528 



2, ANALOGS OF ENZYME REACTION COMPONENTS 



TIME (DAYS) 



Fig. 2-18. Pyrithiaraine concentrations in rat tissues after intra- 

 peritoneal injection of 1 mg. (From Rindi and Perri, 1961.) 



Effects on the Growth of Microorganisms 



The degree of inhibition of various bacteria and fungi by pyrithiamine 

 has been related to the pattern of thiamine biosynthesis (Robbins, 1941; 

 Woolley and White, 1943 c). Sensitivity to pyrithiamine was correlated with 

 a requirement for intact thiamine, whereas those organisms able to syn- 

 thesize thiamine completely are poorly inhibited. If the organisms require 

 only part of the thiamine molecule, the growth depression by pyrithiamine 

 is intermediate. If pyrithiamine interferes with either the formation or 

 enzymic function of thiamine-PP, it would be difficult to understand how 

 the manner of obtaining thiamine could determine sensitivity to the analog. 

 However, another factor must be considered. It was shown that pyrithia- 

 mine-resistant organisms possess an enzyme capable of cleaving pyrithia- 

 mine, probably a thiaminase, while sensitive thiamine-requiring organisms 

 do not. At least part of the resistance might be attributed to the ability 

 of these organisms to inactivate the analog; the pyridine portion split from 

 pyrithiamine would not be inhibitory and the pyrimidine portion can ac- 



