Kinetics and Mechanistic Implications of CO₂ Hydration Activity of Human Erythrocyte Carbonic Anhydrases

Abstract

The reversible hydration of carbon dioxide is recognized as one of the simplest physiological reactions requiring biochemical catalysis. The mechanism of its catalysis by carbonic anhydrase has, nevertheless, been the subject of unabated discussion and controversy during the last decade. This account attempts to review the major features of the catalyzed reaction and their mechanistic implications. More detailed discussions of specific aspects are discussed elsewhere in these proceedings (cf. this vol. S. Lindskog, D.N. Silverman, and others). The present review is limited largely to data on the major human erythrocyte carbonic anhydrases whose crystal structure is now known to high resolution. These are the low specific activity isozyme HCAB (or CA I) and the high specific activity isozyme HCAC (or CA II). In addition, chemically modified derivatives of both of these isozymes have been studied and are of importance to understanding the mechanism of the enzyme. It is hoped that future work will soon provide the kinetic parameters of the newly discovered muscle isozyme (cf. Tashian this vol.) and will increase the comparative kinetic data base.