REACTIONS OF FIXATIVES WITH PROTEINS. 2 51 



keeping a small and fairly regular distance from one another, with 

 water every\vhere intervening between one and the next except 

 where they actually adhere. When denaturation has taken place, 

 the water is no longer firmly bound, and the polypeptide chains 

 can come close up against one another to form microscopically 

 visible strands, while microscopically visible spaces are formed 

 between one such strand and another. A network of strands is thus 

 formed. If globular proteins are present, these will extend on 

 denaturation and participate in the formation of the strands. 



It may be said in brief summary that fixation by denaturing 

 renders globular proteins fibrous; irreversibly alters the relations 

 of all proteins with water, so that this is no longer firmly held; and 

 greatly increases the reactivity of certain side-groups of the 

 constituent amino-acids, so that they respond much more readily 

 to tests for their presence and attach themselves freely to dyes ; but 

 the specificity of many proteins is lost. The chemical denaturing 

 agents are non-additive: they achieve their effects while remaining 

 essentially detached. 



Many fixatives are additive to proteins. The difference between 

 additive and non-additive fixation is not quite so great as might 

 be supposed. Most substances undergo a profound change if an 

 atom be added to them, but proteins are necessarily different in 

 this respect. A fixative might be capable of adding itself to the 

 side-group of a particular amino-acid that was very scantily 

 represented in a particular protein; the fixative might nevertheless 

 denature the protein as a whole. For this reason one must not 

 draw too sharp a distinction between denaturation by non- 

 additive fixatives and the changes brought about by additive ones. 

 The distinction is partly a matter of the arbitrary use of words. 

 Many of the changes described in the preceding part of this chap- 

 ter occur also when certain additive fixatives react with proteins. 



Nevertheless, a valid distinction does exist in most cases. 

 Further, certain additive fixatives, unlike any non-additive ones, 

 are non-coagulant of albumin. The familiar additive fixatives may 

 be grouped thus: — 



coagulant non-coagulant 



mercuric chloride formaldehyde 



chromium trioxide osmium tetroxide 



picric acid 



