Inhibition of protein, glycoprotein, ribonucleic acid and deoxyribonucleic acid synthesis by d-glucosamine and other sugars in mouse leukemic cells L5178Y and selective inhibition in SV-3T3 compared with 3T3 cells

Abstract

d-Glucosamine inhibited DNA, RNA, protein and glycoprotein synthesis in L5178Y mouse leukemia cells at levels from 10–100 μmoles/ml. d-Glucosamine was the most inhibitory monosaccharide studied but other monosaccharides and derivatives at 100 μmoles/ml caused the following percent inhibition of protein synthesis: d-glucosamine, 95 %; UDP-glucose, 89 %; UDP- N-acetylglucosamine, 83 %; glucosamine 6-phosphate, 54 %; mannosamine 45 %; mannose, 45 %; galactose 24 %; galactosamine, 23 %; N-acetylneuraminic acid, 18 %; fructose, 17 %; N-acetylmannosamine, 13 %; N-acetyl-glucosamine, 10 %; glucose, 6 %; fucose, 5 %; N-acetylgalactosamine, 0 %; ribose, 0 %; arabinase, 0 %; and xylose, 0 %; similar results were found for DNA, RNA and glycoprotein synthesis. d-Glucosamine inhibited DNA, RNA, protein and glycoprotein synthesis to a much greater degree in SV-3T3 than in 3T3 cells. The 100 μmoles/ml of d-glucosamine caused the following decreases in μmoles of uridine nucleotides per 10 11 cells: UMP 66 to 28, UDP 55 to 31, and UTP 49 to 28 while increasing the UDP- N-acetylhexosamine pool from 48 to 102 μmoles per 10 11 cells. The inhibition of the synthesis of RNA, DNA protein and glycoprotein caused by the d-glucosamine could be reversed by the addition of uridine nucleotides at the correct concentration; uracil and uridine were ineffective. ATP and nucleotides other than uridine nucleotides were ineffective in reversing the d-glucosamine inhibition. The inhibition of macromolecular synthesis caused by d-mannose in the L5178Y cells could also be reversed by the simultaneous addition of correct concentrations of uridine nucleotides.