586 B. K. FORSCIIF^R AND D. V. COIIN 



tabolites through the pyruvic acid-oxidase complex to acetyl coen- 

 zyme A and through the condensing system or "citrogenase." Excess 

 parathyroid hormone increases the flow through this bottleneck 

 ( Table VI ) . This opening of a bottleneck is suggested not only by 



TABLE VI. Summary" of Effect of Parathyroid Extract 

 ON Production of C"02 by Bone 



° Taken from different experiments with slightly different experimental conditions. 

 However, for each substrate, conditions were identical for tissues derived from control 

 animals and from animals treated with paratnyroid extract. 



increased amounts of C'^02 from C^ ^-labeled precursors before the 

 bottleneck, but also by the decreased amounts of C^^02 from pre- 

 cursors after the bottleneck, which decrease presumably results from 

 dilution secondary to increased flow. There is no real accumulation 

 of metabolic citrate, since the reactions of the Krebs cycle follow in 

 sequence. If more citrate is produced in the cell, more is oxodized. 

 The real consequence of increasing the flow through the bottleneck 

 is a greater production of CO2. 



We do not yet haye sufficient data to establish clearly which of 

 the two enzyme systems between pyruvate and citrate is the actual 

 controlling factor. At this time we might tentatively postulate that 

 the crucial point in the sequence, and the site of hormone action, 

 is in the pyruvic acid-oxidase complex. This suggestion derives from 

 the fact that lactate, which accumulates in large amounts, is the 

 major end product. If the conversion of pyruvate to acetyl coenzyme 

 A proceeded rapidly, and the condensation to citrate were the limit- 

 ing reaction, acetate or some other derivative of acetyl coenzyme A 

 should be the accumulating end product. 



