60 METABOLISM 



range of action, and catalysed tlie oxidative deamination of no less than eleven 

 amino-acids. 



Quastel (1926) and Quastel and Wooldridge (1927a, b) suggest that the activa- 

 tion of substrate molecules after their specific adsorption to the enzyme surface 

 is due to their polarization by electrical fields which characterize the " active 

 centres " of cellular and intracellular structures. The active centres are conceived 

 as being developed as the result of molecular strain or distortion of certain groups 

 or molecules brought about by the intermolecular or intramolecular forces that 

 determine the formation of large colloidal aggregates. 



As an alternative to the process of absorption and activation, Woolf (1931) 

 suggests that activation results from the distortion of the substrate molecule 

 which occurs when enzyme donators and acceptors combine at the enzymic surface. 

 Direct evidence of such a combination was produced by Stern (1936), who by 

 optical means was able to demonstrate the formation of an intermediate com- 

 pound, not merely an absorption complex, between substrate and enzyme, in 

 the decomposition of monoethyl hydrogen peroxide by animal liver catalase. 



Besides the configuration of the active groups on the surface of the enzymic 

 particle, their activity may also be determined by the spatial relationship of one 

 group with another. The oxygen uptake resulting from the action upon lactic 

 acid of the lactic dehydrogenase and the cytochrome-cytochrome oxidase system of 

 Bad. ccli is not increased if cytochrome c and cytochrome oxidase from heart muscle 

 are added to the mixture (Keilin and Harpley 1941), suggesting that the components 

 of the bacterial dehydrogenase system are intimately bound to the protein of a 

 single colloid particle, together with the native cytochrome system, to form a single 

 oxidizing system whose efficiency depends on the mutual accessibility of the 

 components. Succinic dehydrogenase and cytochrome oxidase (Potter 1941) and 

 co-enzyme I and cytochrome c reductase (Lockhart and Potter 1941) have been 

 found in similar association on particles produced by cell-disintegration. In other 

 words, the efficiency and, it might be added, the specificity, of an enzyme system 

 depends not only on the integrity of the components, but on their spatial distribution 

 in the cell containing them. The various cytochrome compounds, indeed, afford 

 an excellent example of the part the so-called " protein-carrier " plays in deter- 

 mining the nature of an enzyme. Recent work has shown that a common feature 

 of these compounds is an iron atom, held by some of its co-ordination valencies 

 to the pyrrol nuclei, forming a tetrapyrrol compound, while others attach this 

 tetrapyrrol compound to the protein. The activity of the resulting compound, 

 i.e. whether it behaves as a cytochrome, cytochrome oxidase, etc., is determined 

 by the nature of the protein. It follows that the distribution of these respiratory 

 pigments, for example, among the bacteria, will be conditioned more by the nature 

 of the proteins available for conjugation, than by the distribution of the pyrrolic 

 iron compounds (Keilin 1943). 



Certain observations by Penrose and Quastel (1930) are of interest from this 

 point of view. There is an organism {Micrococcus lysodeikticus) that is peculiarly 

 susceptible to lysis by an active substance (lysozyme), which is contained in various 

 tissues and secretions (see p. 1020). A suspension of this organism activates lactic 

 acid, glucose, Isevulose and glutamic acid, among other substances, as hydrogen 

 donators. After dissolution by lysozyme the bacteria are found to have lost 

 completely their power to activate the hexose sugars and glutamic acid, while 

 retaining some 30 per cent, of their activity against lactic acid. 



