180 ASPECTS OF BIOCHEMICAL EFFECTS 



lutions, that is for a very wide range of concentrations, the effect of 

 competitive recombination is so neghgible that the ionic yield is constant. 

 Beyond 15 per cent the direct action would become noticeable. A fur- 

 ther characteristic of the indirect action on complex organic substances 

 is the exponential curve obtained when the ratio of the concentration 

 of biologically active material remaining after irradiation, to the initial 

 concentration, is plotted against the radiation dose. This is due to the 

 ever-growing competition for radicals by the increasing fraction of al- 

 ready inactivated solute. In fact this competition is a manifestation of 

 the so-called protection effect, that is the sharing of radicals by two or 

 more solutes which takes place according to the relative concentrations 

 and abilities of these solutes to react with radicals, thus leading to a 

 mutual reduction of the radiation effect. Last but not least, evidence 

 is accumulating that the indirect action can be very pH dependent. 

 These relationships have been established for a number of biologically 

 active substances, for example enzymes, viruses, and toxins. It is, how- 

 ever, justified to focus attention in the first place on enzymes which 

 occur in an abundance of varieties within cells but individually in minute 

 amounts. Their importance lies in the fact that no meta- or anabolic 

 change can take place without their help. At the same time they are 

 substances which allow of quantitative determination of radiation effects. 

 Furthermore, enzymes are, apart from their prosthetic groups, proteins, 

 and results obtained with them are one aspect of the response to radi- 

 ation of molecules of high molecular weight and intricate composition. 



Inactivation of Enzymes 



What is actually measured in such experiments is only the deactiva- 

 tion of the enzymatic activity, generally without reference to the chemi- 

 cal reaction underlying this. There have been, however, two attempts 

 to define more precisely the process of inactivation. One is the exten- 

 sive work done on the class of so-called SH — enzymes (7). In this par- 

 ticular class some of the sulfhydryl groups of the protein are essential 

 for enzymatic activity, and it could be shown that these were oxidized 

 by radiation and thereby inactivated, unless they were shielded against 

 radiation by linkage to SH — • reagents. Sometimes it was possible to 

 restore the enzymatic activity fully by subsequent addition of a fresh 

 supply of SH — groups in the form of glutathione. Barron and his col- 

 laborators have been prominent in this line of research. 



The other attempt has been an investigation with the enzyme d-amino 

 acid oxidase, which can be split into two essential components, the pros- 

 thetic group alloxazine adenine dinucleotide and the specific protein (8). 



