INHIBITION OF ENZYMES 829 



Survey of Enzyme Inhibitions 



Some enzyme inhibitions produced by the mercurials are given in Table 

 7-13. These represent only about a fifth of the enzymes studied. It is a 

 difficult matter to decide which results should be in the table. I have tried to 

 include principally two sorts of enzyme, those that are "important" and 

 those that are inhibited "potently." But which enzymes are important? 

 Every enzyme is important for a particular pathway, or a certain organism, 

 or the investigator who studies it. The following groups of enzymes have 

 generally been chosen: those in the glycolytic Embden-Meyerhof or pen- 

 tose-? pathways, the tricarboxylate cycle, electron transport systems, phos- 

 phate transfer, and central amino acid metabolism; those often involved 

 in cell function (such as choline acetylase, cholinesterase, carbonic anhy- 

 drase, etc.); and certain classic SH enzymes (such as urease). We now must 

 consider how the word "potently" should be defined. I have arbitrarily 

 chosen enzymes inhibited significantly (usually 50% or more) by concen- 

 trations of mercurial of 0.01 mM or less, since such enzymes could usually 

 be considered as having reactive SH groups at or near the active center. 

 It is evident that a certain enzyme differs often very markedly in suscepti- 

 bility depending on the tissue or species from which it is obtained, so that 

 one cannot speak of the sensitivity of NADH oxidase, for example, in quan- 

 titative terms without specifying which NADH oxidase is meant. At least 

 most will agree I think that the enzymes included in Table 7-13 are impor- 

 tant in common metabolic pathways and/or are inhibited quite potently.* 



Another problem in presenting the inhibitions in Table 7-13 is that the 

 degree of inhibition by mercurials depends on a number of factors to a 

 greater extent than with most other inhibitors. Particularly important are 

 the pH (mainly because of competition of H+ with the mercurial for the 

 S~ group), the temperature (because of both the high temperature coeffi- 

 cients of mercurial reactions and the possibility of secondary thermal inac- 

 tivation), the composition of the medium (principally because of competi- 

 tion of anions with the S~ group for the mercurials), the period of the in- 

 cubation with the inhibitor (since in many cases the inhibition does not 

 attain a constant level), and the presence of impurities (most of which can 

 complex with the mercurials and reduce their effectiveness). There are too 

 many of these variables to include in the table. The purposes of the table 

 are to provide very roughly some information on the relative sensitivities 

 of the more important enzymes, and to present an experimental basis for 

 the appreciation of the lack of specificity of the mercurials when used in 

 complex cellular preparations. 



In addition to these problems, it is likely that many of the most notable 



* If a reader wishes to obtain information on the inhibition of an enzyme not given 

 in the table, I shall be happy to try to supply this upon receiving a written request. 



