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Metabolic pathways from 1 alpha,25-dihydroxyvitamin D3 to 1 alpha,25-dihydroxyvitamin D3-26,23-lactone. Stereo-retained and stereo-selective lactonization.

1987; Elsevier BV; Volume: 262; Issue: 15 Linguagem: Inglês

10.1016/s0021-9258(18)48219-1

1083-351X

Seiichi Ishizuka, Anthony W. Norman,

Growth Hormone and Insulin-like Growth Factors

The present study was carried out in order to elucidate the metabolic pathway from la,25-(OH)2D3 to la,25-(OH)2D3-26,23-lactone.For that purpose, we stereospecifically synthesized the vitamin D3 derivatives la,23(S),25-(OH)3D3, la,23(S),25(R),26-tetra-hydroxyvitaminD3, and 23(S),25(R)-la,25-dihydroxyvitamin D3-lactol.The in vitro metabolism of these compounds was examined in kidney homogenates and intestinal mucosa homogenates from la,25-(OH)zD3supplemented chicks.The naturally occurring 23(S),25(R)-la,25-dihydroxyvitamin D3-26,23-lactone was produced (in increasing amounts) from la,25-(OH)2D3, la,25(R),26-(OH)sD3, la,23(S),%-(OH)&, 1~~,23(S),25(R),26-(OH)~D~, and 23(S),25(R)-la,25-(OH)2D3-26,23-lactol.These results indicated that there are two possible metabolic pathways from la,25-(OH)& to ia,23(S),25(R),26-(OH),D3: the major one is by way of ~Y , Z ~( S ) , ~~-( O H ) ~D ~ and the minor one is by way of la,25(R),26-(OH)3D3. 10,23(S),25(R),26-Tetrahydroxyvitamin D3 is further metabolized to 23(S),25(R)-la,25-dihydroxyvitamin D3-26,23-lactone via 23(S),25(R)-la,25-dihydroxyvitamin D3-26,23-lactol.In the course of our studies, a new biosynthetic vitamin D3 metabolite was isolated in pure form.This metabolite was identified as 23(S),25(R)-la,25-(OH)2D3-26,23-lactol by UV spectrophotometry and mass spectrometry.Furthermore, we establish in this report that the lactonization of 1(~,23,25,26-(OH)~D~ and la,25-(OH)2D3-26,23-lactol occurs in a stereo-retained and stereo-selective fashion.ln,25-Dihydroxyvitamin D3-26,23-lactone (1a,25-(OH),D3-26,23-lactone)' is a major metabolite of la,25-dihydroxyvitamin D3 (1~r,%-(oH)~D,), recently isolated and chemically characterized from the plasma of rats and dogs given phar-* The costs of publication of this article were defrayed in part by the payment of page charges.