Tanaka Y, Wichmann J K, Paaren H E, Schnoes H K, DeLuca H F
Proc Natl Acad Sci U S A. 1980 Nov;77(11):6411-4. doi: 10.1073/pnas.77.11.6411.
Labeled 25-hydroxyvitamin D3-26,23-lactone was isolated from the serum of vitamin D-repleted rats given [3 alpha-3H]-25-hydroxyvitamin D324 hr prior to sacrifice. The metabolite was identified by cochromatography with the authentic lactone on straight-phase and reversed-phase high-performance liquid chromatography. Production of the lactone was abolished by nephrectomy indicating that the kidney is the site of synthesis. Homogenate of kidneys from chickens given large doses of vitamin D can carry out in vitro production of the lactone from 25-hydroxyvitamin D3. When 1 alpha, 25-dihydroxyvitamin D3 was used as substrate, this system produced only traces of a compound believed to be 1 alpha, 25-dihydroxyvitamin D3-26,23-lactone. However, incubation of rachitic chicken kidney homogenates with 25-hydroxyvitamin D3-26,23-lactone produced substantial amounts of a compound that has been identified by mass spectrometry as 1 alpha, 25-dihydroxyvitamin D3-26,23-lactone. Thus, the development of a functional group on C-26 and eventual lactone formation takes place in kidney by a system acting on 25-hydroxyvitamin D3.
在处死前24小时给维生素D充足的大鼠注射[3α-³H]-25-羟基维生素D₃后，从其血清中分离出标记的25-羟基维生素D₃-26,23-内酯。通过与标准内酯在正相和反相高效液相色谱上共色谱法鉴定该代谢物。肾切除可消除内酯的产生，表明肾脏是合成部位。给大剂量维生素D的鸡的肾脏匀浆可在体外将25-羟基维生素D₃转化为内酯。当以1α,25-二羟基维生素D₃作为底物时，该系统仅产生痕量的一种化合物，据信该化合物为1α,25-二羟基维生素D₃-26,23-内酯。然而，用25-羟基维生素D₃-26,23-内酯孵育佝偻病鸡的肾脏匀浆可产生大量化合物，该化合物已通过质谱鉴定为1α,25-二羟基维生素D₃-26,23-内酯。因此，C-26上官能团的形成以及最终内酯的形成是在肾脏中通过作用于25-羟基维生素D₃的系统发生的。
