ライフサイエンスコーパス: 11-cis-retinol

1 H]-retinol generated both retinyl esters and 11-cis retinol.

2 ize remaining enzymatic activities oxidizing 11-cis-retinol.

3 which converts all-trans-retinyl ester into 11-cis-retinol.

4 s than isomerization of all-trans-retinol to 11-cis-retinol.

5 lls where all-trans-retinol is isomerized to 11-cis-retinol.

6 hich processes all-trans-retinyl esters into 11-cis-retinol.

7 on of all-trans-retinyl fatty acid esters to 11-cis-retinol.

8 all-trans-retinol visual chromophore back to 11-cis-retinol.

9 ate, from the lipid bilayer for synthesis of 11-cis-retinol.

10 cts interconversion of all-trans-retinol and 11-cis-retinol.

11 ll-trans-retinyl esters as the precursors of 11-cis-retinol.

12 so establish that tREs are the precursors to 11-cis-retinol.

13 not all-trans-retinol, are the precursors of 11-cis-retinol.

14 Because 11-cis-retinol (11-cis-ROL) constitutes only a small fra

15 Furthermore, this 11-cis-retinol/11-cis-retinal-specific binding protein p

16 gment epithelium and generates predominantly 11-cis-retinol (11cROL) and a minor amount of 13-cis-ret

17 al cycle in Muller cells supplies cones with 11-cis-retinol (11cROL) chromophore precursor at high ra

18 on of all-trans retinyl fatty acid esters to 11-cis-retinol (11cROL) in the visual cycle, controls th

19 ol dehydrogenases (11-cis-RDHs) that oxidize 11-cis-retinol (11cROL) to 11-cis-retinaldehyde (11cRAL)

20 hich recognizes as substrates 9-cis-retinol, 11-cis-retinol, 5 alpha-androstan-3 alpha,17 beta-diol a

21 hich recognizes as substrates 9-cis-retinol, 11-cis-retinol, 5alpha-androstan-3alpha,17beta-diol, and

22 ase that converts all-trans-retinyl ester to 11-cis-retinol, a key reaction in the retinoid visual cy

23 m, which converts all-trans-retinyl ester to 11-cis-retinol, a key step in the retinoid visual cycle.

24 n the rod visual cycle where it serves as an 11-cis-retinol acceptor for the enzymatic isomerization

25 In contrast, 11-cis-retinol activates the expressed salamander and hu

26 lpha-hydroxysteroid dehydrogenase activity), 11-cis-retinol, all-trans-retinol, and 9-cis-retinol, wi

27 pigment epithelium where it is converted to 11- cis-retinol and oxidized to 11- cis-retinal before i

28 nd it displays stereospecific preference for 11-cis-retinol and 13-cis-retinol but is much less effic

29 Oxidation was specific for 11-cis-retinol and 9-cis-retinol.

30 This reaction is unique in that 1) both 11-cis-retinol and all-trans-retinal were required to pr

31 the enzymatic isomerization of all-trans- to 11-cis-retinol and as a substrate carrier for 11-cis-ret

32 nol dehydrogenase, is pro-S-specific to both 11-cis-retinol and NADH.

33 l acyltransferase, for RPE65 in synthesis of 11-cis-retinol, and its identity as the isomerohydrolase

34 ation of all-trans-retinol, isomerization to 11-cis-retinol, and oxidation to 11-cis-retinal occur in

35 All -trans-retinal, all -trans-retinol, and 11- cis-retinol are all agonists with all -trans-retinal

36 otein (CRALBP) carries 11-cis-retinal and/or 11-cis-retinol as endogenous ligands in the retinal pigm

37 branes synthesized 11-cis-retinyl ester from 11-cis-retinol at a rate which was 20-fold higher than t

38 retinyl palmitate binds with a K(D) = 14 nM, 11-cis-retinol binds with a K(D) = 3.8 nM, and all-trans

39 rameters were observed for RDH5 oxidation of 11-cis-retinol bound to rCRALBP mutants M222A, M225A, an

40 The reduction of 11-cis-retinal to 11-cis-retinol by cRDH enhanced the net photoisomerizati

41 rase (LRAT) on vitamin A, are processed into 11-cis-retinol by isomerohydrolase.

42 m and not the rod photoreceptor cell because 11- cis-retinol can act as an agonist and activate the s

43 ied and molecularly cloned; here we focus on 11-cis retinol dehydrogenase (encoded by the gene RDH5;

44 identified by mass spectrometric analysis as 11-cis-retinol dehydrogenase (cRDH), and enzymatic assay

45 minor phenotype associated with mutations in 11-cis-retinol dehydrogenase (RDH5) causing fundus albip

46 1-cis-retinol and as a substrate carrier for 11-cis-retinol dehydrogenase (RDH5).

47 ought to function as a substrate carrier for 11-cis-retinol dehydrogenase in the synthesis of 11-cis-

48 and regeneration of rhodopsin by inhibiting 11-cis-retinol dehydrogenase in the visual cycle.

49 is largely catalyzed by abundantly expressed 11-cis-retinol dehydrogenase, is pro-S-specific to both

50 the visual cycle component, RDH11, encoding 11-cis-retinol dehydrogenase, was observed in PYGM-null

51 visual cycle and as a substrate carrier for 11-cis-retinol dehydrogenase.

52 se, an 11-cis-retinyl-ester synthase, and an 11-cis-retinol dehydrogenase.

53 Recombinant mutant 11-cis retinol dehydrogenases had reduced activity compa

54 in the retinoid visual cycle is catalyzed by 11-cis-retinol dehydrogenases (11-cis-RDHs) that oxidize

55 This reaction is catalyzed by 11-cis-retinol dehydrogenases (11-cis-RDHs), prior to th

56 s accomplished by a family of enzymes termed 11-cis-retinol dehydrogenases, including RDH5 and RDH11.

57 nase-10 (Rdh10) convert all-trans-retinol to 11-cis-retinol during exposure to visible light.

58 ved in the production of 11-cis-retinal from 11-cis-retinol during regeneration of the cone visual pi

59 out the trans to cis isomerization producing 11-cis-retinol during the operation of the visual cycle

60 g protein in the subretinal space that binds 11-cis-retinol endogenously.

61 e65(-/-) retinas, we show that IRBP delivers 11-cis-retinol for oxidation in cones and improves the e

62 ition of retinol binding proteins stimulates 11-cis-retinol formation by a factor of approximately 13

63 l esters (tREs) are the direct precursors of 11-cis-retinol formation in chicken retinyl pigment epit

64 hyde binding protein (CRALBP) both stimulate 11-cis-retinol formation to the same extent, although CR

65 e, a specific and effective inhibitor of the 11-cis-retinol formation, also inhibits the production o

66 Phe-526 and Tyr-338, like Phe-103, decreases 11-cis-retinol formation, whereas increasing the 13-cis

67 ed the generation of both retinyl esters and 11-cis retinol from all-trans retinol.

68 isual cycle by functioning as an acceptor of 11-cis-retinol from the isomerohydrolase reaction.

69 d supply of 11-cis-retinal to cones by using 11-cis-retinol generated in Muller cells.

70 11-cis-retinol had no significant effect on the activity

71 11-cis-retinol has previously been shown in physiologica

72 which converts an all-trans-retinyl ester to 11-cis-retinol, has never been identified.

73 n that RPE65 is critical for regeneration of 11-cis retinol in the visual cycle, the function of RPE6

74 enzyme converting all-trans retinyl ester to 11-cis retinol in the visual cycle.

75 to cones by preserving the isomeric state of 11-cis-retinol in light.

76 conversion of all-trans-retinyl palmitate to 11-cis-retinol in microsomes from bovine RPE cells.

77 reaction that generates 11-cis-retinal from 11-cis-retinol in the carp retina.

78 support a role for CRALBP as an acceptor of 11-cis-retinol in the isomerization reaction of the visu

79 l pigment epithelium (RPE) as an acceptor of 11-cis-retinol in the isomerization step of the rod visu

80 how that IRBP protects the isomeric state of 11-cis-retinol in the presence of light.

81 isomerization of all-trans-retinyl ester to 11-cis-retinol in the retinal pigment epithelium (RPE) i

82 he conversion of all-trans-retinyl esters to 11-cis-retinol in the retinal pigment epithelium (RPE).

83 rsion of all-trans-retinyl ester (atRE) into 11-cis-retinol in the retinal visual cycle.

84 is isomerization of an all-trans retinoid to 11-cis-retinol in the RPE.

85 1-cis-retinal stronger than the oxidation of 11-cis-retinol, in accord with its higher affinity for 1

86 nto transducin as an index of activity, that 11-cis-retinol inactivates expressed salamander cone ops

87 isomerization occurs in vivo using exogenous 11-cis-retinol injected into the intravitreal space of w

88 In the classic retinoid cycle, 11-cis retinol is synthesized in the retinal pigment epi

89 l Rpe65 gene, isomerization of all-trans- to 11-cis-retinol is blocked.

90 dicating that isomerization of all-trans- to 11-cis-retinol is impaired.

91 This conversion is inhibited when 11-cis-retinol is in a complex with cellular retinaldehy

92 pool is radioactively labeled, the resulting 11-cis-retinol is labeled with the same specific activit

93 isomerization of all-trans-retinyl esters to 11-cis-retinol is mediated by the retinoid isomerohydrol

94 These results demonstrate that 11-cis-retinol is not a useful substrate for rod photore

95 This 11-cis-retinol is oxidized selectively in cones to the 1

96 Also, 11-cis-retinol is shown to inhibit isomerohydrolase, pro

97 In the cycle, 11-cis-retinol is transported from Muller cells to cone

98 isomerization of all-trans-retinyl esters to 11-cis-retinol, is also the isomerase enzyme responsible

99 e presence of binding proteins [44.3 pmol of 11-cis-retinol min-1 (mg of protein)-1] suggests that th

100 al pigment epithelial membranes [3.5 pmol of 11-cis-retinol min-1 (mg of protein)-1], and only small

101 is transported out of the cell; oxidation of 11- cis-retinol occurs in the retinal pigment epithelium

102 n additional unidentified enzyme(s) oxidizes 11-cis-retinol or that an alternative pathway contribute

103 omerohydrolase RPE65 (RPE65) and facilitates 11-cis-retinol oxidation to 11-cis-retinal.

104 ion was significant, amounting to >2 nmol of 11-cis-retinol per culture.

105 nduced isomerization of all-trans-retinol to 11-cis-retinol proceeds with inversion of configuration

106 n probably exerts its effect by trapping the 11-cis-retinol product.

107 product, as originally modeled, but also an 11-cis-retinol product.

108 The 11-cis retinol production correlated with the retinyl es

109 A(2) treatment, but the observed decline in 11-cis-retinol production did not directly reflect inhib

110 treatment with 11-cis-retinol, we show that 11-cis-retinol promotes pigment formation.

111 ntrast to the enzymatic all-trans-retinol to 11-cis-retinol reaction.

112 the enzyme responsible for the oxidation of 11-cis-retinol remains unknown.

113 Intervention with 11-cis-retinol restored the regeneration of 11-REs in th

114 , the specific radioactivity of newly formed 11-cis-retinol stayed constant during the course of the

115 is that in normal RPE, 11-cis retinal and/or 11-cis retinol stimulate the efflux of all-trans retinol

116 visual pigment regeneration with the use of 11-cis-retinol supplied from Muller cells.

117 photopic conditions, and it is possible that 11-cis-retinol supplies are disrupted in the absence of

118 rentially produces 13-cis-retinol instead of 11-cis-retinol, supporting a carbocation/radical cation

119 t protein-4 (FATP4), a negative regulator of 11-cis-retinol synthesis catalyzed by RPE65, increased t

120 The basal rate of 11-cis-retinol synthesis from all-trans-retinyl esters i

121 lock tRE synthesis from vitamin A also block 11-cis-retinol synthesis.

122 Our results show that the retina produces 11-cis retinol that can be oxidized and used for pigment

123 tinol at least 10-fold more efficiently than 11-cis-retinol, the precursor to the visual chromophore.

124 hindrance with a proton in position C(10) of 11-cis-retinol; thus, removal of this group could accele

125 been proposed to catalyse the conversion of 11-cis retinol to 11-cis retinal.

126 The oxidation of 11-cis-retinol to 11-cis-retinal in the retinal pigment

127 Oxidation of 11-cis-retinol to 11-cis-retinal is accomplished by a fa

128 l chromophore production is the oxidation of 11-cis-retinol to 11-cis-retinal.

129 es can catalyze the reverse isomerization of 11-cis-retinol to all-trans-retinol (and 13-cis-retinol)

130 The activation energy for the conversion of 11-cis-retinol to all-trans-retinol is 19.5 kcal/mol, an

131 P plays an important role in the delivery of 11-cis-retinol to cones and can facilitate cone function

132 thesis that IRBP facilitates the delivery of 11-cis-retinol to cones by preserving the isomeric state

133 l membrane were incubated with all-trans- or 11-cis-retinol to study retinyl ester synthesis.

134 In Muller cells, esterification of 11-cis-retinol was four times greater than esterificatio

135 hing and following subsequent treatment with 11-cis-retinol, we show that 11-cis-retinol promotes pig

136 in retinal pigment epithelium, oxidation of 11-cis-retinol, which is largely catalyzed by abundantly

137 dy was to evaluate the direct interaction of 11-cis-retinol with expressed human and salamander cone

138 inyl palmitate with RPE microsomes generated 11-cis retinol without any detectable production of all-