A B S T R A C T Isolation of the liver from the circulation of rats eliminates almost completely their ability to convert [1,2] metabolite, 25-hydroxycholecalciferol (1, 2). This substance is more active than vitamin D3 itself in curing rickets when administered in vivo and acts more rapidly in stimulating the intestinal absorption of calcium as well as mobilization of bone (3).

A B S T R A C T The metabolism of vitamin D3 has been studied after intravenous injection of 10 IU of [1,2-3H]-vitamin Da to vitamin D-deficient rats. The disappearance of the radioactivity from the plasma follows a very peculiar pattern characterized by an early rapid disappearance followed by a rebound of radioactivity before assuming still a third rather slow disappearance rate. The "rebound" phenomenon is concomitant with a rapid release of the radioactivity from the liver and is accounted for by the appearance of 25-hydroxycholecalciferol and other metabolites in the blood. It is postulated that the liver is the major site of transformation of vitamin D3 into 25-hydroxycholecalciferol.

This metabolite is 0.5 as active as vitamin D3 in the rat in the cure of rickets and in intestinal calcium transport, but is more active than vitamin D3 in the mobilization of bone mineral. DeLuca, 1969;Blunt et al., 1968b) (peak IV). This substance was subsequently isolated in pure form and identified as 25-hydroxycholecalciferol (Blunt et al., 1968a,b). It was successfully synthesized chemically and shown to be the circulating active form of the vitamin (DeLuca, 1969).Synthesis of [3H]-25-hydroxycholecalciferol made possible the demonstration that this metabolite is further metabolized to more polar metabolites in intestine, bone, and kidney (Cousins et al., 1970; R. J. Cousins and H. F. DeLuca, 1970, unpublished data). Haussler et al. (1968) and Lawson et al. (1969) have also shown a metabolite of vitamin D3 in intestinal nuclei more polar than 25-hydroxycholecalciferol.Thus the identification of these metabolites appeared important to a thorough understanding of the mechanism of vitamin D action. One of these polar metabolites has now been isolated in pure form, identified as 21,25-dihydroxycholecalciferol, and shown to have a marked action on mobilization of bone mineral while having a small but significant effect on intestinal calcium transport. In addition it is one-half as active as vitamin D3 in curing rickets in rats. It is the purpose of this communication to report these results. Methods and ResultsGeneral Procedures. All radioactive determinations were carried out by means of a Packard Tri-Carb Model 3003 liquid scintillation counter equipped with an automatic biochemistry, vol.

No abstract

No abstract