PUBLICATION
Specificity of Zebrafish Retinol Saturase: Formation of All-trans-13,14-dihydroretinol and All-trans-7,8- dihydroretinol
- Authors
- Moise, A.R., Isken, A., Dominguez, M., Lera, A.R., Lintig, J.V., and Palczewski, K.
- ID
- ZDB-PUB-070210-34
- Date
- 2007
- Source
- Biochemistry 46(7): 1811-1820 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Catalysis
- Molecular Sequence Data
- Organ Specificity
- Oxidoreductases Acting on CH-CH Group Donors/biosynthesis
- Oxidoreductases Acting on CH-CH Group Donors/genetics
- Oxidoreductases Acting on CH-CH Group Donors/metabolism*
- Stereoisomerism
- Substrate Specificity
- Vitamin A/analogs & derivatives*
- Vitamin A/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism*
- Zebrafish Proteins/biosynthesis
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism*
- PubMed
- 17253779 Full text @ Biochemistry
- CTD
- 17253779
Citation
Moise, A.R., Isken, A., Dominguez, M., Lera, A.R., Lintig, J.V., and Palczewski, K. (2007) Specificity of Zebrafish Retinol Saturase: Formation of All-trans-13,14-dihydroretinol and All-trans-7,8- dihydroretinol. Biochemistry. 46(7):1811-1820.
Abstract
Metabolism of vitamin A, all-trans-retinol, leads to the formation of 11-cis-retinaldehyde, the visual chromophore, and all-trans-retinoic acid, which is involved in the regulation of gene expression through the retinoic acid receptor. Enzymes and binding proteins involved in retinoid metabolism are highly conserved across species. We previously described a novel mammalian enzyme that saturates the 13-14 double bond of all-trans-retinol to produce all-trans-13,14-dihydroretinol, which then follows the same metabolic fate as that of all-trans-retinol. Specifically, all-trans-13,14-dihydroretinol is transiently oxidized to all-trans-13,14-dihydroretinoic acid before being oxidized further by Cyp26 enzymes. Here, we report the identification of two putative RetSat homologues in zebrafish, one of which, zebrafish RetSat A (zRetSat A), also had retinol saturase activity, whereas zebrafish RetSat B (zRetSat B) was inactive under similar conditions. Unlike mouse RetSat (mRetSat), zRetSat A had an altered bond specificity saturating either the 13-14 or 7-8 double bonds of all-trans-retinol to produce either all-trans-13,14-dihydroretinol or all-trans-7,8-dihydroretinol, respectively. zRetSat A also saturated the 13-14 or 7-8 double bonds of all-trans-3,4-didehydroretinol (vitamin A2), a second endogenous form of vitamin A in zebrafish. The dual enzymatic activity of zRetSat A displays a newly acquired specificity for the 13-14 double bond retained in higher vertebrates and also the evolutionarily preserved activity of bacterial phytoene desaturases and plant carotenoid isomerases. Expression of zRetSat A was restricted to the liver and intestine of hatchlings and adult zebrafish, whereas zRetSat B was expressed in the same tissues but at earlier developmental stages. Exogenous all-trans-retinol, all-trans-13,14-dihydroretinol, or all-trans-7,8-dihydroretinol led to the strong induction of the expression of the retinoic acid-metabolizing enzyme, Cyp26A1, arguing for an active signaling function of dihydroretinoid metabolites in zebrafish. These findings point to a conserved function but altered specificity of RetSat in vertebrates, leading to the generation of various dihydroretinoid compounds, some of which could have signaling functions.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping