266 



HENRY LARDY 



Both oligomycin [i] and aurovertin strongly inhibit the exchange of '^^F- 

 with the phosphate of ATP and the exchange of ^^O between P^^04H = 

 and water. 



For purposes of discussion, these experimental results may be examined 

 in the context of the accepted, but hypothetical, reactions involved in fixing 

 and transferring phosphate. 



X - I + pi«04H= ^X - Pi«03= + P80H (i) 



X - Pi«03 + ADP= ^ XH + ATP= = (2) 



P«OH + H,0 ^ lOH + Hai^O (3) 



X -^ I represents a product whose formation required the energy 

 available from an oxidation-reduction reaction. Reactions 1+3 account 



<U 4 



ATP ase induced by uncoupling agents 



5xlO"^M 2,4-dinitrophenol 

 10 M tncyano amino propene 

 02 fig valinomycin 

 SxlO-'iM O ME triac 

 lO'^M Mg aged M^ 



/ig aurovertin 



I 



//g oligomycin 



Fig. I. 



for the exchange of ^^O between phosphate and water [3] ; reaction 2 

 accounts for exchange between ADP and ATP [4]. Reactions i +2 account 

 for ^'^Pj-ATP exchange [5]. Reaction 3 is assumed to be spontaneous. 



If we assume that reaction i is blocked by oligomycin and aurovertin, 

 we learn that DNP must act prior to the stage at which Pj enters the 

 sequence. If DNP prevents formation of X ~ I or catalyzes the hydrolysis 

 of X ~ I or some earlier intermediate, it would prevent the inhibition of 

 respiration by oligomycin and aurovertin. Likewise these antibiotics would 

 block the effect of DNP on ATP hydrolysis. 



But this scheme does not adequately explain the different effects of 



