Retinol dehydrogenases (RDHs) in the visual cycle.
The isomerization of 11-cis retinal to all-trans retinal in photoreceptors is the first step in vision. For photoreceptors to function in constant light, the all-trans retinal must be converted back to 11-cis retinal via the enzymatic steps of the visual cycle. Within this cycle, all-trans retinal is reduced to all-trans retinol in photoreceptors and transported to the retinal pigment epithelium (RPE). In the RPE, all-trans retinol is converted to 11-cis retinol, and in the final enzymatic step, 11-cis retinol is oxidized to 11-cis retinal. The first and last steps of the classical visual cycle are reduction and oxidation reactions, respectively, that utilize retinol dehydrogenase (RDH) enzymes. The visual cycle RDHs have been extensively studied, but because multiple RDHs are capable of catalyzing each step, the exact RDHs responsible for each reaction remain unknown. Within rods, RDH8 is largely responsible for the reduction of all-trans retinal with possible assistance from RDH12. retSDR1 is thought to reduce all-trans retinal in cones. In the RPE, the oxidation of 11-cis retinol is carried out by RDH5 with possible help from RDH11 and RDH10. Here, we review the characteristics of each RDH in vitro and the findings from knockout models that suggest the roles for each in the visual cycle.
Parker
Ryan O
RO
Department of Ophthalmology, Medical University of South Carolina, 167 Ashley Avenue Charleston, SC 29403, United States. parkerry@musc.edu
Crouch
Rosalie K
RK
D000818:Animals; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D012160:Retina / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000502:physiology*; D055213:Retinal Pigment Epithelium / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*
D050697:Retinal Dehydrogenase
Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4404-9
9539749
J Biol Chem. 1995 Jan 20;270(3):1107-12
7836368
Nat Genet. 2004 Aug;36(8):850-4
15258582
J Biol Chem. 2001 Aug 31;276(35):32456-65
11418621
Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19565-70
18048336
Invest Ophthalmol Vis Sci. 2007 Feb;48(2):534-42
17251447
Biochemistry. 2003 Dec 23;42(50):14838-45
14674758
J Biol Chem. 2008 Jul 18;283(29):20299-308
18502750
J Biol Chem. 2000 Apr 14;275(15):11034-43
10753906
J Biol Chem. 2006 Dec 8;281(49):37697-704
17032653
J Biol Chem. 2005 Mar 11;280(10):8694-704
15634683
Mol Cell Biol. 2007 Feb;27(4):1370-9
17130236
J Biol Chem. 2000 Sep 8;275(36):28128-38
10871622
J Biol Chem. 2003 Aug 22;278(34):32380-9
12807874
Exp Eye Res. 2008 Feb;86(2):344-54
18163989
Invest Ophthalmol Vis Sci. 2009 Nov;50(11):5089-97
19458327
Mol Cell Biol. 2000 Jun;20(12):4275-87
10825191
J Biol Chem. 2002 Nov 22;277(47):45537-45546
12226107
Nat Neurosci. 2009 Mar;12(3):295-302
19182795
J Biol Chem. 2002 Aug 9;277(32):28909-15
12036956
Mol Cell Endocrinol. 2006 Mar 27;248(1-2):61-71
16414178
Invest Ophthalmol Vis Sci. 2002 Nov;43(11):3365-72
12407145
J Biol Chem. 1998 Aug 21;273(34):21790-9
9705317
FEBS J. 2008 Jan;275(1):138-47
18039331
Invest Ophthalmol Vis Sci. 2004 Nov;45(11):3857-62
15505029
J Biol Chem. 2005 May 13;280(19):18822-32
15755727
Proc Natl Acad Sci U S A. 1989 Dec;86(23):9606-10
2594788
Biochemistry. 1994 Nov 22;33(46):13741-50
7947785
Chem Biol Interact. 2009 Mar 16;178(1-3):99-109
19061874
Nat Genet. 1999 Jun;22(2):188-91
10369264
Biochem J. 2009 Apr 1;419(1):113-22, 1 p following 122
19102727
Biochemistry. 2005 Sep 6;44(35):11715-21
16128572
J Biol Chem. 2005 May 27;280(21):20413-20
15790565
Biochemistry. 2005 May 10;44(18):7035-47
15865448
Vis Neurosci. 2000 Sep-Oct;17(5):667-678
11153648