PMID- 24799687 OWN - NLM STAT- MEDLINE DCOM- 20140715 LR - 20211021 IS - 1091-6490 (Electronic) IS - 0027-8424 (Print) IS - 0027-8424 (Linking) VI - 111 IP - 20 DP - 2014 May 20 TI - Identification of the 11-cis-specific retinyl-ester synthase in retinal Muller cells as multifunctional O-acyltransferase (MFAT). PG - 7302-7 LID - 10.1073/pnas.1319142111 [doi] AB - Absorption of a photon by a rhodopsin or cone-opsin pigment isomerizes its 11-cis-retinaldehyde (11-cis-RAL) chromophore to all-trans-retinaldehyde (all-trans-RAL), which dissociates after a brief period of activation. Light sensitivity is restored to the resulting apo-opsin when it recombines with another 11-cis-RAL. Conversion of all-trans-RAL to 11-cis-RAL is carried out by an enzyme pathway called the visual cycle in cells of the retinal pigment epithelium. A second visual cycle is present in Muller cells of the retina. The retinol isomerase for this noncanonical pathway is dihydroceramide desaturase (DES1), which catalyzes equilibrium isomerization of retinol. Because 11-cis-retinol (11-cis-ROL) constitutes only a small fraction of total retinols in an equilibrium mixture, a subsequent step involving selective removal of 11-cis-ROL is required to drive synthesis of 11-cis-retinoids for production of visual chromophore. Selective esterification of 11-cis-ROL is one possibility. Crude homogenates of chicken retinas rapidly convert all-trans-ROL to 11-cis-retinyl esters (11-cis-REs) with minimal formation of other retinyl-ester isomers. This enzymatic activity implies the existence of an 11-cis-specific retinyl-ester synthase in Muller cells. Here, we evaluated multifunctional O-acyltransferase (MFAT) as a candidate for this 11-cis-RE-synthase. MFAT exhibited much higher catalytic efficiency as a synthase of 11-cis-REs versus other retinyl-ester isomers. Further, we show that MFAT is expressed in Muller cells. Finally, homogenates of cells coexpressing DES1 and MFAT catalyzed the conversion of all-trans-ROL to 11-cis-RP, similar to what we observed with chicken-retina homogenates. MFAT is therefore an excellent candidate for the retinyl-ester synthase that cooperates with DES1 to drive synthesis of 11-cis-retinoids by mass action. FAU - Kaylor, Joanna J AU - Kaylor JJ AD - Jules Stein Eye Institute and. FAU - Cook, Jeremy D AU - Cook JD AD - Jules Stein Eye Institute and. FAU - Makshanoff, Jacob AU - Makshanoff J AD - Jules Stein Eye Institute and. FAU - Bischoff, Nicholas AU - Bischoff N AD - Jules Stein Eye Institute and. FAU - Yong, Jennifer AU - Yong J AD - Jules Stein Eye Institute and. FAU - Travis, Gabriel H AU - Travis GH AD - Jules Stein Eye Institute andDepartment of Biological Chemistry, University of California, Los Angeles School of Medicine, Los Angeles, CA 90095 travis@jsei.ucla.edu. LA - eng GR - P30 EY000331/EY/NEI NIH HHS/United States GR - R01 EY011713/EY/NEI NIH HHS/United States GR - P30-EY00331/EY/NEI NIH HHS/United States GR - R01-EY11713/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20140505 PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Cone Opsins) RN - 0 (Esters) RN - 0 (Fatty Acids) RN - 0 (Multifunctional Enzymes) RN - 0 (Opsins) RN - EC 2.3.1.- (Acetyltransferases) RN - EC 2.3.1.76 (Retinol O-Fatty-Acyltransferase) SB - IM MH - Acetyltransferases/*metabolism MH - Animals MH - Catalysis MH - Cattle MH - Chickens MH - Cone Opsins/metabolism MH - Ependymoglial Cells/*enzymology MH - Esters/chemistry MH - Fatty Acids/chemistry MH - Gene Expression Profiling MH - Gene Expression Regulation, Enzymologic MH - HEK293 Cells MH - Humans MH - Kinetics MH - Mice MH - Multifunctional Enzymes/*metabolism MH - Opsins/metabolism MH - Retina/metabolism MH - Retinol O-Fatty-Acyltransferase/*metabolism PMC - PMC4034218 COIS- The authors declare no conflict of interest. EDAT- 2014/05/07 06:00 MHDA- 2014/07/16 06:00 PMCR- 2014/11/20 CRDT- 2014/05/07 06:00 PHST- 2014/05/07 06:00 [entrez] PHST- 2014/05/07 06:00 [pubmed] PHST- 2014/07/16 06:00 [medline] PHST- 2014/11/20 00:00 [pmc-release] AID - 1319142111 [pii] AID - 201319142 [pii] AID - 10.1073/pnas.1319142111 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 2014 May 20;111(20):7302-7. doi: 10.1073/pnas.1319142111. Epub 2014 May 5.