Prostaglandin H synthase as a limiting enzyme of prostaglandin synthesis: substrate-induced inactivation as a new kind of enzyme activity regulation.

Abstract

The properties of prostaglandin H synthase (PGHS) as a protein and as a rate-limiting enzyme of physiologically active prostanoid synthesis have been considered. Fast and dramatic changes in the protein structure were shown to accompany inactivation of PGHS in the course of the reaction. The conclusions derived from the study of the steady-state kinetics of the enzyme action are discussed, and a minimal kinetic scheme is proposed. The mechanism of substrate-induced inactivation of PGHS is suggested as a basis for the regulation at the prostanoid level. The mechanism is hypothesized to be a new regulatory mechanism of enzyme activity in biological systems.