Reaction mechanism of prostaglandin E2 biosynthesis and its modeling

The reaction mechanism of PGE₂ biosynthesis was investigated by a detailed examination of the cyclo-oxygenase and PGE₂-isomerase activities in acetone-pentane powder (microsomal fraction of ram seminal vesicular glands). Two main types of inactivating process were recognized in the reaction system. One type was due to irreversible inactivation caused by the oxidizing agent [O]^·_X released through the reduction of PGG₂ to PGH₂, while the other type was due to reversible inhibition which was supposed to be derived from the precursor arachidonic acid (AA). This inhibitor was found to block the activities of both cyclooxygenase and PGE₂-isomerase, and to compete with the substrates AA and PGH₂. Although no significant substrate inhibition was observed, arachidonic acid was slightly inhibitory toward PGE₂-isomerase.