CHEMICAL PATHWAYS 123 



(b) Bisulphide Bridges 



Most of the proteins the primary structure of which has been unravelled 

 contain cystine. The disulphide bridges maintain a certain folding of the 

 polypeptide upon itseh' as in ribonuclease or they connect together different 

 polypeptide chains as in insulin. Disulphide bridges are essential to the 

 stability of the protein and to its physiological properties. It is not known 

 whether the formation of the SS bridges requires a specific enzymic 

 oxidation, or not; the oxidoreduction state of the — SH groups of proteins 

 and its relations, in the different regions of the cell, with free — SH con- 

 taining substances like glutathione are very obscure, a few steps in the 

 analysis of these interactions have only been made recently. 



(c) Association of Polypeptides 



Certain proteins are made of several polypeptide chains, either different 

 or identical, and the physiological properties of these proteins depend on 

 the association of the parts. Globin is a good example : each molecule is 

 made of four polypeptides: two a chains, two /S chains, assembled in an 

 intricate structure (Perutz et al., 1960). The association of the a and ^ 

 chains into the finished protein occurs spontaneously in vitro under 

 adequate conditions. The formation of an active enzyme by mixing extracts 

 of two different mutants strains of Neurospora in the cold (see p. 18) is best 

 explained by the spontaneous association of polypeptides into active 

 enzyme. A related phenomenon is the association of two proteins into an 

 active enzyme (Yanofsky and Crawford, 1959). Again the correct associa- 

 tion arises spontaneously. 



(d) Further Tra?isformations 



Further changes occur in certain protein molecules, which transform 

 them into other proteins with quite different properties, as for instance the 

 transformation of a zymogen into active enzyme. It is a matter of taste to 

 consider these transformations as finishing stages of the synthesis of 

 certain proteins or as modifications undergone by finished proteins. We 

 will here adopt the latter attitude, because these further changes do not 

 concern all protein molecules. The transformations result from the action 

 of specific enzymes; they are of various types and each would deserve 

 special study; a few examples will simply be quoted here. Thus trans- 

 formations of pepsinogen, trypsinogen or chymotrypsinogen into the cor- 

 responding enzymes are interesting cases of limited proteolysis ; so is the 

 cascade of protein transformations involved in blood clotting. Phosphory- 

 lase-fl results from the phosphorylation of four serine residues of phos- 

 phorylase-6 (Fischer et al, 1959), followed by dimerization (Keller and 

 Cori, 1953; Krebs and Fischer, 1956). Collagen and certain plant proteins 

 contain hydroxyproline. At variance with the twenty common amino acids, 



