Law W C, Rando R R
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115.
Biochemistry. 1988 May 31;27(11):4147-52. doi: 10.1021/bi00411a037.
all-trans-Retinol (vitamin A) is processed by membranes from the pigment epithelium of the amphibian or bovine eye to form 11-cis-retinoids. When the isomerization reaction is performed with either [15(S)-3H,14C]-all-trans-retinol or [15(R)-3H,14C]-all-trans-retinol as substrate, the resultant 11-cis-retinals, formed by the in vitro enzymatic oxidation of the retinols, retain their 3H in the former case and lose it in the latter. The ocular all-trans- (pro-R specific) and 11-cis-retinol (pro-S specific) dehydrogenases operate with different stereochemistries with respect to the prochiral methylene hydroxyl centers of their substrates. Inversion of stereochemistry at the prochiral retinol centers was shown to accompany the isomerization process in both the amphibian and bovine systems. The 11-cis-retinol formed from [15(S)-3H,14C]-all-trans-retinol was chemically isomerized with I2 to produce [15(R)-3H,14C]-all-trans-retinol. The 11-cis-retinol formed from [15(R)-3H,14C]-all-trans-retinol was chemically isomerized with I2 to produce [15(S)-3H,14C]-all-trans-retinol. The stereochemistry at the prochiral center of retinol is not affected by the I2-catalyzed double-bond isomerization process and, hence, inversion of stereochemistry at C-15 must accompany isomerization. The same inverted stereochemistry was found with the associated retinyl palmitates. Possible mechanistic reasons for the observed inversion of stereochemistry during isomerization are discussed.
全反式视黄醇（维生素A）由两栖动物或牛眼色素上皮的膜进行加工，形成11-顺式视黄醛类物质。当以[15(S)-3H,14C]-全反式视黄醇或[15(R)-3H,14C]-全反式视黄醇为底物进行异构化反应时，视黄醇经体外酶促氧化形成的11-顺式视黄醛，在前一种情况下保留其3H，而在后一种情况下失去3H。眼部的全反式（前手性R特异性）和11-顺式视黄醇（前手性S特异性）脱氢酶，相对于其底物的前手性亚甲基羟基中心，以不同的立体化学方式起作用。在前手性视黄醇中心的立体化学反转，在两栖动物和牛的系统中均显示伴随着异构化过程。由[15(S)-3H,14C]-全反式视黄醇形成的11-顺式视黄醇用I2进行化学异构化，生成[15(R)-3H,14C]-全反式视黄醇。由[15(R)-3H,14C]-全反式视黄醇形成的11-顺式视黄醇用I2进行化学异构化，生成[15(S)-3H,14C]-全反式视黄醇。视黄醇前手性中心的立体化学不受I2催化的双键异构化过程影响，因此，C-15处的立体化学反转必定伴随着异构化。在相关的视黄醇棕榈酸酯中也发现了相同的反转立体化学。讨论了异构化过程中观察到的立体化学反转的可能机理原因。
