N-acetylneuraminic acid biosynthesis
inhibition of enzymes
Springer Online Journal Archives 1860-2000
Chemistry and Pharmacology
Abstract In liver homogenate the biosynthesis ofN-acetylneuraminic acid usingN-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+, VO 3 − , 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 possible several steps of the biosynthesis ofN-acetylneuraminic acid. It could be shown that the following enzymes are sensitive to these metal ions (usually applied at a concentration of 1 mmoll−1):N-acetylglucosamine kinase (inhibited by Zn2+ and vandate), UDP-N-acetylglucosamine-2′-epimerase (inhibited by zn2+, Co2+, Cu2+, Hg2+, VO 3 − , Pb2+, Cd2+, Fe3+, Cs+, Li+, selenium(IV) oxide and selenite), andN-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 theN-acetylmannosamine kinase inhibition, a decreasing inhibitory effect exists in the following order Zn2+, Cd2+, Co2+ and Cu2+. In contrast, La3+, Al3+ and Mn2+ (1 mmoll−1) did not interfere with the biosynthesis ofN-acetylneuraminic acid. Thus, the conclusion that the inhibitory effect of the metal ions investigated cannot be regarded as simply unspecific is justified.
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