Carbonic anhydrase inhibitors: inhibition of the membrane-bound human isozyme IV with anions

Fluoride at non-toxic dose affects odontoblast gene expression in vitro

“…Metalloproteinase-20 was less active after fluoride administration in vivo (DenBesten et al, 2002), and excess calcium in organ culture partially prevented formation of fluorotic enamel (Bronckers et al, 2006). Furthermore, also the activity of enzymes may be directly affected by fluoride, as observed for carbonic anhydrase (Innocenti et al, 2004).…”

Carbonic anhydrase inhibitors and activators and their use in therapy

“…The affinity of mCA XIII for anions is very different from that of the other cytosolic isozymes (hCA I and II) or the mitochondrial isozyme hCA V. This resistance to inhibition by the physiological anions bicarbonate and chloride suggests an evolutionary adaptation of CA XIII to the presence of high concentrations of such anions (e.g., in the reproductive tract of both female and male) and the possible participation of this isozyme (similarly to CA II, CA IV and CA V) in metabolons with proteins involved in the anion exchange and transport, such as the anion exchangers (AE1-3) or the sodium bicarbonate co-transporter (NBC1 and NBC3) proteins, which remain to be identified [31]. The membrane-associated human isozyme of carbonic anhydrase, hCA IV, has also been investigated for its interaction with anion inhibitors, for the CO 2 hydration reaction catalysed by this enzyme [32]. Surprisingly, halides were observed to act as potent hCA IV inhibitors, with inhibition constants in the range of 70 -90 µM, although most of these ions and especially fluoride, the best hCA IV inhibitor among the halides, are weak inhibitors of other isozymes, such as hCA I, II and V. The metal poisons cyanate, cyanide and hydrogen sulfide were weaker hCA IV inhibitors (K i = 0.6 -3.9 mM), whereas thiocyanate, azide, nitrate and nitrite showed even weaker inhibitory properties (K i = 30.8 -65.1 mM).…”

“…Indeed, several new isozymes have been extensively investigated in the last two years for their interaction with a multitude of anions, such as CA IV, VA, VII, IX and XIII [31][32][33][34][35][36][37]. Thus, the best murine mCA XIII inhibitors detected by Innocenti et al [31] were cyanate, thiocyanate, cyanide and sulfamide, with K i values in the range of 0.25 µM to 0.74 mM, whereas fluoride, iodide, azide, carbonate and hydrogen sulfide were less effective (K i = 3.0 -5.5 mM).…”

(In)organic anions as carbonic anhydrase inhibitors

“…Table 1 shows such inhibition data for the 13 mammalian isoforms, with the most common inorganic anions (halides, pseudohalides, nitrate, bicarbonate, carbonate, sulfate, etc. ), obtained in the same conditions, using recombinant highly purified enzymes and a stopped flow assay monitoring the physiologic reaction catalyzed by the CAs, i.e., hydration of CO 2 to bicarbonate [51][52][53][54][55][56][57][58][59][60][61][62][63][64][65][66][67][68][69].…”