An Inhibitor of Glucosylceramide Synthase Inhibits the Human Enzyme, but Not Enzymes from Other Organisms

Abstract

Specific inhibitors of glucosylceramide biosynthesis are used as drugs for the treatment of some human diseases correlated to glycosphingolipid metabolism. The target of the presently available inhibitors is the human glucosylceramide synthase (GCS), but effects on enzymes from other organisms have not been studied. We expressed cDNAs encoding GCS enzymes from lower animals, plants, fungi, and bacteria in the yeast P. pastoris. In vitro GCS assays with the GCS inhibitor D-threo-1-(3′,4′-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol showed that this inhibitor did not affect non-human GCS enzymes.

• glucosylceramide synthase (GCS)
• glycosphingolipids
• D-threo-1-(3′,4′-ethylenedioxy)phenyl-2-palmitoylamino-3-pyrrolidino-1-propanol (ethylenedioxy-P4)