Effects of the inhibitors of IMP dehydrogenase, tiazofurin and mycophenolic acid, on glycoprotein metabolism

摘要: The effects of the inhibitors IMP dehydrogenase, tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) and mycophenolic acid, on synthesis cellular glycoproteins were evaluated in Sarcoma 180 cells. Both acid decreased rate incorporation [2-3H]mannose [2-3H]fucose into acid-precipitable within 4 hr exposure; this inhibitory activity was concentration dependent occurred absence a significant effect labeled glucosamine leucine acid-insoluble material. Interference with utilization [3H]mannose for formation paralleled by an inhibition [3H] mannose their lipid-linked oligosaccharide precursors following treatment cytotoxic concentrations (100 microM) or (10 microM); these actions 3 exposure to agents, maximal reductions being observed at 12 hr. Under conditions, intracellular GTP levels reduced 80%, whereas ATP pools remained unaffected ant UTP markedly increased. Guanosine prevented reversed drug-induced decrease other metabolic Inhibition fucose oligosaccharides preceded decreases labeling respective guanosine nucleotide sugars followed sequentially alterations plasma membrane as detected both binding cell agglutination caused plant lectin, concanavalin A. findings that produce architecture are indicative lesions induced agents selectively depress guanine through dehydrogenase.