Henry H L, Fried S, Shen G Y, Barrack S A, Okamura W H
Department of Biochemistry, University of California, Riverside 92521.
J Steroid Biochem Mol Biol. 1991 Jun;38(6):775-9. doi: 10.1016/0960-0760(91)90091-i.
Three A-ring analogs of 1 alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3)--2-nor-1,3-seco-1,25(OH)2D3 (2-nor analog), 2-oxa-3-deoxy-25-OH-D3 (2-oxa analog), and A-homo-3-deoxy-3,3-dimethyl-2,4-dioxa-25-OH-D3 (A-homo analog)--were tested for their ability to inhibit 25-OH-D3-1 alpha-hydroxylase (1 alpha-hydroxylase) in isolated mitochondria and to alter 25-OH-D3 metabolism in cultured chick kidney cells. The 2-nor and 2-oxa analogs were relatively potent (Kis of 60 and 30 nM, respectively, compared with 170 nM for 1,25(OH)2D3), whereas the A-homo analog was completely ineffective in inhibiting 1 alpha-hydroxylase activity. In contrast, all three analogs were able to repress 1 alpha-hydroxylase and induce 24-hydroxylase activity in cultured chick kidney cells, suggesting that this process is not one of direct action in the mitochondria, but is more likely to be a receptor-mediated one.
对1α,25 - 二羟基维生素D3（1,25(OH)2D3）的三种A环类似物——2 - 去甲 - 1,3 - 开环 - 1,25(OH)2D3（2 - 去甲类似物）、2 - 氧杂 - 3 - 脱氧 - 25 - OH - D3（2 - 氧杂类似物）和A - 高 - 3 - 脱氧 - 3,3 - 二甲基 - 2,4 - 二氧杂 - 25 - OH - D3（A - 高类似物）——进行了测试，以考察它们抑制分离线粒体中25 - OH - D3 - 1α - 羟化酶（1α - 羟化酶）的能力以及改变培养的鸡肾细胞中25 - OH - D3代谢的能力。2 - 去甲和2 - 氧杂类似物相对强效（抑制常数分别为60和30 nM，相比之下，1,25(OH)2D3为170 nM），而A - 高类似物在抑制1α - 羟化酶活性方面完全无效。相反，所有三种类似物都能够在培养的鸡肾细胞中抑制1α - 羟化酶并诱导24 - 羟化酶活性，这表明该过程不是在线粒体中的直接作用过程，而更可能是受体介导的过程。
