In vivo actions of bestatin-related compounds in relation to their actions in vitro.

A study was performed to elucidate the effects of low-molecular-weight enzyme inhibitors on enzyme networks in vivo. Seven compounds, including bestatin and its 5 derivatives and arphamenine B, were tested, with each of them being administered to mice at the dose of 200 micrograms/day for 8 consecutive days. The spectrum of enzymatic changes thus induced were extensive and were not simply explainable by the in vitro actions of each agent administered. Nevertheless, a multivariate study on the changes in enzyme networks showed some degree of interrelationship between the in vitro and in vivo actions of the agents under study. The present findings seem to certify that the direct enzyme-inhibiting effect motivates the extensive movement of enzyme networks in vivo, although the latter often seems rather paradoxical at a glance.