EVOLUTION OF ENZYMATIC REGULATION OF PROSTAGLANDIN ACTION - NOVEL CONNECTIONS TO REGULATION OF HUMAN SEX AND ADRENAL-FUNCTION, ANTIBIOTIC-SYNTHESIS AND NITROGEN-FIXATION

The recent determination of the amino acid sequences of enzymes that metabolize prostaglandins and steroids has revealed interesting connections between some of these enzymes. Human placental 15-hydroxyprostaglandin dehydrogenase, which catalyzes the oxidation of the Cl5 alcohol on prostaglandins E2 and F2-alpha, is homologous to 11-beta-hydroxysteroid, 17-beta-hydroxysteroid, and 3-alpha,20-beta-hydroxysteroid dehydrogenases. That is, these four enzymes are derived from a common ancestor. Moreover, enzymes important in synthesis of antibiotics and proteins synthesized by soil bacteria that form nitrogen-fixing nodules in alfalfa and soybeans are homologous to 15-hydroxyprostaglandin dehydrogenase. These homologies provide important insights into the origins of intercellular communication that is mediated by prostaglandins, steroids, and fatty acids.