Calcitroic acid, end product of renal metabolism of 1,25-dihydroxyvitamin D3 through the C-24 oxidation pathway

Biochemistry ◽  
1989 ◽  
Vol 28 (4) ◽  
pp. 1763-1769 ◽  
Author(s):  
G. Satyanarayana Reddy ◽  
Kou Yi Tserng
Keyword(s):  
Renal Metabolism ◽  
Dihydroxyvitamin D3 ◽  
Oxidation Pathway ◽  
1,25 Dihydroxyvitamin D3

1,25-Dihydroxyvitamin D3-inducible catabolism of vitamin D metabolites in mouse intestine

1990 ◽  
Vol 258 (4) ◽  
pp. G557-G563 ◽  
Author(s):  
M. Tomon ◽  
H. S. Tenenhouse ◽  
G. Jones
Keyword(s):  
Vitamin D ◽  
Enzyme Activity ◽  
Actinomycin D ◽  
Vitamin D Metabolites ◽  
Catabolic Pathway ◽  
Dihydroxyvitamin D3 ◽  
Oxidation Pathway ◽  
1,25 Dihydroxyvitamin D3 ◽  
Mouse Intestine ◽  
Alpha Amanitin

The 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]-inducible C-24 oxidation pathway is a major catabolic pathway for vitamin D metabolites in target tissues. Using intestinal homogenates derived from 1,25(OH)2D3-treated mice, we examined the time course of induction, the intestinal localization and kinetics of induced enzyme activity, as well as the sensitivity of induction to transcriptional inhibitors actinomycin D and alpha-amanitin. 24-Hydroxylation of 500 nM 3H-labeled 25-hydroxyvitamin D3 [25(OH)D3] and 50 nM 3H-labeled 1,25(OH)2D3 by duodenal homogenates was detected 1 h after 1,25(OH)2D3 treatment; C-24 oxidation products of 25(OH)D3 and 1,25(OH)2D3 peaked at approximately 6 h and remained elevated for 17 h. Induced enzyme activity was localized to the mitochondrial fraction, was highest in duodenum, and was also detected in jejunum, ileum, and colon. The apparent Michaelis constant of the induced duodenal enzyme for 25(OH)D3 was 451 nM and for 1,25(OH)2D3 was 14 nM. Induction of intestinal catabolic activity was inhibited by prior treatment of 1,25(OH)2D3-injected mice with either actinomycin D or alpha-amanitin. The characteristics of the 1,25(OH)2D3-inducible C-24 oxidation pathway in the intestine resembled that of the kidney. However, the catabolic pathway was constitutively expressed only in the kidney. We conclude that 1,25(OH)2D3-inducible degradation of vitamin D metabolites occurs throughout the length of mouse intestine and can be prevented by transcriptional inhibitors, suggesting that mRNA synthesis is required for the induction process.

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

1989 ◽  
Vol 262 (1) ◽  
pp. 173-180 ◽  
Author(s):  
G Makin ◽  
D Lohnes ◽  
V Byford ◽  
R Ray ◽  
G Jones
Keyword(s):  
Bone Cells ◽  
Cell Metabolism ◽  
Osteoblastic Cell ◽  
Target Cells ◽  
Dihydroxyvitamin D3 ◽  
Osteoblastic Cell Line ◽  
Oxidation Pathway ◽  
1,25 Dihydroxyvitamin D3 ◽  
Rapid Clearance ◽  
Umr 106

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.

The renal metabolism of 25-hydroxyvitamin D3 in the rat: Regulation by 1,25-dihydroxyvitamin D3

1983 ◽  
Vol 35 (1) ◽  
pp. 438-442 ◽  
Author(s):  
Russell T. Turner ◽  
Norman H. Bell ◽  
David J. Baylink
Keyword(s):  
Renal Metabolism ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3
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