Recent advances in research on the most novel carbonic anhydrases, CA XIII and XV.
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 k(cat) = 1.5 x 10(5) s(-1), k(cat)/K(M) = 1.1 x 10(7) M(-1) s(-1) and K(I) = 16 nM for human CA XIII and k(cat) = 4.7 x 10(5) s(-1), k(cat)/K(M) = 3.3 x 10(7) M(-1) s(-1) and K(I) = 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.
Hilvo
M
M
Institute of Medical Technology, University of Tampere, Biokatu 6, FIN-33014 University of Tampere, Finland. Mika.Hilvo@uta.fi
Innocenti
A
A
Monti
S M
SM
De Simone
G
G
Supuran
C T
CT
Parkkila
S
S
D000136:Acid-Base Equilibrium; D000595:Amino Acid Sequence; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D002256:Carbonic Anhydrases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000201:enzymology; D008969:Molecular Sequence Data
D002257:Carbonic Anhydrase Inhibitors; C483903:CA13 protein, human; D002256:Carbonic Anhydrases; C507974:carbonic anhydrase XV, mouse