Mechanism of Hydrolysis of Adenosine Triphosphate catalysed by Lobster Muscle

Abstract

In previous publications¹ evidence has been presented for the occurrence of displacement mechanisms in a wide variety of enzymatic reactions to which those of adenosine triphosphate are closely analogous. Assuming that the adenosine triphosphate reactions proceed by the same mechanisms, it can be deduced from the nature of the products that the adenosine triphosphate can undergo nucleophilic attack at any of its three phosphorus atoms. As examples, the Lohmann reaction with creatine² must involve attack at the terminal phosphorus atom, the coenzyme A reaction of Lipmann et al.³ must involve attack at the middle phosphorus atom and the Kornberg reaction with nicotinamide mononucleotide⁴ must involve attack at the innermost phosphorus atom. If the adenosine triphosphate is hydrolysed by an adenosine triphosphatase in ordinary water to adenosine diphosphate and inorganic phosphate, the pathway is not obvious, since attack at either the terminal phosphorus atom or the middle phosphorus atom would give the same products. This ambiguity can be avoided, however, by using H₂¹⁸O, in which case the alternatives are clearly distinguishable (cf. reaction 1). The study of the mechanism of adenosine triphosphate hydrolysis in muscle was therefore performed in a medium of H₂¹⁸O and the products were analysed for their content of oxygen-18.