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J. Lipid Res.
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Originally published In Press as doi:10.1194/jlr.M000950 on August 31, 2009

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Journal of Lipid Research, Vol. 50, 2514-2523, December 2009
Copyright © 2009 by American Society for Biochemistry and Molecular Biology

Esterase 22 and beta-glucuronidase hydrolyze retinoids in mouse liver

Renate Schreiber, Ulrike Taschler, Heimo Wolinski, Andrea Seper, Stefanie N. Tamegger, Maria Graf, Sepp D. Kohlwein, Guenter Haemmerle, Robert Zimmermann, Rudolf Zechner1 and Achim Lass1

Institute of Molecular Biosciences, University of Graz, 8010 Graz, Austria

1 To whom correspondence should be addressed. e-mail: achim.lass{at}uni-graz.at; rudolf.zechner{at}uni-graz.at

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 β-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 β-glucuronide. In conclusion, our observations implicate that both Es22 and Gus play a role in liver retinoid metabolism.

Supplementary key words vitamin A • retinol • retinyl ester hydrolase • endoplasmic reticulum

Abbreviations: ARAT, acyl-CoA:retinol acyltransferase; BHT, butylated hydroxytoluene; CE, cholesteryl oleate; CEL, carboxyl ester lipase; ER, endoplasmic reticulum; Es22, esterase 22; GFP, green fluorescent protein; Gus, β-glucuronidase; KID, kidney; LacZ, β-galactosidase; LRAT, lecithin:retinol acyltransferase; MOMA, monocyte-macrophage antibody; RAG, retinoyl β-glucuronide; RBP4, retinol binding protein 4; RE, retinyl ester; REH, retinyl ester hydrolase; RFP, red fluorescent protein; {alpha}-SMA, alpha smooth muscle actin; TBST, Tris/NaCl/Tween-20; TG, triglyceride


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