The history of renalase from amine oxidase to α-NAD(P)H-oxidase/anomerase

  • I. S. Severina
  • V. I. Fedchenko
  • A. V. Veselovsky
  • A. E. Medvedev


Renalase is a recently discovered secretory protein, which plays a certain (still poorly understood) role in regulation of blood pressure. The review summarizes own and literature data on structure and catalytic properties of renalase accumulated since the first publication on this protein (2005). Initial reports on FADdependent amine oxidase activity were not confirmed in independent experiments performed in different laboratories. In addition, proposed amine oxidase activity of circulating extracellular renalase requires the presence of FAD, which has not been detected either in blood or urinary renalase. Moreover, renalase excreted into urine lacks its N-terminal peptide, which is ultimately needed for accommodation of the FAD cofactor. Results of the Aliverti’s group on NAD(P)H binding by renalase and weak diaphorase activity of this enzyme stimulated further studies of renalase as NAD(P)H oxidase catalyzing reaction of catecholamine co-oxidation. However, physiological importance of such extracellular catecholamine-metabolizing activity remains unclear due to existence of much more active enzymatic systems (e.g., neutrophil NAD(P)H oxidase, xanthine oxidase/xanthine) in circulation, which can perform such co-oxidation reactions. Recently α-NAD(P)H oxidase/anomerase activity of renalase, which also promotes oxidative conversion of β-NADH isomers inhibiting activity of NAD-dependent dehydrogenases, has been described. However, its possible contribution to the antihypertensive effect of renalase remains unclear. Thus, the antihypertensive effect of renalase still remains a phenomenon with unclear biochemical mechanim(s) and functions of intracellular and extracellular (circulating) renalases obviously differ.


renalase N-terminal peptide FAD-binding domain catalytic functions antihypertensive effect 


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Copyright information

© Pleiades Publishing, Ltd. 2016

Authors and Affiliations

  • I. S. Severina
    • 1
  • V. I. Fedchenko
    • 1
  • A. V. Veselovsky
    • 1
  • A. E. Medvedev
    • 1
  1. 1.Institute of Biomedical ChemistryMoscowRussia

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