Isotopic labeling affects 1,25-dihydroxyvitamin D metabolism.
Isotope substitution can change the biochemical properties of vitamin D. To determine the effect of substituting 3H for 1H on the metabolism of 1,25(OH)2D3, we measured the metabolic clearance rate and renal metabolism of unlabeled and 3H-labeled 1,25(OH)2D3. Substitution of 3H for 1H on carbons 26 and 27 [1,25(OH)2[26,27(n)-3H]D3] or on carbons 23 and 24 [1,25(OH)2[23,24(n)-3H]D3] reduced the in vivo metabolic clearance rate of 1,25(OH)2D3 by 36% and 37%, respectively, and reduced the in vitro renal catabolism of 1,25(OH)2D3 by 11% and 54%, respectively. Substitutions of 3H for 1H on carbons 23 and 24 as opposed to carbons 26 and 27 reduced conversion of [3H]1,25(OH)2D3 to [3H]1,24,25(OH)2D3 by 25% and to putative 24-oxo-1,23,25-dihydroxyvitamin D3 by 1600%. These results indicate that substitution of 3H for 1H on carbons 26 and 27 or on carbons 23 and 24 can reduce the metabolic clearance rate and in vitro metabolism of 1,25(OH)2D3 and quantitatively alter the pattern of metabolic products produced.
Halloran
B P
BP
Department of Medicine, University of California San Francisco 94121.
Bikle
D D
DD
Castro
M E
ME
Gee
E
E
D000818:Animals; D002117:Calcitriol / Q000378:metabolism* / Q000493:pharmacokinetics; D007553:Isotope Labeling; D007668:Kidney / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D011919:Rats, Inbred Strains; D014316:Tritium
D014316:Tritium; D002117:Calcitriol