title: Human DHRS7, promising enzyme in metabolism of steroids and retinoids?
abstract: The metabolism of steroids and retinoids has been studied in detail for a long time, as these compounds are involved in a broad spectrum of physiological processes. Many enzymes participating in the conversion of such compounds are members of the short-chain dehydrogenase/reductase (SDR) superfamily. Despite great effort, there still remain a number of poorly characterized SDR proteins. According to various bioinformatics predictions, many of these proteins may play a role in the metabolism of steroids and retinoids. Dehydrogenase/reductase (SDR family) member 7 (DHRS7) is one such protein. In a previous study, we determined DHRS7 to be an integral membrane protein of the endoplasmic reticulum facing the lumen which has shown at least in vitro NADPH-dependent reducing activity toward several eobiotics and xenobiotics bearing a carbonyl moiety. In the present paper pure DHRS7 was used for a more detailed study of both substrate screening and an analysis of kinetics parameters of the physiologically important substrates androstene-3,17-dione, cortisone and all-trans-retinal. Expression patterns of DHRS7 at the mRNA as well as protein level were determined in a panel of various human tissue samples, a procedure that has enabled the first estimation of the possible biological function of this enzyme. DHRS7 is expressed in tissues such as prostate, adrenal glands, liver or intestine, where its activity could be well exploited. Preliminary indications show that DHRS7 exhibits dual substrate specificity recognizing not only steroids but also retinoids as potential substrates and could be important in the metabolism of these signalling molecules.
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. Electronic address: hana.stambergova@faf.cuni.cz.
authors.forename: Hana
authors.initials: H
authors.lastname: Štambergová
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. Electronic address: zemanol9@faf.cuni.cz.
authors.forename: Lucie
authors.initials: L
authors.lastname: Zemanová
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. Electronic address: lundovat@faf.cuni.cz.
authors.forename: Tereza
authors.initials: T
authors.lastname: Lundová
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. Electronic address: malcekob@faf.cuni.cz.
authors.forename: Beata
authors.initials: B
authors.lastname: Malčeková
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. Electronic address: skara3aa@faf.cuni.cz.
authors.forename: Adam
authors.initials: A
authors.lastname: Skarka
authors.affiliation: Institute of Legal Medicine, Faculty of Medicine in Hradec Králové, Charles University in Prague and University Hospital in Hradec Králové, Sokolská 581, 50005 Hradec Králové, Czech Republic. Electronic address: safrM@lfhk.cuni.cz.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Šafr
authors.affiliation: Department of Biochemical Sciences, Faculty of Pharmacy in Hradec Králové, Charles University in Prague, Heyrovského 1203, CZ-50005 Hradec Králové, Czech Republic. Electronic address: vladimir.wsol@faf.cuni.cz.
authors.forename: Vladimír
authors.initials: V
authors.lastname: Wsól
mesh_terms: D000735:Androstenedione / Q000378:metabolism; D002942:Circular Dichroism; D003348:Cortisone / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007700:Kinetics; D010088:Oxidoreductases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D010802:Phylogeny; D012172:Retinaldehyde / Q000378:metabolism; D013256:Steroids / Q000378:metabolism*
chemical_list: D013256:Steroids; D000735:Androstenedione; C000607165:DHRS7 protein, human; C571716:DHRS7c protein, human; D010088:Oxidoreductases; D012172:Retinaldehyde; D003348:Cortisone
keywords: Carbonyl reduction; DHRS7; Metabolism; Retinoids; SDR; Steroids