Inhibition of the biosynthesis of N-acetylneuraminic acid by metal ions and selenium in vitro.
In liver homogenate the biosynthesis of N-acetylneuraminic acid using N-acetylglucosamine as precursor can be followed stepwise by applying different chromatographic procedures. In this cell-free system 16 metal ions (Zn2+, Mn2+, La3+, Co2+, Cu2+, Hg2+, VO3-, Pb2+, Ce3+, Cd2+, Fe2+, Fe3+, Al3+, Sn2+, Cs+ and Li+) and the selenium compounds, selenium(IV) oxide and sodium selenite, have been checked with respect to their ability to influence a single or possibly several steps of the biosynthesis of N-acetylneuraminic acid. It could be shown that the following enzymes are sensitive to these metal ions (usually applied at a concentration of 1 mmol l-1): N-acetylglucosamine kinase (inhibited by Zn2+ and vandate), UDP-N-acetylglucosamine-2'-epimerase (inhibited by Zn2+, Co2+, Cu2+, Hg2+, VO3-, Pb2+, Cd2+, Fe3+, Cs+, Li+, selenium(IV) oxide and selenite), and N-acetylmannosamine kinase (inhibited by Zn2+, Cu2+, Cd2+ and Co2+). Dose dependent measurements have shown that Zn2+, Cu2+ and selenite are more efficient inhibitors of UDP-N-acetylglucosamine-2'-epimerase than vanadate. As for the N-acetylmannosamine kinase inhibition, a decreasing inhibitory effect exists in the following order Zn2+, Cd2+, Co2+ and Cu2+. In contrast, La3+, Al3+ and Mn2+ (1 mmol l-1) did not interfere with the biosynthesis of N-acetylneuraminic acid. Thus, the conclusion that the inhibitory effect of the metal ions investigated cannot be regarded as simply unspecific is justified.
Zeitler
R
R
Institut für Molekularbiologie und Biochemie, Freie Universität Berlin, Dahlem, Germany.
Banzer
J P
JP
Bauer
C
C
Reutter
W
W
D000117:Acetylglucosamine / Q000378:metabolism; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006595:Hexosamines / Q000378:metabolism; D008670:Metals / Q000494:pharmacology*; D019158:N-Acetylneuraminic Acid; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012643:Selenium / Q000494:pharmacology*; D012794:Sialic Acids / Q000096:biosynthesis*; D013438:Sulfhydryl Compounds / Q000494:pharmacology; D014537:Uridine Diphosphate N-Acetylglucosamine / Q000378:metabolism
D004791:Enzyme Inhibitors; D006595:Hexosamines; D008670:Metals; D011498:Protein Precursors; D012794:Sialic Acids; D013438:Sulfhydryl Compounds; D014537:Uridine Diphosphate N-Acetylglucosamine; D019158:N-Acetylneuraminic Acid; D012643:Selenium; D000117:Acetylglucosamine; C002022:N-acetylmannosamine