MOLECULAR MECHANISMS IN VISUAL PIGMENT REGENERATION

The photochemical bleaching of vertebrate rhodopsin results in the cis to trans isomerization of the 11-cis-retinal protonated Schiff base. Hydrolysis of the Schiff base leads to the formation of opsin and all-trans-retinal. In order for vision to proceed, the enzymatic trans to cis isomerization of a retinoid must occur. Since retinoids exist as alcohols, aldehydes, or esters in the eye, there are potentially nine different routes for isomerization. Moreover, 11-cis-retinoids are approximately 4 kcal/mol higher in energy than their all-trans isomers. Thus, not only must the isomerization route be defined, but an energy source must be identified to power this process. It was discovered that the energy is provided for in a minimally two-step process involving membrane phospholipids as the energy source. First, all-trans-retinol (vitamin A) is esterified in the retinal pigment epithelium by lecithin retinol acyl transferase to produce an all-trans-retinyl ester. Second, this ester is directly transformed into 11-cis-retinol by an isomerohydrolase enzyme, in a process that couples the negative free energy of hydrolysis of the acyl ester to the formation of the strained 11-cis-retinoid.