25-hydroxycholecalciferol.

The osteodystrophy and the higher requirements for vitamin D observed in hepatic insufficiencies may be due to an inability of the liver to transform vitamin D into its metabolically active form.

Full text

PDF
2032

Selected References

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

  1. ALAGILLE D. Retentissement osseux des affections hépato-biliaires chez le nourrison et l'enfant. Bull Mem Soc Med Hop Paris. 1958 Oct 24;74(28-29):717–722. [PubMed] [Google Scholar]
  2. ATKINSON M., NORDIN B. E., SHERLOCK S. Malabsorption and bone disease in prolonged obstructive jaundice. Q J Med. 1956 Jul;25(99):299–312. [PubMed] [Google Scholar]
  3. Avioli L. V., Lee S. W., McDonald J. E., Lund J., DeLuca H. F. Metabolism of vitamin D3-3H in human subjects: distribution in blood, bile, feces, and urine. J Clin Invest. 1967 Jun;46(6):983–992. doi: 10.1172/JCI105605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blunt J. W., DeLuca H. F., Schnoes H. K. 25-hydroxycholecalciferol. A biologically active metabolite of vitamin D3. Biochemistry. 1968 Oct;7(10):3317–3322. doi: 10.1021/bi00850a001. [DOI] [PubMed] [Google Scholar]
  5. Blunt J. W., Tanaka Y., DeLuca H. F. The biological activity of 25-hydroxycholecalciferol, a metabolite of vitamin D3. Proc Natl Acad Sci U S A. 1968 Oct;61(2):717–718. doi: 10.1073/pnas.61.2.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. CHALK K. J., KODICEK E. The association of 14C-labelled vitamin D2 with rat serum proteins. Biochem J. 1961 Apr;79:1–7. doi: 10.1042/bj0790001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. COATES M. E., HOLDSWORTH E. S. Vitamin D3 and absorption of calcium in the chick. Br J Nutr. 1961;15:131–147. doi: 10.1079/bjn19610014. [DOI] [PubMed] [Google Scholar]
  8. COCCHI U. Hepatogene Osteoporosen. Radiol Clin. 1951 Nov;20(6):362–382. [PubMed] [Google Scholar]
  9. Chen P. S., Jr, Lane K. Serum protein binding of vitamin D3. Arch Biochem Biophys. 1965 Oct;112(1):70–75. doi: 10.1016/0003-9861(65)90011-1. [DOI] [PubMed] [Google Scholar]
  10. De Luca H. F., Weller M., Blunt J. W., Neville P. F. Synthesis, biological activity., and metabolism of 22,23-3H vitamin D4. Arch Biochem Biophys. 1968 Mar 20;124(1):122–128. doi: 10.1016/0003-9861(68)90310-x. [DOI] [PubMed] [Google Scholar]
  11. DeLuca H. F. Mechanism of action and metabolic fate of vitamin D. Vitam Horm. 1967;25:315–367. doi: 10.1016/s0083-6729(08)60039-4. [DOI] [PubMed] [Google Scholar]
  12. FRIIS-HANSEN B. Neonatal hepatitis with osteomalacia. Acta Paediatr. 1956 Jul;45(4):376–381. doi: 10.1111/j.1651-2227.1956.tb06886.x. [DOI] [PubMed] [Google Scholar]
  13. GUROFF G., DELUCA H. F., STEENBOCK H. Citrate and action of vitamin D on calcium and phosphorus metabolism. Am J Physiol. 1963 May;204:833–836. doi: 10.1152/ajplegacy.1963.204.5.833. [DOI] [PubMed] [Google Scholar]
  14. Haussler M. R., Myrtle J. F., Norman A. W. The association of a metabolite of vitamin D3 with intestinal mucosa chromatin in vivo. J Biol Chem. 1968 Aug 10;243(15):4055–4064. [PubMed] [Google Scholar]
  15. KELLY R. G., PEETS E. A., GORDON S., BUYSKE D. A. Determination of C-14 and H3 in biological samples by Schoeniger combustion and liquid scintillation techniques. Anal Biochem. 1961 Jun;2:267–273. doi: 10.1016/s0003-2697(61)80010-9. [DOI] [PubMed] [Google Scholar]
  16. KRAHULIK L., SHOOB M. P., MORALES S., SNYDERMAN S. E., HOLT L. E., Jr Congenital obliteration of the bile ducts; with particular reference to dietotherapy. J Pediatr. 1952 Dec;41(6):774–783. doi: 10.1016/s0022-3476(52)80297-5. [DOI] [PubMed] [Google Scholar]
  17. Kehayoglou A. K., Holdsworth C. D., Agnew J. E., Whelton M. J., Sherlock S. Bone disease and calcium absorption in primary biliary cirrhosis with special reference to vitamin-D therapy. Lancet. 1968 Apr 6;1(7545):715–718. doi: 10.1016/s0140-6736(68)92164-8. [DOI] [PubMed] [Google Scholar]
  18. LEVIN E. J. Congenital biliary atresia with emphasis on the skeletal abnormalities. Radiology. 1956 Nov;67(5):714–722. doi: 10.1148/67.5.714. [DOI] [PubMed] [Google Scholar]
  19. LICHTWITZ A., CACHIN M., HIOCO D., TUTIN M., de SEZE [The phosphocalcium syndrome of cirrhosis]. Sem Hop. 1959 Aug 18;35:2399–2409. [PubMed] [Google Scholar]
  20. Lund J., DeLuca H. F. Biologically active metabolite of vitamin D3 from bone, liver, and blood serum. J Lipid Res. 1966 Nov;7(6):739–744. [PubMed] [Google Scholar]
  21. NORMAN A. W., DELUCA H. F. THE PREPARATION OF H3-VITAMINS D2 AND D3--THEIR LOCALIZATION IN THE RAT. Biochemistry. 1963 Sep-Oct;2:1160–1168. doi: 10.1021/bi00905a044. [DOI] [PubMed] [Google Scholar]
  22. NORMAN A. W., LUND J., DELUCA H. F. BIOLOGICALLY ACTIVE FORMS OF VITAMIN D3 IN KIDNEY AND INTESTINE. Arch Biochem Biophys. 1964 Oct;108:12–21. doi: 10.1016/0003-9861(64)90349-2. [DOI] [PubMed] [Google Scholar]
  23. Neville P. F., DeLuca H. F. The synthesis of [1,2-3H]vitamin D3 and the tissue localization of a 0.25-mu-g (10 IU) dose per rat. Biochemistry. 1966 Jul;5(7):2201–2207. doi: 10.1021/bi00871a007. [DOI] [PubMed] [Google Scholar]
  24. Ponchon G., DeLuca H. F. Ethanol-induced artifacts in the metabolism of 3H-vitamin D3. Proc Soc Exp Biol Med. 1969 Jul;131(3):727–731. doi: 10.3181/00379727-131-33962. [DOI] [PubMed] [Google Scholar]
  25. Ponchon G., DeLuca H. F. The role of the liver in the metabolism of vitamin D. J Clin Invest. 1969 Jul;48(7):1273–1279. doi: 10.1172/JCI106093. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. ROBERTS M. H., SULLIVAN C. Influence of the liver on bone metabolism; report of two cases. J Am Med Assoc. 1955 Nov 5;159(10):1002–1007. doi: 10.1001/jama.1955.02960270022006. [DOI] [PubMed] [Google Scholar]
  27. SCHACHTER D., FINKELSTEIN J. D., KOWARSKI S. METABOLISM OF VITAMIN D. I. PREPARATION OF RADIOACTIVE VITAMIN D AND ITS INTESTINAL ABSORPTION IN THE RAT. J Clin Invest. 1964 May;43:787–796. doi: 10.1172/JCI104965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. STEENBOCK H., HERTING D. C. Vitamin D and growth. J Nutr. 1955 Dec 10;57(4):449–468. doi: 10.1093/jn/57.4.449. [DOI] [PubMed] [Google Scholar]
  29. Stohs S. J., DeLuca H. F. Subcellular location of vitamin D and its metabolites in intestinal mucosa after a 10-IU dose. Biochemistry. 1967 Nov;6(11):3338–3349. doi: 10.1021/bi00863a002. [DOI] [PubMed] [Google Scholar]
  30. THOMAS W. C., Jr, MORGAN H. G., CONNOR T. B., HADDOCK L., BILLS C. E., HOWARD J. E. Studies of antiricketic activity in sera from patients with disorders of calcium metabolism and preliminary observations on the mode of transport of vitamin D in human serum. J Clin Invest. 1959 Jul;38(7):1078–1085. doi: 10.1172/JCI103884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thompson G. R., Lewis B., Booth C. C. Absorption of vitamin D3-3H in control subjects and patients with intestinal malabsorption. J Clin Invest. 1966 Jan;45(1):94–102. doi: 10.1172/JCI105327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Trummel C. L., Raisz L. G., Blunt J. W., Deluca H. F. 25-Hydroxycholecalciferol: stimulation of bone resorption in tissue culture. Science. 1969 Mar 28;163(3874):1450–1451. doi: 10.1126/science.163.3874.1450. [DOI] [PubMed] [Google Scholar]
  33. Webling D. D., Holdsworth E. S. The effect of bile, bile acids and detergents on calcium absorption in the chick. Biochem J. 1965 Nov;97(2):408–421. doi: 10.1042/bj0970408. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES