Chemistry of the Retinoid (Visual) Cycle

Photocyclic behavior of rhodopsin induced by an atypical isomerization mechanism

“…Furthermore, this 11,13-dicis-bound photoproduct is stable to Schiff base hydrolysis, and can thermally revert back to its inactive 11-cis form. Notably, the Rh6mr-specific photocycle is similar to those of microbial Rhs, such as bacterio-Rh, in which exposure to light isomerizes the all-trans-retinal chromophore to the 13-cis form that thermally reisomerizes back to the all-trans form (6)(7)(8). Thus, an isomerization around the C 13 =C 14 double bond rather than the C 11 =C 12 position plays a critical role in achieving an active Meta-II-like helical opening in Rh6mr.…”

“…All classes of Rhs feature a heptahelical transmembrane structure that incorporates a covalently bound retinal chromophore, but they differ in their ability to interconvert between their two spectral absorption states driven by light exposure (2). Although vertebrate Rh undergoes a one-way photobleaching reaction of the retinal chromophore after light absorption (8), microbial Rhs exhibit an intrinsic photocyclic behavior with no chromophore release (2,8). This makes vertebrate Rhs unsuitable for optogenetic applications that require reversible control over effector ligands.…”

“…This makes vertebrate Rhs unsuitable for optogenetic applications that require reversible control over effector ligands. Nevertheless, all Rhs require a cis-trans/trans-cis isomerization of their chromophores to trigger a protein conformational change that mediates the downstream signaling cascade or energy conversion (2,8). Previous studies on bovine Rh regenerated with sixcarbon-ring retinal chromophores (Rh6mr) featuring a locked C 11 =C 12 cis-trans isomerization (SI Appendix, Fig.…”

Two-photon microscopy reveals early rod photoreceptor cell damage in light-exposed mutant mice

“…4). Retinoids are highly reactive compounds prone to oxidation, isomerization, fragmentation, and condensation both with themselves and other membrane and protein components (60,61). atRAL along with its derivative products likely are the initiators of photoreceptor cell pathology for several reasons: (i) phototransduction is the only light-sensitive pathway in ROS and this process involves the conversion of retinoids and generation of atRAL (62,63); (ii) such light-induced degeneration can be prevented by pretreatment with retinoid cycle inhibitors (Fig.…”

Conditional Ablation of Retinol Dehydrogenase 10 in the Retinal Pigmented Epithelium Causes Delayed Dark Adaption in Mice

“…To maintain vision, the photo-activated chromophore, all-trans-retinal, is isomerized back to the photo-sensitive form, 11-cis-retinal, via the visual (retinoid) cycle (3). All-transretinal is first reduced to all-trans-retinol by enzymes of the short-chain dehydrogenase (SDR) 2 family, retinol dehydrogenase 12 (RDH12) and RDH8, present in the inner and outer segments of the retina, respectively (4,5). All-trans-retinol is transported to the retinal pigmented epithelium (RPE), where it is sequentially esterified by lecithin retinol acyltransferase (LRAT) to all-trans-retinyl ester (6).…”