CARBONIC ANHYDRASE:ISOENZYMES. PROPERTIES. DISTRIBUTION. AND FUNCTIONAL SIGNIFICANCE
Authors: CARTER M. J. 
Published: January 2008

1. Carbonic anhydrases from vertebrates, plants and bacteria have molecular weights of 30,000 (or multiples thereof), contain one zinc atom per 30,000 molecular weight, and are inhibited by acetazolamide and related compounds.

2. In mammals, there are two major isoenzymes of carbonic anhydrase. The so‐called ‘high activity’ carbonic anhydrase possesses a carbon dioxide‐hydratase activity many times (in the case of the guinea‐pig isoenzymes, 18 times) that of the ‘low activity’ isoenzyme.

3. The mammalian isoenzymes differ from one another in their amino‐acid compositions (the difference in serine contents being a consistent finding in a number of species), in their physical properties (isoelectric pH, retention by ion‐exchange resins, electrophoretic mobility) and in their kinetic properties.

4. Mammalian carbonic anhydrases also catalyse the hydrolysis of some esters and the hydration of aldehydes. Their relative activities with these other substrates may be substantially different from their relative activities with carbon dioxide as substrate. The discovery that carbonic anhydrase may also catalyse other reactions raises the possibility that the enzyme may have other roles in metabolic pathways (e.g., in certain dehydrogenation reactions).

5. In plants, the role of carbonic anhydrase may be to catalyse the inter‐conversion of bicarbonate and carbon dioxide, to provide ‘carbon dioxide’ in the form appropriate for carbon‐fixing reactions. A similar role has been suggested for the carbonic anhydrase found in Neissariae.

6. The carbonic anhydrase of vertebrates (the ‘high activity’ isoenzyme of mammals) is found in many ion‐transporting epithelia, but its role in them is still uncertain. It occurs in acid‐transporting epithelia such as the stomach and kidney, and also in certain bicarbonate‐transporting epithelia like the large intestine. There is, however, a poor correlation between the presence of the enzyme and the occurrence of acid or bicarbonate secretion. Thus there is little or no carbonic anhydrase in some tissues noted for their ability to secrete bicarbonate ions, such as the pancreas and ileum. Conversely, carbonic anhydrase‐containing tissues like the avian salt gland and the elasmobranch rectal gland form concentrated sodium chloride solutions which are of nearly neutral pH. The correlation between the distribution of carbonic anhydrase and the occurrence of active chloride transport appears similar to that between carbonic anhydrase and bicarbonate ion transport.

7. While the red cells of most mammalian species so far studied contain both ‘high activity’ and ‘low activity’ isoenzymes, the latter is reported to be absent from the erythrocytes of sheep, ox and dog. Presumably the ‘low activity’ isoenzyme is not necessary for an adequate rate of carbon dioxide exchange to occur between tissues and lungs in these species.

8. The ‘low activity’ isoenzyme is present in tissues other than blood, for example, the colon, caecum and ox rumen, and probably also, the gall bladder and kidney medulla. Its distribution differs markedly from that of the ‘high activity’ isoenzyme and presumably it has a particular functional importance of its own. It is not possible to define the role of the ‘low activity’ isoenzyme at present, but attention is drawn to the possibility that it is concerned in the handling of the products of microbial fermentation, such as ammonia and organic acids, by the large intestines and ruminant forestomach.

My work on the isoenzymes of carbonic anhydrase was supported by a Medical Research Council Scholarship, and by an equipment grant to Dr D. S. Parsons. I am also grateful to Dr D. S. Parsons for his comments on the manuscript.