HENRY R. MAHLER 



together again by means of nonporphyrin metal chelates to form 

 even larger units such as the "native" DPNH oxidase. 



IMPLICATION OF METALS IN OXIDATIVE PHOSPHORYLATION 



The finding that metals are involved in electron transport 

 has given rise to different speculations as to how these cationic 

 constituents might be the locus of primary phosphate bond 

 formation during electron transport. A possible mechanism 

 might envisage the uptake of phosphate during the reduction 

 of the metal in the course of the catalytic cycle (28). This 

 reduced phospho-metal-enzyme complex might be more stable 

 thermodynamically with respect to hydrolysis than the corre- 

 sponding oxidized complex. If, ( 7) the difference in the free 

 energy of hydrolysis of the two complexes were of the order of 

 — 10,000 cal.* and (2) some mechanism for the transfer of this 

 metal bound phosphate to yield eventually a nucleotide pyro- 

 phosphate were available, then this process would constitute 

 oxidative phosphorylation. The cycle reduction -^ phosphate 

 uptake -^ oxidation — > phosphate release is believed to be 

 obligatory in the case of the molybdoflavoproteins, but there 

 phosphate release by hydrolysis is so rapid that a search for 

 phosphate transfer is probably doomed to failure. The isolated 

 DPNH-cytochrome reductase, on the other hand, does appear 

 capable of phosphate uptake during catalysis, without rapid 

 hydrolysis of the phosphate, but no mechanism for phosphate 

 transfer has so far been discovered and thus this phosphate uptake 

 does not lead to oxidative phosphorylation but only to phosphate 

 inhibition of the enzyme. It is, however, conceivable that a 

 search for a system capable both of an uptake of phosphate to 

 form a metal phosphate during catalysis and of phosphate 



* This assumption at least in the case of iron would not appear to be 

 unreasonable by analogy with the known properties of the corresponding 

 inorganic iron compounds (4). Thus the formation constant of the ferric 

 hydroxy complex is considerably higher than that of the ferrous complex, 

 whereas the solubility of ferric phosphate is higher than that of ferrous phos- 

 phate. 



266 



