ANALOGS OF THIAMINE 



521 



Table 2-32 



Effects of Thiamine Deficiency and Thiamine Analogs 

 ON THE Oxidative Decarboxylation of Keto Acids in Mitochondria " 



° The analogs were administered to rats at oxythiamine/thiamine = 200, and 

 pyrithiamine/thiamine — 5, these doses producing polyneuritis in several days. The 

 figures give the changes observed in the oxidation of the substrates indicated in 

 mitochondrial suspensions. (From Gubler, 1961.) 



oxythiamine is reversed poorly. The most obvious explanation of this is 

 that pyrithiamine blocks the synthesis of thiamine-PP, so that the tissues 

 are primarily deficient in cocarboxylase, whereas oxythiamine may exert 

 its inhibition mainly by binding to pyruvate oxidase in the form of its 

 diphosphate ester. These problems wiU be discussed after further effects 

 of these analogs have been presented. 



Feeding pyrithiamine to pigeons leads to a 50% reduction in the p>Tuvate 

 decarboxylase activity in breast muscle, and this can be reversed by the 

 addition of thiamine-PP to the homogenates (Koedam et al., 1956). This is 

 accompanied by a marked reduction in the thiamine-PP content of muscle, 

 so that it was concluded that there is no essential difference between di- 

 etary thiamine deficiency and pjTithiamine feeding. Pyruvate dismutation 

 and acetoin formation in breast and heart muscle are likewise depressed 

 by pyrithiamine feeding (Koedam, 1958). A large single dose of pyrithia- 

 mine (2.5 mg) leads to a rapid inhibition of acetoin formation and even after 

 8 days the activity does not return to normal. 



The respiratory quotient of rats treated with pyrithiamine (5 mg/day 



