594 



PETER MITCHELL 



Special characteristics of vectorial metabolism in anisotropic 



enzyme systems 



The studies that Dr. Moyle and I have recently been carrying out on 

 the specificity and general kinetics of the entry of " a-ketoglutarate "and 

 "succinate" into Micrococcus lysodeikticiis, and the comparison of these 

 characteristics with those of the a-ketoglutarate dehydrogenase, succinic 

 dehydrogenase, succinyl-coenzyme A kinosynthetase, and other enzymes 

 present in the plasma membrane complex ([19, 46], and extensive unpub- 

 lished observations) has led us to represent the entry mechanism by the 

 tentative scheme of Fig. 3. This scheme is in accord with all the experi- 

 mental facts at present available to us, but I must emphasize that it is 



Endoplasm 



c-ketoglutarate 

 dehydrogenase 



q;-KETOCLUTARATE - *■ 



SUCCINATE 



O'-KETOGLUTARATE 



C02-HH2 



(SUCCINYL^) 

 ADP + P 



ATP 



Succinyl CoA 

 kinosynthetase 



Fig. 3. Diagram of "succinate" and " 3^-ketoglutarate " translocation through 

 the membrane of Micrococcus lysodeikticiis. The dehydrogenases are depicted as 

 part of the plasma membrane, anchored to each other (and to other substrata not 

 drawn) by specific residual bonds. 



nevertheless tentative; for, when one considers how unequivocal the 

 interpretation of such observations can be made, or in other words, how 

 close a correspondence one would expect to find between the various 

 constants (Michaelis constants, inhibitor constants, pH characteristics, 

 temperature coefficients, etc.) measured on the one hand for the intact 

 membrane system and on the other hand for the isolated enzymes and 

 carriers, it is apparent that not only the kinetic "constants" but also the 

 apparent thermodynamic "constants" of the reactions can be profoundly 

 afl^ected by the anisotropic situation of the catalysts in the membrane. It 

 will, I think, be appropriate to conclude my paper with a brief discussion 

 of this aspect of translocation catalysis, for it has an important bearing on 

 any experiments designed to identify the catalysts of membrane transport 

 by comparing their kinetic and thermodynamic constants in situ in a 



