Vitamin A aldehyde-taurine adduct and the visual cycle.

Abstract

Visual pigment consists of opsin covalently linked to the vitamin A-derived chromophore, 11-<i>cis</i>-retinaldehyde. Photon absorption causes the chromophore to isomerize from the 11-<i>cis-</i> to all-<i>trans</i>-retinal configuration. Continued light sensitivity necessitates the regeneration of 11-<i>cis</i>-retinal via a series of enzyme-catalyzed steps within the visual cycle. During this process, vitamin A aldehyde is shepherded within photoreceptors and retinal pigment epithelial cells to facilitate retinoid trafficking, to prevent nonspecific reactivity, and to conserve the 11-<i>cis</i> configuration. Here we show that redundancy in this system is provided by a protonated Schiff base adduct of retinaldehyde and taurine (A1-taurine, A1T) that forms reversibly by nonenzymatic reaction. A1T was present as 9-<i>cis</i>, 11-<i>cis</i>, 13-<i>cis</i>, and all-<i>trans</i> isomers, and the total levels were higher in neural retina than in retinal pigment epithelium (RPE). A1T was also more abundant under conditions in which 11-<i>cis</i>-retinaldehyde was higher; this included black versus albino mice, dark-adapted versus light-adapted mice, and mice carrying the Rpe65-Leu450 versus Rpe65-450Met variant. Taurine levels paralleled these differences in A1T. Moreover, A1T was substantially reduced in mice deficient in the Rpe65 isomerase and in mice deficient in cellular retinaldehyde-binding protein; in these models the production of 11-<i>cis</i>-retinal is compromised. A1T is an amphiphilic small molecule that may represent a mechanism for escorting retinaldehyde. The transient Schiff base conjugate that the primary amine of taurine forms with retinaldehyde would readily hydrolyze to release the retinoid and thus may embody a pool of 11-<i>cis</i>-retinal that can be marshalled in photoreceptor cells.