Evolution of enzymatic regulation of prostaglandin action: novel connections to regulation of human sex and adrenal function, antibiotic synthesis and nitrogen fixation

Abstract

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 C15 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.