(23S)-1,23,25-Trihydroxyvitamin D3: its biologic activity and role in 1 alpha,25-dihydroxyvitamin D3 26,23-lactone biosynthesis.
(23S)-1,23,25-Trihydroxyvitamin D3 was isolated from bovine kidney homogenates incubated with 1,25-dihydroxyvitamin D3 by sequential chromatography through one Sephadex LH-20 column and three high-performance liquid chromatography systems. Ultraviolet absorption spectroscopy and mass spectrometry confirmed the structural assignment. One high-performance liquid chromatography system separated the R and S epimers of 1,23,25-trihydroxyvitamin D3 and indicated that the natural product had the S configuration. Plasma pharmacokinetic studies in rats showed that (23S)-1,23,25-trihydroxy[3H]vitamin D3 was rapidly cleared from plasma (t1/2 = 60 min). 1 alpha,25-Dihydroxy[3H]vitamin D3 26,23-lactone appeared concurrently with the disappearance of (23S)-1,23,25-trihydroxy[3H]vitamin D3. Experiments with radioinert compounds showed that 1,25-dihydroxyvitamin D3 and (23S)-1,23,25-trihydroxyvitamin D3 were efficient precursors to 1,25-dihydroxyvitamin D3 26,23-lactone both in intact and in nephrectomized rats. (25S)-1,25,26-Trihydroxyvitamin D3, however, was ineffective at raising plasma 1,25-dihydroxyvitamin D3 26,23-lactone concentrations. These results confirm the presence of extrarenal 1,25-dihydroxyvitamin D3 23(S)-hydroxylase(s) and demonstrate that C-23 hydroxylation of 1,25-dihydroxyvitamin D3 precedes C-26 hydroxylation in the formation of 1,25-dihydroxyvitamin D3 26,23-lactone. (23S)-1,23,25-Trihydroxyvitamin D3 had no intestinal calcium absorptive or bone calcium resorptive activity when dosed to vitamin D deficient rats at levels up to 500 ng. C-23 oxidation, therefore, appears to be a physiologic pathway of 1,25-(OH)2D3 metabolism and a major pathway for the deactivation of pharmacologic levels of 1,25-dihydroxyvitamin D3.
D000818:Animals; D001842:Bone and Bones / Q000378:metabolism; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000097:blood / Q000302:isolation & purification / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002417:Cattle; D007408:Intestinal Absorption; D007668:Kidney / Q000032:analysis; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D051381:Rats; D011919:Rats, Inbred Strains
C026947:1,25-dihydroxyvitamin D3-26,23-lactone; C038789:1,23,25-trihydroxyvitamin D3; D002117:Calcitriol; D002118:Calcium