Carbonic anhydrases.

Some of the current studies of carbonic anhydrases are directed to the genetic mechanisms underlying their synthesis. Determination of the structure of their genes will probably most readily resolve the question of whether the membrane bound forms of the enzyme represent products of additional loci other than those of the three well-known soluble forms. Extensions of our knowledge of the sequences of these isozymes as well as those from lower animals and from plants will make possible a more precise evaluation of the extent of the multigene aspects of these proteins and their evolutionary backgrounds. Studies of the interrelationships of the regulation of the transcriptional and translational processes of the well-known isozymes and in particular the effects of hormones will be of interest. Insights into modifications of the isozymes' synthetic processes occurring in various diseases should also be forth-coming from these studies. In addition to the above the applications of what are perhaps today somewhat classical methods of protein chemistry will be needed to explore the reasons for the changes in activity accompanying the sequence variations of the different isozymes, the decreases or increases in activity accompanying derivatizations of specific residues and the reasons for the differences in the activity of different inhibitors on the various isozymes. The broad specificity of these enzymes for different substrates and the ability of CA-III to hydrolyze various phenyl esters and in some cases to become derivatized also present problems in protein structural chemistry. In terms of the latter reactions, the meaning of the relationships of these activities to those of the protein ubiquitin, which is homologous to CA-III, needs clarification. It would appear that various of the protein structural studies will be aided by crystallographic investigations of not only CA-III but of various of its derivatives which undergo either increases or decreases in activity. The above areas of studies present a wide variety of problems for workers in various disciplines and backgrounds who are interested in the carbonic anhydrases.