title: Kinetic features of carbonyl reductase 1 acting on glutathionylated aldehydes.
abstract: The attempt to evaluate the human carbonyl reductase 1 (CBR1) activity on 3-glutathionylated-4-hydroxyalkanals through the classical spectrophotometric assay, in which NADPH oxidation is monitored at 340 nm, failed. This was due to the ability of the enzyme to catalyze the reduction of the free aldehyde form and at the same time the oxidation of the hemiacetal structure of this class of substrates, thus leading to the occurrence of a disproportion reaction sustained by a redox recycle of the pyridine cofactor. Making use of glutathionylated alkanals devoid of the 4 hydroxyl group, and thus unable to structurally arrange into a cyclic hemiacetal form, the susceptibility to inhibition of CBR1 to polyphenols was tested. Flavones, that were much more effective than isoflavones, resulted able to modulate the reductase activity of the enzyme on this new peculiar class of substrates.
authors.affiliation: University of Pisa, Department of Biology, Biochemistry Unit, Via S. Zeno, 51, Pisa, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Moschini
authors.affiliation: University of Pisa, Department of Biology, Biochemistry Unit, Via S. Zeno, 51, Pisa, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Rotondo
authors.affiliation: Proteomics & Mass Spectrometry Laboratory, ISPAAM-CNR, Via Argine, 1085, Napoli, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Renzone
authors.affiliation: University of Pisa, Department of Biology, Biochemistry Unit, Via S. Zeno, 51, Pisa, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Balestri
authors.affiliation: University of Pisa, Department of Biology, Biochemistry Unit, Via S. Zeno, 51, Pisa, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Cappiello
authors.affiliation: Proteomics & Mass Spectrometry Laboratory, ISPAAM-CNR, Via Argine, 1085, Napoli, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Scaloni
authors.affiliation: University of Pisa, Department of Biology, Biochemistry Unit, Via S. Zeno, 51, Pisa, Italy.
authors.forename: Umberto
authors.initials: U
authors.lastname: Mura
authors.affiliation: University of Pisa, Department of Biology, Biochemistry Unit, Via S. Zeno, 51, Pisa, Italy. Electronic address: antonella.delcorso@unipi.it.
authors.forename: Antonella
authors.initials: A
authors.lastname: Del-Corso
mesh_terms: D000429:Alcohol Oxidoreductases / Q000737:chemistry / Q000378:metabolism*; D000447:Aldehydes / Q000737:chemistry / Q000378:metabolism*; D055162:Biocatalysis; D005978:Glutathione / Q000031:analogs & derivatives / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D013058:Mass Spectrometry; D059808:Polyphenols / Q000737:chemistry / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: C000605761:3-glutathionyl-4-hydroxynonanal; D000447:Aldehydes; D059808:Polyphenols; D000429:Alcohol Oxidoreductases; C531129:CBR1 protein, human; D005978:Glutathione
keywords: 3-Glutathionyl-4-hydroxyalkanals; 4-Hydroxy-2-nonenal; Carbonyl reductase 1; Short chain dehydrogenase/reductase