ANALOGS OF THIAMINE 525 



found the thiaminase from bracken {Pteridium aquilinum) to be very sen- 

 sitive to ABMT, 15-20% inhibition being given by 0.002 mM and almost 

 complete inhibition by 0.05 mM. The inhibition is probably basically com- 

 petitive since it proceeds faster in the absence of thiamine. As far as I know, 

 this interesting compound has not been tested in whole animals to deter- 

 mine if thiaminase inhibition can be achieved and how this will alter thia- 

 mine metabolism. 



Effects on Excretion and Tissue Levels of Thiamine 



If these analogs displace thiamine or thiamine-PP from the tissues in 

 any way, or inhibit the transport or metabolism of thiamine, an increased 

 urinary excretion of thiamine would be expected, and this has been found 

 to occur in rats given 50 //g oxythiamine (Frohman and Day, 1949). One 

 might also predict that tissue levels of thiamine or its diphosphate would 

 be reduced, and this has been demonstrated for both pyrithiamine and oxy- 

 thiamine in mice, pigeons, and rats. The depression of tissue thiamine-PP 

 seems to be generally associated with a rise in blood pyruvate, so that at 

 least part of this depletion is related to enzymes involved in the oxidation 

 or decarboxylation of a-keto acids. Inasmuch as theories for the mechan- 

 isms by which these analogs act depend on the changes in tissue thiamine 

 levels, it will be necessary to examine the results with some care. 



Pyrithiamine markedly depletes the tissues of thiamine-PP in pigeons. 

 Controls were fed 100 //g thiamine per day and another group was fed 623 //g 

 pyrithiamine each day in addition; after an average survival time of 19 days, 

 the thiamine-PP levels in the tissues were those shown in the following 

 tabulation (Koedam et al., 1956). The pyruvate decarboxylase activity in 

 muscle is reduced around 50% and adding thiamine-PP restores activity. 



Thiamine-PP content (/<g/g) 



Tissue 



Heart 



Brain 



Liver 



Breast muscle 



Kidney 



The fall in thiamine-PP level is quite rapid; at 4 days it is mainly complete 

 in most tissues, and from the data on pjTuvate utilization it would appear 

 that a marked decrease occurs within 1 day (Koedam, 1958). Pigeons given 

 a single large dose of pyrithiamine (10 mg) and examined 64 days later show 



