Inhibition of CMP-N-acetylneuraminic acid:lactosylceramide sialyltransferase by nucleotides, nucleotide sugars and nucleotide dialdehydes.
The effects of nucleotides, nucleotide sugars and nucleotide dialdehydes on the activity and kinetics of cytidine 5'-monophospho-N-acetylneuraminic acid:lactosylceramide (alpha 2-->3) sialyltransferase (SAT-1) in microsomes derived from embryonic chick brain were investigated. Although under physiological conditions this enzyme utilizes a CMP-sugar as substrate, it was found that UDP-dialdehyde was an effective inhibitor of SAT-1 activity. CMP-dialdehyde was only slightly more efficient at inhibiting SAT-1 activity. Similar findings were found for the inhibitory effects of UDP versus CMP. In addition, two UDP-sugars (UDP-Gal and UDP-GalNAc) were also slightly inhibitory. Kinetic analyses demonstrate that both UDP- and CMP-dialdehydes are competitive inhibitors of SAT-1 activity. The data suggests that the substrate specificity of microsomal SAT-1 resides more in the sugar moiety, rather than in the nucleotide portion of the substrate.
Department of Anatomical Sciences and Neurobiology, School of Medicine, University of Louisville, KY 40292.
L D
LD
Cambron
K C
KC
Leskawa
D000818:Animals; D001921:Brain / Q000201:enzymology*; D002642:Chick Embryo; D003568:Cytidine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D008861:Microsomes / Q000201:enzymology*; D012265:Ribonucleotides / Q000494:pharmacology*; D012799:Sialyltransferases / Q000037:antagonists & inhibitors*; D014530:Uridine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D014531:Uridine Diphosphate Galactose / Q000494:pharmacology; D014536:Uridine Diphosphate N-Acetylgalactosamine / Q000494:pharmacology; D014539:Uridine Diphosphate Sugars / Q000494:pharmacology*
D012265:Ribonucleotides; D014539:Uridine Diphosphate Sugars; D014531:Uridine Diphosphate Galactose; D014530:Uridine Diphosphate; C033179:UDP dialdehyde; C081622:cytidine monophosphate dialdehyde; D014536:Uridine Diphosphate N-Acetylgalactosamine; D012799:Sialyltransferases; C021343:haematoside synthetase; D003568:Cytidine Monophosphate