Document Detail


An enzymatic mechanism for generating the precursor of endogenous 13-cis retinoic acid in the brain.
MedLine Citation:
PMID:  21235714     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
13-cis Retinoic acid (13cRA), a stereoisomeric form of retinoic acid, is naturally generated in the body and is also used clinically to treat acute promyelocytic leukemia, some skin diseases and cancer. Furthermore, it has been suggested that 13cRA modulates brain neurochemical systems because increased 13cRA levels are correlated with depression and increased suicidal tendencies. However, the mechanism for the generation of endogenous 13cRA is not well understood. The present study identified and characterized a novel enzyme in zebrafish brain, 13-cis isomerohydrolase (13cIMH) (EC 5.2.1.7), which exclusively generated 13-cis retinol and can be oxidized to 13cRA. 13cIMH shares 74% amino acid sequence identity with human retinal pigment epithelium specific 65 kDa protein (RPE65), an 11-cis isomerohydrolase in the visual cycle, and retains the key residues essential for the isomerohydrolase activity of RPE65. Similar to RPE65, 13cIMH is a membrane-associated protein, requires all-trans retinyl ester as its intrinsic substrate, and its enzymatic activity is dependent on iron. The purified 13cIMH converted all-trans retinyl ester exclusively to 13-cis retinol with K(m)  = 2.6 μm and k(cat) = 4.4 × 10(-4) ·s(-1) . RT-PCR, western blot analysis and immunohistochemistry detected 13cIMH expression in the brain. These results suggest that 13cIMH may play a key role in the generation of 13cRA, as well as in the modulation of neuronal functions in the brain.
Authors:
Yusuke Takahashi; Gennadiy Moiseyev; Ying Chen; Krysten Farjo; Olga Nikolaeva; Jian-Xing Ma
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-03
Journal Detail:
Title:  The FEBS journal     Volume:  278     ISSN:  1742-4658     ISO Abbreviation:  FEBS J.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-03-08     Completed Date:  2011-05-09     Revised Date:  2013-07-02    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  England    
Other Details:
Languages:  eng     Pagination:  973-87     Citation Subset:  IM    
Copyright Information:
© 2011 The Authors Journal compilation © 2011 FEBS.
Affiliation:
Department of Medicine Endocrinology, Harold Hamm Oklahoma Diabetes Center, University of Oklahoma Health Sciences Center, OK, USA.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Brain / enzymology*
Carrier Proteins / chemistry
Cloning, Molecular
Eye Proteins / chemistry
Humans
Isotretinoin / metabolism*
Kinetics
Molecular Sequence Data
Sequence Homology, Amino Acid
Zebrafish
cis-trans-Isomerases / metabolism*
Grant Support
ID/Acronym/Agency:
EY012231/EY/NEI NIH HHS; EY018659/EY/NEI NIH HHS; EY019309/EY/NEI NIH HHS; P20 RR024215-01/RR/NCRR NIH HHS; P20 RR024215-01S1/RR/NCRR NIH HHS; P20 RR024215-02/RR/NCRR NIH HHS; P20 RR024215-03/RR/NCRR NIH HHS; P20 RR024215-03S1/RR/NCRR NIH HHS; P20 RR024215-04/RR/NCRR NIH HHS; P20 RR024215-05/RR/NCRR NIH HHS; P20RR024215/RR/NCRR NIH HHS; R01 EY012231/EY/NEI NIH HHS; R01 EY012231-09/EY/NEI NIH HHS; R01 EY012231-10/EY/NEI NIH HHS; R01 EY012231-11/EY/NEI NIH HHS; R01 EY012231-12/EY/NEI NIH HHS; R01 EY012231-13/EY/NEI NIH HHS; R01 EY018659/EY/NEI NIH HHS; R01 EY018659-01A1/EY/NEI NIH HHS; R01 EY018659-02/EY/NEI NIH HHS; R01 EY019309-01/EY/NEI NIH HHS; R01 EY019309-01S1/EY/NEI NIH HHS; R01 EY019309-02/EY/NEI NIH HHS; R01 EY019309-03/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/Carrier Proteins; 0/Eye Proteins; 4759-48-2/Isotretinoin; EC 3.1.1.64/retinoid isomerohydrolase; EC 5.2.-/cis-trans-Isomerases
Comments/Corrections

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