Tian X Q, Holick M F
Department of Medicine and Department of Physiology, Boston University Medical Center, Massachusetts 02118, USA.
J Biol Chem. 1995 Apr 14;270(15):8706-11. doi: 10.1074/jbc.270.15.8706.
To examine the effect of microenvironments on previtamin D3<==>vitamin D3 isomerization, we have conducted kinetic studies of the reaction in an aqueous solution of beta-cyclodextrin. Our results showed that at 5 degrees C, the forward (k1) and reverse (k2) rate constants for previtamin D3<==>vitamin D3 isomerization were increased by more than 40 and 600 times, respectively, compared with those in n-hexane (k1, 8.65 x 10(-6) versus 1.76 x 10(-7) s-1; k2, 8.48 x 10(-6) versus 1.40 x 10(-8) s-1), the fastest rate of this isomerization ever reported at this temperature. Thermodynamic studies revealed that the equilibrium constant of the reaction was significantly reduced by more than 12-fold when compared to that in n-hexane at 5 degrees C, and the percentage of vitamin D3 at equilibrium was increased as the temperature was increased in beta-cyclodextrin. When complexed with beta-cyclodextrin, the previtamin D3<==>vitamin D3 isomerization became endothermic (delta H zero = 13.05 kJ mol-1) in contrast to being exothermic in other media. We propose that thermodynamically unfavorable cZc conformers of previtamin D3 are stabilized by beta-cyclodextrin, and thus the rate of the isomerization is increased. This conformation-controlled process may play an important role in the modulation of previtamin D3<==>vitamin D3 endocrine system in vivo such as in the sea urchin.
为研究微环境对维生素原D3⇌维生素D3异构化的影响，我们进行了该反应在β-环糊精水溶液中的动力学研究。我们的结果表明，在5℃时，与在正己烷中相比，维生素原D3⇌维生素D3异构化的正向（k1）和反向（k2）速率常数分别增加了40倍和600倍以上（k1：8.65×10⁻⁶对1.76×10⁻⁷ s⁻¹；k2：8.48×10⁻⁶对1.40×10⁻⁸ s⁻¹），这是该温度下报道的该异构化的最快速率。热力学研究表明，与5℃时正己烷中的反应相比，该反应的平衡常数显著降低了12倍以上，并且在β-环糊精中，随着温度升高，平衡时维生素D3的百分比增加。与β-环糊精络合时，维生素原D3⇌维生素D3异构化变为吸热反应（ΔH⁰ = 13.05 kJ mol⁻¹），而在其他介质中为放热反应。我们提出，维生素原D3热力学上不利的cZc构象异构体被β-环糊精稳定，因此异构化速率增加。这种构象控制过程可能在体内对维生素原D3⇌维生素D3内分泌系统的调节中起重要作用，例如在海胆中。
