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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References
Bauer C, Kassuba B, Recktenwald L, et al. 1983 Sugar analogues as inhibitors of glycosylation. In: Popper H, Reutter W, Gudat F, Köttgen E, eds.Structural Carbohydrates in the Liver, Lancaster: MTP Press; 527–537.
Corfield AP, Schauer R. 1982 Metabolism of sialic acids. In: Schauer R, ed.Sialic Acids: Chemistry, Metabolism and Fuction: Cell Biology Monographs, Vol. 10. Wien: Springer Verlag; 195–251.
Craig PJ 1986Organometallic Compounds in the Environment. London: Longman.
Grünholz H-J, Harms E, Opetz M, Reutter W. 1981 Inhibition ofin vitro biosynthesis ofN-acetylneuraminic acid byN-acyl- andN-alkyl-2-amino-2-deoxyhexoses.Carbhydr Res 96, 259–270.
Hultsch E, Reutter W, Decker K. 1972 Conversion ofN-acteyl-d-glucosamine intoN-acetyl-neuraminic acid in a cell free system of rat liver.Biochim Biophys Acta 237, 132–140.
Lewin LM, Wei R. 1966 Microassay of thiamine and its phosphate esters after separation by paper chromatography.Anal Biochem 16, 29–35.
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. 1951 Protein measurements with the Folin phenol reagent.J Biol Chem 193, 265–275.
Paladini A, Leloir L. 1952 Studies on uridine-diphosphateglucose.Biochem J 51, 426–430.
Reutter W, Bauer C. 1986 Inhibitors of glycoprotein biosynthesis.Adv Enzyme Reg 24, 405–416.
Rhead W, Schrauzer G. 1974 The selenium catalyzed reduction of methylene blue by thiols.Bioinorg Chem 3, 225–242.
Riordan J, Vallee B. 1972 Reactions withN-ethylmaleinimide andp-mercuribenzoate.Methods Enzymol 25, 449–456.
Warren L, Felsenfeld H. 1962 The biosynthesis of sialic acids.J Biol Chem 237, 1421–1431.
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Dedicated to Professor Theodor Günther on the occasion of his 60th birthday
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Zeitler, R., Banzer, JP., Bauer, C. et al. Inhibition of the biosynthesis ofN-acetylneuraminic acid by metal ions and seleniumin vitro . Biometals 5, 103–109 (1992). https://doi.org/10.1007/BF01062221
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DOI: https://doi.org/10.1007/BF01062221