INVIVO ISOMERIZATION OF ALL-TRANS-RETINOIDS TO 11-CIS-RETINOIDS IN THE EYE OCCURS AT THE ALCOHOL OXIDATION-STATE
INVIVO ISOMERIZATION OF ALL-TRANS-RETINOIDS TO 11-CIS-RETINOIDS IN THE EYE OCCURS AT THE ALCOHOL OXIDATION-STATE
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DOI：
10.1021/bi00369a020
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发表时间：
1986-10-21
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：
BERNSTEIN, PS;RANDO, RR
漂白后活眼视色素再生的脊椎动物生化途径在很大程度上是未知的。由于全反式类维生素A异构化为11-顺式类维生素A可以通过维生素A的醛、醇或酯形式发生，因此确定体内异构化的类维生素A的氧化态很重要。为了解决这个问题，光适应大鼠和青蛙腹腔注射[15- 3 H]-全反式视黄醇和[15- 14 C]-全反式视黄醇的混合物。在4或24小时的暗适应后，分析动物眼中的标记类维生素A。所有大鼠在11-顺式-视黄醛中预期3 H标记（相对于14 C）损失50%，当[15- 3 H]视黄醇氧化为视黄醛时必然发生3 H损失。大鼠眼睛中的11-顺式-视黄酯在4 h时保留了67%的3 H标记，当大鼠用4-甲基吡唑（一种已知抑制暗适应的醇脱氢酶抑制剂）预处理时，这一比例可增加至81%。该结果表明，在大鼠眼中，类维生素A异构化发生在醇氧化态。如果它发生在醛的氧化态，至少有50%的3 H在11-顺式视黄酯会失去。通过观察发现，与对照大鼠相比，暗适应大鼠（其乙醇脱氢酶已被4-甲基吡唑抑制）眼中11-顺式视黄酯的量增加，强调了该异构化途径的重要性，该结果仅在类维生素A在体内以乙醇氧化态异构化时才可理解。当在青蛙身上进行同样的实验时，观察到所有类维生素A中3 H标记的意外大量损失，阻止了该动物中类维生素A异构化氧化态的明确证明。然而，值得注意的是，在注射标记的全反式视黄醇后4小时，在蛙眼中首先大量形成的11-顺式类维生素A是11-顺式视黄醇。这一结果表明，青蛙，像大鼠一样，可能会产生11-顺式维甲酸异构化的醇氧化态。
The vertebrate biochemical pathway for regeneration of visual pigments in the living eye after bleaching is largely uncharacterized. Since isomerization of an all-trans-retinoid to an 11-cis-retinoid could conceivably occur via the aldehyde, alcohol, or ester forms of vitamin A, it is important to determine the oxidation state of the retinoid that is isomerized in vivo. To address this problem, light-adapted rats and frogs were injected intraperitoneally with a mixture of [15-3H]-all-trans-retinol and [15-14C]-all-trans-retinol. After 4 or 24 h of dark adaptation, labeled retinoids in the animal''s eyes were analyzed. All rats had the expected 50% loss of 3H label (relative to 14C) in 11-cis-retinal, a loss of 3H that must occur when [15-3H]retinol is oxidized to retinal. 11-cis-Retinyl esters in the rats'' eyes at 4 h retained 67% of the 3H label, and this could be increased to 81% when the rats were pretreated with 4-methylpyrazole, an alcohol dehydrogenase inhibitor known to inhibit dark adaptation. This result demonstrates that retinoid isomerization occurs at the alcohol oxidation state in the rat eye. Had it occurred at the aldehyde oxidation state, at least 50% of the 3H in the 11-cis-retinyl esters would have been lost. The importance of this isomerization pathway is emphasized by the observation that dark-adapting rats whose alcohol dehydrogenase(s) had been inhibited by 4-methylpyrazole had increased amounts of 11-cis-retinyl ester in their eyes relative to control rat eyes, a result that is understandable only if retinoids are isomerized in vivo at the alcohol oxidation state. When these same experiments were performed on frogs, an unexpectedly large loss of 3H label in all retinoids was observed, preventing a definite demonstration of the oxidation state of retinoid isomerization in this animal. It was noted, howebver, that 4 h after injection with labeled all-trans-retinol the first 11-cis-retinoid formed in substantial amounts in the frog eye was 11-cis-retinol. This result indicates that frogs, like rats, may produce 11-cis-retinoids by isomerization at the alcohol oxidation state.