Regulation of isomerohydrolase activity in the visual cycle.
Regulation of isomerohydrolase activity in the visual cycle.
复制标题
视觉周期中异构水解酶活性的调节。
DOI：
10.1021/bi971908d
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发表时间：
1998
期刊：
影响因子：
2.9
通讯作者：
Rando,RR
中科院分区：
文献类型：
--
作者：
Winston,A;Rando,RR
虽然在视觉周期中从全反式类维甲酸到11顺式类维甲酸的整个生物合成途径是已知的，但对于哪一步可能是限速的以及如何进行控制却知之甚少。一个可能的控制目标是异构体水解酶，它将所有反式视黄醇酯加工成11-顺式视黄醇。利用牛视网膜色素上皮膜，由全反式视黄醇酯合成11-顺式视黄醇的基础速率极慢[3.5 pmol 11-顺式视黄醇min-1（mg蛋白）-1]，只形成少量的11-顺式视黄醇酯。然而，视黄醇结合蛋白的加入刺激11-顺式视黄醇形成的因子约为13。特异性蛋白-蛋白相互作用可能不重要，因为牛血清白蛋白和生理相关的细胞视黄醛结合蛋白（CRALBP）都在相同程度上刺激11-顺式视黄醇的形成，尽管CRALBP的浓度要低得多。在结合蛋白存在的情况下，相对较快的异构化速率[44.3 pmol 11-顺式视黄醇min-1（mg蛋白）-1]表明，视觉循环中的限速酶不一定是异构水解酶。此外，11-顺式视黄醇被证明可以抑制异构体水解酶，为调节视觉周期和结合蛋白的刺激作用提供了一种简单的机制。
While the overall biosynthetic pathway leading fromall-trans-retinoids to 11-cis-retinoids in the visual cycle is understood, little is known about which step(s) may be rate-limiting and how control is exerted. One possible target for control is the isomerohydrolase, which processesall-trans-retinyl esters into 11-cis-retinol. The basal rate of 11-cis-retinol synthesis fromall-trans-retinyl esters is extremely slow using bovine retinal pigment epithelial membranes [3.5 pmol of 11-cis-retinol min-1(mg of protein)-1], and only small amounts of 11-cis-retinyl ester are formed. However, the addition of retinol binding proteins stimulates 11-cis-retinol formation by a factor of approximately 13. Specific protein−protein interactions are probably unimportant because bovine serum albumin and the physiologically relevant cellular retinaldehyde binding protein (CRALBP) both stimulate 11-cis-retinol formation to the same extent, although CRALBP does so at much lower concentrations. The relatively rapid rate of isomerization in the presence of binding proteins [44.3 pmol of 11-cis-retinol min-1(mg of protein)-1] suggests that the rate-limiting enzyme in the visual cycle need not be the isomerohydrolase. Also, 11-cis-retinol is shown to inhibit isomerohydrolase, providing a simple mechanism for regulation of the visual cycle and the stimulating effect of binding proteins.