Renalase is an α-NAD(P)H oxidase/anomerase

Brett A. Beaupre, Brenton R. Carmichael, Matthew R. Hoag, Dhara D. Shah, Graham R. Moran

Research output: Contribution to journalArticlepeer-review

38 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)13980-13987
Number of pages8
JournalJournal of the American Chemical Society
Volume135
Issue number37
DOIs
StatePublished - Sep 18 2013
Externally publishedYes

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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