Regulation of 25-hydroxyvitamin D3-1-hydroxylase in vivo.
Regulation of 25-hydroxyvitamin D3-1-hydroxylase in vivo.
复制标题
体内 25-羟基维生素 D3-1-羟化酶的调节。
DOI：
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发表时间：
1974
影响因子：
4.8
通讯作者：
A. Norman
中科院分区：
文献类型：
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作者：
H. Henry;R. Midgett;A. Norman
摘要：阐明肾脏产生1,25-二羟基胆钙化醇（1,25-(OH)2D3）的因素对理解钙稳态至关重要。在饮食维生素D、钙和磷改变或甲状旁腺切除术后，使用测量初始反应速率的酶测定法跟踪肾脏25- oh -胆钙化醇-1-羟化酶（1-羟化酶）比活性的变化。1-羟化酶比活性随膳食维生素D含量的变化而变化5- 20倍；通过给予维生素D3（每天1.6 nmol）或给予1,25-二羟维生素D3（每天0.52 nmol），它的比活性降低到每毫克蛋白质每分钟0.1至0.6摩尔，并且在停止类固醇后，它显着增加到每毫克蛋白质每分钟0.7至1.8摩尔的水平。这些变化不依赖于血清钙的可测量变化，并且与饮食中的钙和磷水平无关。酶活性降至维生素d充足雏鸡的特征值所需的时间与维生素D3剂量的大小成反比（7天，每天3.2 nmol； 2天，每天32.5 nmol）。在维生素D3持续存在的情况下，1-羟化酶活性被调节在一个更窄的范围内（每毫克蛋白质每分钟0.1至0.6摩尔），酶水平反映了饮食中钙的可用性。膳食钙的变化与血清钙的变化平行。1-羟化酶活性与血清Ca2+水平呈极显著负相关（p < 0.001）。酶活性与血清磷和肾无机磷水平无显著相关性。切除甲状旁腺后，在24小时内，1-羟化酶活性降低到维生素d处理的鸡的水平（每毫克蛋白质0.2至0.04 pmol / min）。这表明甲状旁腺激素状态与钙化醇状态在决定1-羟化酶特异性活性方面同样重要。通过测定环己亚胺处理后的酶活性，测定胆钙化醇缺乏和补充雏鸡体内1-羟化酶的半衰期、合成和降解速率（Berlin, c.m ., and Schimke， R. T. (1965) Mol. Pharmacol. 1,149）。维生素D状态对半衰期或降解率没有影响（t1/2 = 4至5小时）；缺乏维生素d的鸟类的合成速度是补充维生素d的鸟类的4.7倍。总之，调节25- oh - d3 -1-羟化酶稳态水平的两个主要成分（维生素D状态和血清甲状旁腺钙激素）似乎是通过改变该酶的生物合成速率来发挥作用的。
Abstract The elucidation of the factors which govern the production by the kidney of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) is essential to an understanding of calcium homeostasis. Changes in the specific activity of the renal 25-OH-cholecalciferol-1-hydroxylase (1-hydroxylase) were followed after alterations in dietary vitamin D, calcium, and phosphorus or parathyroidectomy using an enzyme assay which measures initial reaction rates. 1-Hydroxylase specific activity varied over a 5- to 20-fold range with changes in dietary vitamin D; it was decreased to a specific activity of 0.1 to 0.6 pmole per min per mg of protein by administration of vitamin D3 (1.6 nmoles per day) or equally effectively by administration of 1,25-dihydroxyvitamin D3 (0.52 nmole per day), and it increased markedly to a level of 0.7 to 1.8 pmoles per min per mg of protein upon withdrawal of the steroids. These changes were not dependent upon measurable changes in serum calcium and occurred regardless of dietary calcium and phosphorous levels. The time period required for the enzyme activity to fall to values characteristic of a vitamin D-repleted chick was inversely proportional to the magnitude of the dose of vitamin D3 given (7 days with 3.2 nmoles per day; 2 days with 32.5 nmoles per day). In the continued presence of vitamin D3, the 1-hydroxylase activity is modulated over a more narrow range (0.1 to 0.6 pmole per min per mg of protein) and enzyme levels reflect the dietary availability of calcium. Changes in dietary calcium were reflected by parallel changes in serum calcium. There was a highly significant (p l 0.001) inverse correlation between 1-hydroxylase activity and serum Ca2+ levels. No significant correlations were found between the enzyme activity and serum phosphorous or renal inorganic phosphorous levels. Parathyroidectomy of cholecalciferol-depleted chicks resulted in a decrease, in 24 hours, of 1-hydroxylase activity to levels characteristic of vitamin D-treated chicks (0.2 to 0.04 pmoles per min per mg of protein). This suggests that parathyroid hormone status is equally as important as calciferol status in determining 1-hydroxylase specific activity. The half-life and rates of synthesis and degradation of 1-hydroxylase in cholecalciferol-deficient and -repleted chicks were determined by measuring enzyme activity following cycloheximide treatment (Berlin, C. M., and Schimke, R. T. (1965) Mol. Pharmacol. 1, 149). Vitamin D status had no effect on the half-life or degradation rate (t1/2 = 4 to 5 hours); the rate of synthesis in deficient birds is 4.7 times that in vitamin D-repleted birds. In summary, the two major components which regulate the steady state level of 25-OH-D3-1-hydroxylase (vitamin D status and serum calcium-parathyroid hormone) appear to exert their effect by changes in the rate of the biosynthesis of this enzyme.