title: Esterase 22 and beta-glucuronidase hydrolyze retinoids in mouse liver.
abstract: Excess dietary vitamin A is esterified with fatty acids and stored in the form of retinyl ester (RE) predominantly in the liver. According to the requirements of the body, liver RE stores are hydrolyzed and retinol is delivered to peripheral tissues. The controlled mobilization of retinol ensures a constant supply of the body with the vitamin. Currently, the enzymes catalyzing liver RE hydrolysis are unknown. In this study, we identified mouse esterase 22 (Es22) as potent RE hydrolase highly expressed in the liver, particularly in hepatocytes. The enzyme is located exclusively at the endoplasmic reticulum (ER), implying that it is not involved in the mobilization of RE present in cytosolic lipid droplets. Nevertheless, cell culture experiments revealed that overexpression of Es22 attenuated the formation of cellular RE stores, presumably by counteracting retinol esterification at the ER. Es22 was previously shown to form a complex with beta-glucuronidase (Gus). Our studies revealed that Gus colocalizes with Es22 at the ER but does not affect its RE hydrolase activity. Interestingly, however, Gus was capable of hydrolyzing the naturally occurring vitamin A metabolite retinoyl beta-glucuronide. In conclusion, our observations implicate that both Es22 and Gus play a role in liver retinoid metabolism.
authors.affiliation: Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria.
authors.forename: Renate
authors.initials: R
authors.lastname: Schreiber
authors.forename: Ulrike
authors.initials: U
authors.lastname: Taschler
authors.forename: Heimo
authors.initials: H
authors.lastname: Wolinski
authors.forename: Andrea
authors.initials: A
authors.lastname: Seper
authors.forename: Stefanie N
authors.initials: SN
authors.lastname: Tamegger
authors.forename: Maria
authors.initials: M
authors.lastname: Graf
authors.forename: Sepp D
authors.initials: SD
authors.lastname: Kohlwein
authors.forename: Guenter
authors.initials: G
authors.lastname: Haemmerle
authors.forename: Robert
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Rudolf
authors.initials: R
authors.lastname: Zechner
authors.forename: Achim
authors.initials: A
authors.lastname: Lass
mesh_terms: D000818:Animals; D019556:COS Cells; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism*; D002522:Chlorocebus aethiops; D005966:Glucuronidase / Q000378:metabolism*; D006868:Hydrolysis; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012176:Retinoids / Q000378:metabolism*
chemical_list: D012176:Retinoids; D002265:Carboxylic Ester Hydrolases; D005966:Glucuronidase