452 2. ANALOGS OF ENZYME REACTION COMPONENTS 



had been postulated that sulfite must pass through thiosulfate to be utiliz- 

 ed, a shunt around thiosulfate was proposed: 



I I 



Active sulfate -> active sulfite -> active thiosulfate -► growth 



t t t 



sulfate sulfite thiosulfate 



Sulfate would thus block the formation of active thiosulfate from exogenous 

 thiosulfate, or it could block the utilization of active thiosulfate. Another 

 possibility is that thiosulfate transport into the cell is depressed by sulfate, 

 in which case there is no necessity to assume a shunt as above. 



SIMPLE ION ANTAGONISMS 



Many examples of the inhibition of biological, metabolic, or enzymic 

 processes by simple inorganic ions are known and in certain instances it is 

 likely that the mechanism involves a competition between the inhibiting 

 ion and a necessary ionic cofactor. The inhibiting ions may be considered 

 as analogs of the normally functional ions. It is impossible here to treat 

 this subject completely but it may be worthwhile to mention briefly some 

 specific examples of competitive enzyme inhibition to illustrate the phe- 

 nomenon. MacLeod and Snell (1950) emphasized the possible importance 

 of such competitions in the effects of certain ions on the growth of bacteria. 

 The growth of Lactobacillus arabinosus is suppressed by various ions and it 

 was concluded that some of these effects are due to the fact that the inhib- 

 itory ions are structural analogs of the metal ions which are cofactors in 

 metabolism. The following antagonisms, among others, were demonstrated: 

 K+ reverses the inhibitory effects of Na+ and NH4+; K+ reverses the in- 

 hibitory effects of Rb+; Zn++ reverses the inhibitory effects of Mn++; and 

 Mg++, Ca++, and Sr++ reverse the inhibitory effects of Zn++. Actually it is 

 not certain that these antagonisms relate to metabolic events, since it is 

 possible that physiological ions play nonmetabolic roles in bacteria, and it 

 would be interesting to investigate these antagonisms on a metabohc level. 

 Inasmuch as so many enzymes either involve ionic cofactors or are affected 

 by physiological ions, it is likely that such competitions are very common 

 and important in metabolic regulation. 



The phosphotransacetylase of Clostridium kluyveri is active only in the 

 presence of K+ or NH4+ ions. Inhibition is exerted by Na+ and Li+ ions, 

 and this can be overcome by increasing the K+ or NH4+ concentration, so 

 that competition for an enzyme site would seem likely (Stadtman, 1955). 

 Yeast acid phosphatase requires Mg++ and is inhibited by Ca++, the inhi- 

 bition being strictly competitive, as shown by double reciprocal plots (Tsuboi 

 and Hudson, 1956). Ba++ does not inhibit at all, but Mn++ and Zn++ depress 



