PARATHYROID HORMONE AND RAT CALVARIA METABOLISM 595 



of pyruvate is most satisfactoriK' explained in terms of a competition 

 iDetween pyruvate and fiuoroacetate for coenzvme A, for it is well 

 known that if p\'ru\'ate and fiuoroacetate are present together, the 

 greater amount of carbon incorporated into the cvcle is derived from 

 the pyruvate. 



As a consequence of its inhibitor action upon aconitase, fiuoroace- 

 tate poisoning of a tissue with a functioning TCA cycle usually 

 results in the accumulation of citric acid. Because of the large quan- 

 tity of citric acid which is present in bone mineral, however, in- 

 creased citrate concentration in response to fiuoroacetate injection 

 in vivo has not been shown to occur (Beaulieu, 1953). In a closed 

 system in vitro, changes in citrate content are easily demonstrable. 



Analyses of the medium and tissue showed that glucose addition 

 did not increase citrate accumulation, whereas, as shown in Table 

 III, fumarate on the one hand and fiuoroacetate on the other, alone 



TABLE III. Thp: Effect of Fluoroacetate and Substrates 



ON Citrate" and Lactate Production 



(Bicarbonate medium; glucose 17 mu; fumarate 5 mM; fluoroacetate 5 mM; 



2-hour incubation; averages of 4 to 8 flasks) 



" Note that with ghicose only, citrate is actually utilized despite its appearance in 

 the medium. Because of ease of exchange of citrate between tissue and medium it is 

 necessary to analyze the system /'/( toto. 



or in combination, did bring about an increase in total citrate. Even 

 with fumarate and fluoroacetate present at the same time, the rate 

 of appearance of citric acid in the medium was very considerably 

 less ( 15 times ) than that of lactate. Lactic acid production was not 

 significantly affected by the various additions, except, of course, by 

 the addition of glucose. 



