TY - JOUR
T1 - Recent advances in research on the most novel carbonic anhydrases, CA XIII and XV
AU - Parkkila, S.
AU - Supuran, C.T.
AU - Innocenti, A.
AU - Monti, S.M.
AU - De Simone, G.
AU - Hilvo, Mika
PY - 2008
Y1 - 2008
N2 - The carbonic anhydrase (CA) enzyme family consists of thirteen active isozymes in mammals. The most recently characterized members of this family are cytosolic CA XIII and membrane-bound CA XV. This article describes recent advances in the CA family, especially CA XIII and XV. We have also included catalytic activity data on human CA XIII and mouse CA XV. Additionally, the inhibition constants of acetazolamide toward these isozymes were determined to be kcat = 1.5 x 105 s-1, kcat/KM = 1.1 x 107 M-1s-1 and KI = 16 nM for human CA XIII and kcat= 4.7 x 105 s-1, kcat/KM = 3.3 x 107 M-1s-1 and KI = 72 nM for mouse CA XV. Although the activity of CA XIII is the second lowest reported thus far for any of the human CAs, it may have a role in maintaining the acid-base balance in the kidney and the gastrointestinal and reproductive tracts. CA XV is an exceptional enzyme, as it seems to be active in numerous species, such as rodents, birds and fish, but is absent from humans and chimpanzees. Mouse CA XV is a moderately active enzyme, suggesting that it may play a physiological role at least in the kidney. It is likely that other isozymes have substituted for this protein in humans. In addition to the novel data on CA XIII and XV, we present the catalytic activities as well as inhibition constants of acetazolamide for all mammalian CA isozymes in this review.
AB - The carbonic anhydrase (CA) enzyme family consists of thirteen active isozymes in mammals. The most recently characterized members of this family are cytosolic CA XIII and membrane-bound CA XV. This article describes recent advances in the CA family, especially CA XIII and XV. We have also included catalytic activity data on human CA XIII and mouse CA XV. Additionally, the inhibition constants of acetazolamide toward these isozymes were determined to be kcat = 1.5 x 105 s-1, kcat/KM = 1.1 x 107 M-1s-1 and KI = 16 nM for human CA XIII and kcat= 4.7 x 105 s-1, kcat/KM = 3.3 x 107 M-1s-1 and KI = 72 nM for mouse CA XV. Although the activity of CA XIII is the second lowest reported thus far for any of the human CAs, it may have a role in maintaining the acid-base balance in the kidney and the gastrointestinal and reproductive tracts. CA XV is an exceptional enzyme, as it seems to be active in numerous species, such as rodents, birds and fish, but is absent from humans and chimpanzees. Mouse CA XV is a moderately active enzyme, suggesting that it may play a physiological role at least in the kidney. It is likely that other isozymes have substituted for this protein in humans. In addition to the novel data on CA XIII and XV, we present the catalytic activities as well as inhibition constants of acetazolamide for all mammalian CA isozymes in this review.
UR - http://www.scopus.com/inward/record.url?eid=2-s2.0-42149147893&partnerID=MN8TOARS
U2 - 10.2174/138161208783877811
DO - 10.2174/138161208783877811
M3 - Article
SN - 1381-6128
VL - 14
SP - 672
EP - 678
JO - Current Pharmaceutical Design
JF - Current Pharmaceutical Design
IS - 7
ER -