title: Renalase is an α-NAD(P)H oxidase/anomerase.
abstract: Renalase is a protein hormone secreted into the blood by the kidney that is reported to lower blood pressure and slow heart rate. Since its discovery in 2005, renalase has been the subject of conjecture pertaining to its catalytic function. While it has been widely reported that renalase is the third monoamine oxidase (monoamine oxidase C) that oxidizes circulating catecholamines such as epinephrine, there has been no convincing demonstration of this catalysis in vitro. Renalase is a flavoprotein whose structural topology is similar to known oxidases, lysine demethylases, and monooxygenases, but its active site bears no resemblance to that of any known flavoprotein. We have identified the catalytic activity of renalase as an α-NAD(P)H oxidase/anomerase, whereby low equilibrium concentrations of the α-anomer of NADPH and NADH initiate rapid reduction of the renalase flavin cofactor. The reduced cofactor then reacts with dioxygen to form hydrogen peroxide and releases nicotinamide dinucleotide product in the β-form. These processes yield an apparent turnover number (0.5 s(-1) in atmospheric dioxygen) that is at least 2 orders of magnitude more rapid than any reported activity with catechol neurotransmitters. This highly novel activity is the first demonstration of a role for naturally occurring α-NAD(P)H anomers in mammalian physiology and the first report of a flavoprotein catalyzing an epimerization reaction.
authors: Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee , 3210 N. Cramer Street, Milwaukee, Wisconsin 53211-3209, United States.
authors: Brett A
authors: BA
authors: Beaupre
authors: Brenton R
authors: BR
authors: Carmichael
authors: Matthew R
authors: MR
authors: Hoag
authors: Dhara D
authors: DD
authors: Shah
authors: Graham R
authors: GR
authors: Moran
mesh_terms: D002384:Catalysis; D006801:Humans; D008958:Models, Molecular; D008995:Monoamine Oxidase / Q000737:chemistry*; D019255:NADPH Oxidases / Q000737:chemistry*; D010084:Oxidation-Reduction; D011743:Pyrimidines / Q000737:chemistry; D013379:Substrate Specificity
chemical_list: D011743:Pyrimidines; D008995:Monoamine Oxidase; C521557:renalase; D019255:NADPH Oxidases