Carbonic anhydrase inhibitors: inhibition of human and murine mitochondrial isozymes V with anions.
In addition to sulfonamides, metal complexing anions represent the second class of inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.1). The first inhibition study of the mitochondrial isozyme CA V (of murine and human origin) with anions is reported here. Inhibition data of the cytosolic isozymes CA I and CA II as well as the membrane-bound isozyme CA IV with a large number of anionic species such as halides, pseudohalides, bicarbonate, nitrate, hydrosulfide, arsenate, sulfamate, and sulfamidate and so on, are also provided for comparison. Isozyme V has an inhibition profile by anions completely different to those of CA I and IV, but similar to that of hCA II, which may have interesting physiological consequences. Similarly to hCA II, the mitochondrial isozymes show micro-nanomolar affinity for sulfonamides such as sulfanilamide and acetazolamide.
Franchi
Marco
M
Università degli Studi di Firenze, Dipartimento di Biologia Animale e Genetica, Via Romana 17-19, 50122 Firenze, Italy.
Vullo
Daniela
D
Gallori
Enzo
E
Antel
Jochen
J
Wurl
Michael
M
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D000818:Animals; D000838:Anions / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000378:metabolism; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D024404:Carbonic Anhydrase V / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002384:Catalysis; D006801:Humans; D007527:Isoenzymes; D007700:Kinetics; D051379:Mice; D008928:Mitochondria / Q000201:enzymology*; D013449:Sulfonamides / Q000494:pharmacology
D000838:Anions; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D002245:Carbon Dioxide; D024404:Carbonic Anhydrase V