Inhibition of CMP-N-Acetylneuraminic Acid: Lactosylceramide Sialyltransferase by Nucleotides, Nucleotide Sugars and Nucleotide Dialdehydes

• Published in: Biochemical and biophysical research communications Vol. 193; no. 2; pp. 585 - 590
• Main Authors: Cambron, L.D., Leskawa, K.C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.06.1993
• Subjects: Animals; Brain - enzymology; Chick Embryo; Cytidine Monophosphate - analogs & derivatives; Cytidine Monophosphate - pharmacology; Kinetics; Microsomes - enzymology; Ribonucleotides - pharmacology; Sialyltransferases - antagonists & inhibitors; Uridine Diphosphate - analogs & derivatives; Uridine Diphosphate - pharmacology; Uridine Diphosphate Galactose - pharmacology; Uridine Diphosphate N-Acetylgalactosamine - pharmacology; Uridine Diphosphate Sugars - pharmacology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1993.1664

The effects of nucleotides, nucleotide sugars and nucleotide dialdehydes on the activity and kinetics of cytidine 5′-monophospho-N-acetylneuraminic acid : lactosylceramide (α2→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.