GLYCOSYLTRANSFERASES OF RAT BRAIN THAT MAKE CEREBROSIDES: SUBSTRATE SPECIFICITY, INHIBITORS, AND ABNORMAL PRODUCTS 1

Abstract

Brain homogenates from young rats were assayed for their ability to synthesize cerebrosides from radioactive UDP-galactose or UDP-glucose and ceramide. A comparison of galactose transfer with ceramides made from different 2-hydroxy acids showed that the shortest one tested (C 7 ) was by far the best acceptor, while the poorest contained 18 carbon atoms; longer fatty acids were better than CIS. Glucosyltransferase, on the other hand, showed rather little chain length specificity or discrimination against hydroxy acid ceramides. Synthetic compounds analogous in structure to ceramides were tested as inhibitors of the sugar transferases. Some were found to act as sugar acceptors themselves, particularly amides of DL-erythro-1- phenyl-2-amino-1,3-propanediol. Some amides were good inhibitors of glucosyltransferase, particularly decanoyl norephedrine, decanoyl threo-1-phenyl-2-amino-1,3-propanediol and decenoyl phenylalaninol. The secondary amine analogous to the first of these, N -decyl norephedrine, was also very effective. No strong inhibitors of galactosyl transferase were found, although octanoyl D-threo- p -nitrophenyla- minopropanediol showed promise (42% inhibition at 0.3 mM). Octanoyl phenylalaninol was nearly as good an inhibitor; the inhibition appeared only after a lag period. It is suggested that the glucosyltransferase inhibitors might he useful in therapy of Gaucher's disease, by reducing the degradative load normally falling on glucocerebrosidase.