Jones G, Edwards N, Vriezen D, Porteous C, Trafford D J, Cunningham J, Makin H L
Department of Biochemistry, Queen's University, Kingston, Ontario, Canada.
Biochemistry. 1988 Sep 6;27(18):7070-9. doi: 10.1021/bi00418a060.
The in vivo metabolism of dihydrotachysterol3, an analogue of vitamin D3 and a potent calcemic factor, has been studied in the rat. This in vivo metabolism is compared to the in vitro metabolism of 25-hydroxydihydrotachysterol3 in the perfused rat kidney. Using mass spectrometry and ultraviolet spectroscopy, we have identified seven novel metabolites derived from 25-hydroxydihydrotachysterol3. The seven compounds represent intermediates on two renal pathways (24-oxidation and 26,23-lactone formation) also observed for 25-hydroxyvitamin D3. No evidence was found for the renal synthesis of a 1-hydroxylated metabolite of 25-hydroxydihydrotachysterol3 analogous to the hormone 1,25-dihydroxyvitamin D3. Two of the compounds formed in vitro, 24,25-dihydroxydihydrotachysterol3 and 25-hydroxydihydrotachysterol 26,23-lactone, were also formed in vivo. In vivo studies also revealed the formation of two other unidentified metabolites which are presumed to be formed nonrenally and may be calcemic factors. This work shows that dihydrotachysterol3 metabolism is complex and probably utilizes the same side-chain enzymes as vitamin D3. In addition, our work also confirms that intermediates postulated to lie on pathways to 26,23-lactone in the vitamin D3 series are also formed for the side chain in dihydrotachysterol3.
维生素D3的类似物及强效血钙因子二氢速甾醇3在大鼠体内的代谢已得到研究。这种体内代谢与25-羟基二氢速甾醇3在灌注大鼠肾脏中的体外代谢进行了比较。利用质谱和紫外光谱，我们鉴定出了7种源自25-羟基二氢速甾醇3的新代谢物。这7种化合物代表了25-羟基维生素D3也具有的两条肾脏代谢途径（24-氧化和26,23-内酯形成）的中间产物。未发现肾脏合成与激素1,25-二羟基维生素D3类似的25-羟基二氢速甾醇3的1-羟基化代谢物的证据。体外形成的两种化合物，24,25-二羟基二氢速甾醇3和25-羟基二氢速甾醇26,23-内酯，在体内也有形成。体内研究还揭示了另外两种未鉴定代谢物的形成，推测它们是在肾脏外形成的，可能是血钙因子。这项工作表明二氢速甾醇3的代谢很复杂，可能利用了与维生素D3相同的侧链酶。此外，我们的工作还证实，维生素D3系列中推测存在于通往26,23-内酯途径上的中间产物在二氢速甾醇3的侧链中也会形成。
