The phosphorylated form of succinyl coenzyme A synthetase (E-P) is shown by rapid mixing and quenching experiments to participate on the major or exclusive catalytic pathway. The initial rate of appearance of E-P is as least as great as the initial steady-state rate of the over-all reaction in either direction and, in the direction of adenosine triphosphate synthesis, the steady-state level of E-P appears to be reached before the establishment of the steady-state rate of adenosine triphosphate formation. Succinyl coenzyme A synthetase provides an excellent example of a phenomenon termed substrate synergism. This refers to acceleration by a substrate or substrates of a reaction undergone by other substrates of a multisubstrate enzyme. Theoretical considerations show that such synergism can be conclusively detected by appropriate comparison of rates of isotopic exchange between certain substrates in the presence or absence of other substrates. Substrate synergism occurs with succinyl coenzyme A synthetase as measured by the adenosine diphosphate adenosine triphosphate, succinate ⇄ succinyl coenzyme A, and E-P adenosine triphosphate exchange reactions. Acceleration of the adenosine diphosphate adenosine triphosphate exchange by succinyl coenzyme A or by all other substrates likely reflects modifications important in net catalysis because both the exchange and over-all reaction probably involve E-P as an intermediate. © 1968, American Chemical Society. All rights reserved.
