Isolation and identification of 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3, a new metabolite of 1,25-dihydroxyvitamin D3 produced in rat kidney.

Isolation and identification of 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3, a new metabolite of 1,25-dihydroxyvitamin D3 produced in rat kidney.
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大鼠肾脏产生的 1,25-二羟基维生素 D3 的新代谢物 1,23-二羟基-24,25,26,27-四去甲维生素 D3 的分离和鉴定。

DOI:
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发表时间:
1987
期刊:
影响因子:
2.9
通讯作者:
A. Norman
A. Norman
中科院分区:
生物学3区
文献类型:
--
作者:
G. Reddy;K. Tserng;B. R. Thomas;R. Dayal;A. Norman

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用1,25-二羟维生素D_3(4 × 10 ~(-6)M)灌流大鼠肾脏,在体外产生一种新的维生素D_3代谢产物。通过高效液相色谱法从肾灌注液的脂质提取物中分离纯化。通过紫外分光光度法、质谱法、化学衍生法、化学合成法等方法,确定了新的代谢产物为1,23-二羟基-24,25,26,27-四去甲维生素D3。沿着新代谢产物,还分离出了其他三种先前鉴别的代谢产物,即1,24,25-三羟基维生素D3、1,25-二羟基-24-氧代维生素D3和1,23,25-三羟基-24-氧代维生素D3。以1,23,25-三羟基-24-氧代维生素D3为底物时也形成了新的代谢产物。因此,新的代谢产物符合以下代谢途径:1,25-二羟基维生素D3-1,24(R),25-三羟基维生素D3-1,25-二羟基-24-氧代维生素D3-1,23,25-三羟基-24-氧代维生素D3-1,23-二羟基-24,25,26,27-四降维生素D3。此外,我们在肾脏灌注系统中使用1 α,25-二羟基[1 β-3 H]维生素D3,并证明1,23-二羟基-24,25,26,27-四降维生素D3是1,25-二羟基维生素D3的主要进一步代谢物,当肾脏用1,25-二羟基维生素D3(6 × 10(-10)M)灌注4小时时,在最终灌注液中循环。1,23-二羟基-24,25,26,27-四去甲维生素D3(C-3醇)的生物活性及其与1-羟基-23-羧基-24,25,26,27-四去甲维生素D3(骨化酸或C-23酸)的代谢关系尚不清楚,1-羟基-23-羧基-24,25,26,27-四去甲维生素D3是先前鉴定的1,25-二羟基维生素D3的另一种侧链裂解代谢产物,目前正在进行研究。
A new metabolite of vitamin D3 was produced in vitro by perfusing rat kidneys with 1,25-dihydroxyvitamin D3 (4 X 10(-6) M). It was isolated and purified from the lipid extract of the kidney perfusate by high-performance liquid chromatography. By means of ultraviolet absorption spectrophotometry, mass spectrometry, chemical derivatization, and chemical synthesis, the new metabolite was identified as 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3. Along with the new metabolite, three other previously identified metabolites, namely, 1,24,25-trihydroxyvitamin D3, 1,25-dihydroxy-24-oxovitamin D3, and 1,23,25-trihydroxy-24-oxovitamin D3, were also isolated. The new metabolite was also formed when 1,23,25-trihydroxy-24-oxovitamin D3 was used as the substrate. Thus, the new metabolite fits into the following metabolic pathway: 1,25-dihydroxyvitamin D3----1,24(R),25-trihydroxyvitamin D3----1,25-dihydroxy-24-oxovitamin D3----1,23,25-trihydroxy-24-oxovitamin D3----1,23-dihydroxy-24,25,26,27-tetranorvitamin D3. Further, we used 1 alpha,25-dihydroxy[1 beta-3H]vitamin D3 in the kidney perfusion system and demonstrated 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3 as the major further metabolite of 1,25-dihydroxyvitamin D3, circulating in the final perfusate when kidneys were perfused with 1,25-dihydroxyvitamin D3 (6 X 10(-10) M) for 4 h. The biological activity of 1,23-dihydroxy-24,25,26,27-tetranorvitamin D3 (C-3 alcohol) and its metabolic relationship to 1-hydroxy-23-carboxy-24,25,26,27-tetranorvitamin D3 (calcitroic acid or C-23 acid), the other previously identified side-chain cleavage metabolite of 1,25-dihydroxyvitamin D3, are unknown and are presently undergoing investigation.
DOI: --
发表时间: 1983
期刊: The Journal of biological chemistry
影响因子: --
作者:
Napoli,JL;Pramanik,BC;Royal,PM;Reinhardt,TA;Horst,RL
通讯作者: Horst,RL
维生素 D 代谢物 1,25-二羟基-24-氧代-维生素 D3 和 1,23,25-三羟基-24-氧代-维生素 D3 的生物活性评估。
DOI: 10.1016/0003-9861(83)90254-0
发表时间: 1983
影响因子: 3.9
作者:
Mayer,E;Bishop,JE;Ohnuma,N;Norman,AW
通讯作者: Norman,AW
23,25-二羟基-24-氧代维生素 D3:肾脏中产生的维生素 D3 的代谢产物。
DOI: 10.1021/bi00277a009
发表时间: 1983
期刊: Biochemistry
影响因子: 2.9
作者:
Mayer,E;Reddy,GS;Chandraratna,RA;Okamura,WH;Kruse,JR;Popjàk,G;Bishop,JE;Norman,AW
通讯作者: Norman,AW
1,25,26-三羟基维生素 D3:分离、鉴定和生物活性。
DOI: 10.1016/0003-9861(81)90169-7
发表时间: 1981
影响因子: 3.9
作者:
Tanaka,Y;Schnoes,HK;Smith,CM;DeLuca,HF
通讯作者: DeLuca,HF
1 Alpha-25,26-三羟基维生素 D3:维生素 D3 的体内和体外代谢物。
DOI: 10.1021/bi00524a050
发表时间: 1981
期刊: Biochemistry
影响因子: 2.9
作者:
Reinhardt,TA;Napoli,JL;Praminik,B;Littledike,ET;Beitz,DC;Partridge,JJ;Uskoković,MR;Horst,RL
通讯作者: Horst,RL