MULTIPLE ENZYME SYSTEMS 



only as a means of providing the electron acceptors. Essentially 

 this is true in the MES, but in addition a failure of the coupled 

 system may result in a failure of the entire reaction chain. More 

 than this is concerned. 



In order to pursue the problem further let us look at a 

 MES outlined perhaps in an oversimplified manner in the scheme 

 on the preceding page. 



Here A, B, O, K, and R are beginning substrates or are 

 introduced into the chain along the main synthetic pathway, A, 

 C, F, J, P. The pathway O— ^P— >E represents the activation of 

 a normal metabolite to a derivative compound. GH2 — G is an 

 oxidation-reduction carrier system which is reoxidized by sub- 

 strate R. Y represents a side product. From this figure it will 

 be apparent that reaction (5), which reoxidizes the carrier sys- 

 tem GH2;=± G, could be a key mechanism. If reactions (1), (2), 

 (3), (4) proceed at rates such that none of the intermediate com- 

 pounds accumulate at more than trace levels, it follows that 

 each of the substrates of the respective enzymes catalyzing these 

 reactions may be present at a different level of saturation 

 (see Dixon (7)). The system is in a steady state and each sub- 

 strate is present at constant and low concentration. The mo- 

 ment that the rate of reaction (5) decreases below a critical level, 

 the sequence of reactions (1) to (4) is disturbed. F may ac- 

 cumulate and J and P decrease. The system reaches a new 

 steady state. This idea has been carefully explored by Chance 

 (4). If the reactions (1) to (4) are reversible, the reactants may 

 reach new levels. The coupled reaction then maintains the 

 MES in a steady state, keeping the substrates below saturation 

 levels. 



On the Role of the Michaelis Constant in Multiple Systems 



It is possible that differences in activities of certain enzymes 

 in a MES, i.e., enzyme-limiting steps, may in fact be derived 

 from variations in the dissociation constants of the intermediate 

 compounds with the various enzymes involved. 



545 



