4.8 Article

Highly efficient retinal metabolism in cones

Publisher

NATL ACAD SCIENCES
DOI: 10.1073/pnas.0806593105

Keywords

11-cis retinal; 11-cis retinol; all-trans retinal; retinol dehydrogenase; visual cycle

Funding

  1. Japan Society for the Promotion of Science [20370060, 20700350]
  2. Human Frontier Science Program
  3. Naito Foundation
  4. Grants-in-Aid for Scientific Research [20370060, 20700350] Funding Source: KAKEN

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After bleaching of visual pigment in vertebrate photoreceptors, all-trans retinal is reduced to all-trans retinol by retinol dehydrogenases (RDHs). We investigated this reaction in purified carp rods and cones, and we found that the reducing activity toward all-trans retinal in the outer segment (OS) of cones is > 30 times higher than that of rods. The high activity of RDHs was attributed to high content of RDH8 in cones. In the inner segment (IS) in both rods and cones, RDH8L2 and RDH13 were found to be the major enzymes among RDH family proteins. We further found a previously undescribed and effective pathway to convert 11-cis retinol to 11-cis retinal in cones: this oxidative conversion did not require NADP(+) and instead was coupled with reduction of all-trans retinal to all-trans retinol. The activity was > 50 times effective than the oxidizing activity of RDHs that require NADP(+). These highly effective reactions of removal of all-trans retinal by RDH8 and production of 11-cis retinal by the coupling reaction are probably the underlying mechanisms that ensure effective visual pigment regeneration in cones that function under much brighter light conditions than rods.

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