Carbonic anhydrase II does not exhibit Nitrite reductase or Nitrous Anhydrase Activity

Carbonic anhydrase II (CA II) is a zinc metalloenzyme that catalyzes the reversible interconversion of water and CO2 to bicarbonate and a proton. CA II is abundant in most cells, and plays a role in numerous processes including gas exchange, epithelial ion transport, respiration, extra- and intracel...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Free radical biology & medicine 2018-03, Vol.117, p.1-5
Hauptverfasser: Andring, Jacob T., Lomelino, Carrie L., Tu, Chingkuang, Silverman, David N., McKenna, Robert, Swenson, Erik R.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung:Carbonic anhydrase II (CA II) is a zinc metalloenzyme that catalyzes the reversible interconversion of water and CO2 to bicarbonate and a proton. CA II is abundant in most cells, and plays a role in numerous processes including gas exchange, epithelial ion transport, respiration, extra- and intracellular pH control, and vascular regulation. Beyond these CO2 and pH-linked roles, it has been postulated that CA II might also reduce nitrite (NO2-) to nitric oxide (NO), as bicarbonate and NO2- both exhibit sp2 molecular geometry and NO also plays an important role in vasodilation and regulation of blood pressure. Indeed, previous studies by Aamand et al. have shown that bovine CA II (BCA II) possesses nitrite dehydration activity and paradoxically demonstrated that CA inhibitors (CAIs) such as dorzolamide and acetazolamide significantly increased NO production (Aamand et al., 2009; Nielsen and Fago, 2015) [1,2]. Hence, the goal of this work was to revisit these studies using the same experimental conditions as Aamand et al. measuring NO generation by two methods, and to examine the structure of CA II in complex with NO2- in the presence and absence of dorzolamide. Our results contradict the previous findings and indicate that CA II does not exhibit nitrite reductase or dehydration activity, and that this is not enhanced in the presence of CA inhibitors. In addition, a structural examination of BCA II in complex with NO2- and superimposed with dorzolamide demonstrates that CA inhibitor binding at the active site to the zinc moiety blocks potential NO2- binding. [Display omitted] •Membrane inlet mass spectrometry and NO electrode measurements show tCA has no nitrite reductase or nitrous anhydrase activity.•There is no potentiation of CA-mediated nitrite reductase or nitrous anhydrase activity by the CA inhibitor, dorzolamide.•Structural examination of the CA II active site shows no ability to bind nitrite to the zinc in the presence of dorzolamide.
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2018.01.015