Inhibition of trypsin and papain by sodium aurothiomalate mediated by exchange reactions.

Sodium aurothiomalate has been shown to participate in exchange reactions leading to the inhibition of trypsin; for this exchange to take place it was necessary to include in the test system a suitable thiol, such as N-acetyl-cysteine. Neither N-acetyl-cysteine nor aurothiomalate on their own had any inhibitory action on trypsin. The results indicate that aurothiomalate dissociates in the presence of a carrier to form thiosuccinate and gold. The gold is responsible for trypsin inhibition since independent experiments demonstrated that the total concentration of thiosuccinate was insufficient to cause the observed inhibition of trypsin. Bovine serum albumin was shown to act as a carrier in place of N-acetyl-cysteine. It is known that histidine in the active centre of trypsin binds heavy metal ions with consequent inhibition of the enzyme. In this study, imidazole was shown to act as a carrier for gold from aurothiomalate to trypsin resulting in inhibition. This inhibition by gold was reversed when higher concentrations of imidazole were added to the test system due to competition for the trypsin-bound gold by imidazole. Conversely, the thiol enzyme papain was re-activated in the presence of low concentrations of sodium aurothiomalate and inhibited by higher concentrations of this reagent in a biphasic manner. This observation will be discussed in relation to the dissociation of sodium aurothiomalate. These observations can also be explained in terms of exchange reactions involving thiols and free metal ions.