580 



B. K. FORSCHER AND D. V. COHN 



There is an important relationship between the relative magnitude 

 of the increase in C^^02 and the position of the label in the glucose 

 molecule. It shows that we are dealing with a specific metabolic 

 alteration rather than a generalized increase in cellular metabolic 

 activity or an increase in the number of metabolizing cells. Increased 

 production of CO2 can also be demonstrated with pvruvate-2-C^^ 

 as the substrate (Cohn and Forscher, 1961). 



The differential effect shown in Table I could be the result of one 

 of two possible types of alteration. The data would be consistent 

 with ( 1 ) an increased flow of metabolites through the Embden- 

 Meyerhof and the Krebs pathways with no change in the rate of 

 operation of the hexose monophosphate shunt, or with (2) an in- 

 creased rate of operation of some pathway involving preferential 

 oxidation of the 6-carbon of glucose. When incubations are carried 

 out in the presence of fluoroacetate, as shown in Table II, the in- 



TABLE II. Effect of Fluoroacetate on Metabolism in Bone 



" Fach flask contained 10 Mmoles glucose, labeled with 2 X 10'' cpm ghicose-6-C'S in 

 9.5 ml of Ivrebs bicarbonate buffer. 



' Fluoroacetate, 50 ^moles added to solution of substrate. 



creased CO2 production due to pretreatment with parathyroid hor- 

 mone disappears, indicating that the extra CO2 from C-6 of glucose 

 originates in the Krebs cycle. This observation correlates with that 

 of Raisz and co-workers ( 1961 ) that in the presence of fluoroacetate 

 there was decreased mobilization of calcium into the medium despite 

 an increased accumulation of citrate. They also found that iodoace- 

 tate decreased the mobilization of calcium, in agreement with 

 Schartum and Nichols (1961). Thus the metabolic activity respon- 



