THIAMINE 697 



it has no vitamin action on rats, 49 and in doses of 25 to 50 y per day it is 

 fatally toxic to young mice maintained on a low vitamin Bi diet supple- 



ci- 



n— CH 2 N+ C— CH 3 



CH 3 — L JLOH HC C— CH 2 CH 2 OH 



V 



oxythiamine 



mented with 1 y of thiamine per day. 74 The 5-/?-chloroethyl and 5-/3- 

 bromoethyl analogues of oxythiamine were not toxic, even when admin- 

 istered in doses as high as 100 y per day. More recently, it was reported 

 that a low-thiamine diet provided some protection for mice against 

 infection with the Lansing strain of poliomyelitis virus. Similar protec- 

 tion, though less marked, was afforded by the administration of oxythia- 

 mine. 75 



In 1945, Emerson and Southwick 84 demonstrated that the administra- 

 tion of the 2'-butyl homologue of thiamine to rats maintained on a sub- 

 optimal intake of thiamine produced polyneuritis and subnormal growth, 

 both characteristic of thiamine deficiency. This effect was counteracted 



N^^— CH 2 N+ C— CH 3 



C 4 H,JL. J-NH 2 HC C-CH 2 CH 2 OH 



N \/ 



S 



butylthiamine 



by increasing the thiamine intake; the inhibition index was approx- 

 imately 20. 



Ochoa and Peters 80 reported that thiamine, as well as a number of 

 pyrimidine analogues, stimulated the carboxylase system of yeast which 

 had been washed with an alkaline phosphate buffer solution. Westen- 

 brink, et al. sl showed that this apparent "stimulation" was actually due 

 to the fact that these compounds inhibited the dephosphorylation of the 

 cocarboxylase by a phosphatase present in the yeast. From the results 

 which are summarized in Table 46, it is evident that the inhibitory effect 

 depends on the presence of the 4-aminopyrimidine group. Weil-Malherbe 

 demonstrated that the presence of excess thiamine also slightly inhibits 

 the synthesis of cocarboxylase by yeast. 81a 



Weswig, Freed and Haag 85 reported that rats placed on diets contain- 

 ing bracken fern which had been air-dried and ground developed symp- 



