752 7. MERCURIALS 



combinations of mercury with proteins occur, and that denaturation and 

 precipitation are by no means a general phenomenon. These definite com- 

 plexes in most cases are formed through the SH groups of the proteins, and 

 methods whereby these groups may be titrated quantitatively with the 

 mercurials have been devised. Some may feel that a discussion of the com- 

 plexes of mercury with the proteins is out of place in a book on metabolic 

 inhibition, but actually much can be learned from the thorough and illu- 

 minating investigations on mercaptalbumin, hemoglobin, and other pro- 

 teins reported in the past few years. One must also realize that in any 

 system containing nonenzymic proteins, particularly cellular preparations, 

 reaction of mercury with these proteins not only may have definite effects 

 on the enzyme inhibition, but may be responsible, at least in part, for me- 

 tabolic or functional changes.* 



Protein Groups Reacting with Mercurials 



The mercurials react rapidly with certain free and exposed protein SH 

 groups, more slowly with others, and not at all with some which are pre- 

 sumably buried within the protein structure or otherwise sterically unavail- 

 able (page 643). Many SH groups react only after denaturation of the pro- 

 tein, a process which apparently exposes them for attack by the mercurials. 

 Since mercurials often initiate denaturation, they may produce a progressive 

 unloosening of the protein structure and themselves make available SH 

 groups originally unreactive, the process continuing until it is irreversible, 

 the reformation of the normal configuration not being possible when the 

 mercurial is removed. Much work with proteins and enzymes, to be dis- 

 cussed later, provides evidence that SH groups are the primary site of 

 mercurial binding, and often the only site under certain conditions. The 

 problem to be considered here is whether protein groups other than SH 

 can under any circumstances contribute to the binding. 



Examination of the constants for the complexing of mercurials with SH 

 groups and with groups normally present in proteins leads to the immediate 



* There is some inherent and unavoidable difficulty and ambiguity in the terminology 

 of the mercurials. If one uses the inorganic HgClj, how should the inhibitor be desig- 

 nated — as HgCU, Hg, Hg++, Hg", or otherwise? We have seen that in most, if not 

 all, media the mercuric ion will exist in a variety of complexes, probably of different 

 reactivities, so that it is impossible to designate the situation accurately. Similar 

 problems arise with other heavy metal ions, e.g., copper and zinc. We shall, therefore, 

 arbitrarily designate inorganic divalent mercury as Hg++, without implying that 

 this is either a predominant form or an active form. It is fundamentally and finally 

 the Hg++ ion which complexes and reacts with the various substances present, so that 

 when this is so written it must be understood that all of the complexes are implied. 

 The designation of the organic mercurials as 79-MB, PM, etc., similarly is noncommittal 

 with respect to the forms present or active. 



