The emerging physiological roles of the glycerophosphodiesterase family.

The glycerophosphodiester phosphodiesterases are evolutionarily conserved proteins that have been linked to several patho/physiological functions, comprising bacterial pathogenicity and mammalian cell proliferation or differentiation. The bacterial enzymes do not show preferential substrate selectivities among the glycerophosphodiesters, and they are mainly dedicated to glycerophosphodiester hydrolysis, producing glycerophosphate and alcohols as the building blocks that are required for bacterial biosynthetic pathways. In some cases, this enzymatic activity has been demonstrated to contribute to bacterial pathogenicity, such as with Hemophilus influenzae. Mammalian glyerophosphodiesterases have high substrate specificities, even if the number of potential physiological substrates is continuously increasing. Some of these mammalian enzymes have been directly linked to cell differentiation, such as GDE2, which triggers motor neuron differentiation, and GDE3, the enzymatic activity of which is necessary and sufficient to induce osteoblast differentiation. Instead, GDE5 has been shown to inhibit skeletal muscle development independent of its enzymatic activity.