Is renalase a novel player in catecholaminergic signaling? The mystery of the catalytic activity of an intriguing new flavoenzyme.

摘要

Renalase is a flavoprotein recently discovered in humans, preferentially expressed in the proximal tubules of the kidney andsecreted in blood and urine. It is highly conserved in vertebrates, with homologs identified in eukaryotic and prokaryotic organisms. Severalgenetic, epidemiological, clinical and experimental studies show that renalase plays a role in the modulation of the functions of thecardiovascular system, being particularly active in decreasing the catecholaminergic tone, in lowering blood pressure and in exerting aprotective action against myocardial ischemic damage. Deficient renalase synthesis might be the cause of the high occurrence of hypertensionand adverse cardiac events in kidney disease patients. Very recently, recombinant human renalase has been structurally and functionallycharacterized in vitro. Results show that it belongs to the p-hydroxybenzoate hydroxylase structural family of flavoenzymes, containsnon-covalently bound FAD with redox features suggestive of a dehydrogenase activity, and is not a catecholamine-degrading enzyme,either through oxidase or NAD(P)H-dependent monooxygenase reactions. The biochemical data now available will hopefully providethe basis for a systematic and rational quest toward the identification of the reaction catalyzed by renalase and of the molecularmechanism of its physiological action, which in turn are expected to favor the development of novel therapeutic tools for the treatment ofkidney and cardiovascular diseases.