Ganglioside biosynthesis in rat liver: alteration of sialyltransferase activities by nucleotides.
CMP-NAcNeu:GM3 ganglioside sialyltransferase (GD3 synthase) was characterized with respect to regulation of activity by nucleotides and compared in this regard with other sialyltransferases of ganglioside biosynthesis. Nucleotides preferentially inhibited the activity of GD3 synthase. Di- and trinucleotides inhibited most strongly and cytidine nucleotides were the most inhibitory class. The mode of inhibition by CMP (competitive or noncompetitive) varied with storage conditions of Golgi apparatus membranes; CMP inhibition was decreased during a series of consecutive freeze-thawings of membranes. Also, GD3 synthase inhibition by CDP was only partially relieved by excess Mg2+. With lactosylceramide as the in vitro precursor, synthesis of GM3 was always less inhibited by cytidine nucleotides than was that of GD3 and GT3. An 8-fold reduction in the ratio GD3/GM3 in the reaction products was obtained at 1.5 mM CTP. Separate incubations for the sialylation of GM3 or GM1 showed cytidine nucleotides increased synthesis of GD1a relative to GD3 by 3.5-fold.
D000818:Animals; D003565:Cytidine Diphosphate / Q000494:pharmacology*; D003568:Cytidine Monophosphate / Q000494:pharmacology*; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; D003570:Cytidine Triphosphate / Q000494:pharmacology*; D003597:Cytosine Nucleotides / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D006056:Golgi Apparatus / Q000201:enzymology*; D008099:Liver / Q000201:enzymology; D008274:Magnesium / Q000494:pharmacology; D051381:Rats; D012799:Sialyltransferases / Q000378:metabolism*; D014166:Transferases / Q000378:metabolism*
D003597:Cytosine Nucleotides; D003569:Cytidine Monophosphate N-Acetylneuraminic Acid; D003565:Cytidine Diphosphate; D003570:Cytidine Triphosphate; D014166:Transferases; D012799:Sialyltransferases; D003568:Cytidine Monophosphate; D008274:Magnesium