RT Journal Article
SR Electronic
T1 Chemical properties of carbonic anhydrase IV, the membrane-bound enzyme.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 901
OP 905
VO 44
IS 4
A1 T H Maren
A1 G C Wynns
A1 P J Wistrand
YR 1993
UL http://molpharm.aspetjournals.org/content/44/4/901.abstract
AB The carbonic anhydrase (CA) isozyme (IV) in microsomes is thought to have a dominant role in secretory processes. Using microsomes from bovine kidney and lung (which had the same activity), we have measured the Km and kcat for CO2 hydration and compared these numbers with those for CA I (red blood cells and gut), CA II (red blood cells and secretory cells), and CA III (muscle). For kidney CA IV, Km is 10 mM and kcat is 170,000 sec-1 at 0 degree, approaching the rate for CA II but much greater than those for CA I or III. The Ki values for 11 sulfonamides with CA IV were measured and in all cases showed less binding (averaging 17-fold) than to CA II. This is the result of reduction of the association rate constants (k(on)), whereas the dissociation constants of the drug-enzyme complexes (k(off) are similar between CA II and IV. Based on these data, full physiological effects may be expected when inhibition of CA IV is about 99%. Anion inhibition of CA IV is similar to that of CA II and less than that of CA I or CA III. Data are compatible with the proposed role of CA IV in physiological events, i.e., HCO3- formation and secretion at one cell border and H+ separation and excretion at the other.