Isomerization of all-trans-retinoic acid to 9-cis-retinoic acid.
Isomerization of all-trans-retinoic acid to 9-cis-retinoic acid.
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DOI：
10.1042/bj2990459
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发表时间：
1994-04
期刊：
影响因子：
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通讯作者：
Jonathan M. Urbach;R. Rando
中科院分区：
文献类型：
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作者：
Jonathan M. Urbach;R. Rando
9-顺式维甲酸生物活性的发现对其生物合成方式提出了疑问。一个简单的机制涉及全反式维甲酸直接异构化为9-顺式维甲酸。这表明，牛肝膜，而不是上清馏分，可以异构化全反式维甲酸为9-顺式维甲酸和13-顺式维甲酸。生成的9-顺式维甲酸的浓度接近平衡浓度，这里确定的平衡浓度约为15%。然而，异构化过程不能被证明是饱和的，并且在测量的浓度范围内（8.3 nM至3微米），在全反式维甲酸中是一级的。用牛肝微粒体测量的异构化反应似乎是由巯基介导的，因为它们可以被特定的巯基阻断试剂如n -乙基马来酰亚胺阻断。有趣的是，这里观察到的非立体特异性行为与全反式维甲酸应用于细胞时观察到的行为相似。最后，当与肝微粒体和全反式视黄醇或全反式视网膜进行反应时，没有发现明显的9-顺式类维甲酸形成。
The discovery of the biological activity of 9-cis-retinoic acid raises questions as to its mode of biosynthesis. A simple mechanism involves the direct isomerization of all-trans-retinoic acid to 9-cis-retinoic acid. It is shown here that bovine liver membranes, but not supernatant fractions, can isomerize all-trans-retinoic acid into 9-cis-retinoic acid and 13-cis-retinoic acid. The concentration of 9-cis-retinoic acid generated approaches its equilibrium concentration, which is determined here to be approximately 15%. However, the isomerization process could not be shown to be saturable, and is first-order in all-trans-retinoic acid in the concentration range measured (8.3 nM to 3 microM). Isomerization reactions measured using bovine liver microsomes appear to be mediated by thiol groups, as they can be blocked by group-specific thiol-blocking reagents such as N-ethylmaleimide. It is interesting to note that the non-stereospecific behaviour observed here mimics what is observed when all-trans-retinoic acid is applied to cells. Finally, significant formation of 9-cis-retinoids was not found when the reaction was carried out with liver microsomes and either all-trans-retinol or all-trans-retinal.