Inhibitors of retinyl ester formation also prevent the biosynthesis of 11-cis-retinol.
Inhibitors of retinyl ester formation also prevent the biosynthesis of 11-cis-retinol.
复制标题
视黄酯形成的抑制剂也会阻止 11-顺式视黄醇的生物合成。
DOI：
10.1021/bi00454a001
复制
发表时间：
1990
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：
Trehan,A;Cañada,FJ;Rando,RR
摘要：视网膜色素上皮中的卵磷脂视黄醇酰基转移酶(LRAT)在微摩尔范围内可被维甲酸溴乙酸酯有效地抑制。这种抑制是竞争性的和可逆的。视黄基色素上皮还含有能够将添加的全反式视黄醇/M-视黄醇转化为11-m-视黄醇的酶活性。这种异构化很可能需要全反式TQ小酯的中间形成，而这些酯本身就是由LRAT作用产生的。通过研究AZZ-IRA/IS-视黄基-溴乙酸酯对异构化反应的影响，直接验证了这种可能性。当色素上皮膜与C/Z铁-视黄基-溴乙酸酯预孵育时，它们既不形成视黄酯，也不从添加的全反式视黄醇生成11-m-视黄醇。然而，如果首先允许色素上皮膜在加入全反式视黄醇之前形成全反式视黄酸酯，那么在没有抑制剂的情况下，11-m-视黄醇的形成速度接近于建立的速率。此外，11-m-视黄酸酯在这些条件下不会形成，从而排除了直接酯-酯异构化路线的可能性。因此，全反式视黄酸酯是生物合成11-间维A醇的必需中间体。
Revised Manuscript Received November 28, 1989 abstract: Lecithin retinol acyltransferase (LRAT) from the retinyl pigment epithelium is potently inhibited by-ínms-retinyl-bromoacetate inthe micromolar range. The inhibition is competitive and reversible. The retinyl pigment epithelium also contains an enzymatic activity capable of converting added all-ira/M-retinol into 11-m-retinol. This isomerization is likely to require the intermediateformation of all-trans-TQtiny\esters, which are themselves produced by LRAT action. Here this possibility is directly tested bystudying the effect of aZZ-ira/is-retinyl-bromoacetate on the isomerization reaction. When pigment epithelium membranes are preincubated with c/Z-irons-retinyl-bromoacetate, they form neither retinyl esters nor 11-m-retinol from added all-trans-retinol. However, if the pigment epithelium membranes are first allowed to form all-trans-retinyl esters from all-trans-retinol beforethe addition of all-trans-rzúny\-bromoacetate, then 11-m-retinol formation proceeds at close to the ratefound in the absence of inhibitor. In addition, 11-m-retinyl esters are not formed under these conditions, eliminating the possibility of a direct ester-ester isomerization route. Therefore, all-trans-retinyl esters are obligate intermediates in the biosynthesis of 11-m-retinol.