[Liver aldolase as a possible target for the action of N-methyl-N-nitrosourea].
The effect of N-methyl-N-nitrosourea (MNU) on the activity of cytoplasmic and reversibly bound to subcellular structures liver aldolase was studied. In vitro, the activity of aldolase purified from rabbit muscles is inhibited by MNU by 70-80% relative to fructose-1,6-diphosphate and by 50-60% relative to fructose-1-phosphate. These substrates and the competitive inhibitor ATP do not protect the enzyme against the inactivation by MNU. MNU inhibits the activity of cytoplasmic aldolase by 30-40% and 20% 2-24 hours after a single injection (80 mg/kg) in vivo. The enzyme affinity for fructose-1,6-diphosphate is markedly decreased (2-fold). Activation of cytoplasmic aldolase relative to both substrates, which is especially well-pronounced with fructose-1-phosphate after inhibition of the enzyme activity, was observed. The enzyme activity relative to both substrates was found to increase in the mitochondrial and nuclear fractions within 48 hours. MNU has no effect on the activity of aldolase bound to microsomes. MNU influences the aldolase binding to organelle membranes. MNU injections at early periods (2-168 hours) accounts for the differences in the kinetic properties of cytoplasmic and reversibly bound to subcellular structures liver aldolase. These changes persist within 168 hours after MNU administration and may result in disturbances in cell metabolism as well as in the regulation of metabolic pathways, such as glycolysis and gluconeogenesis.
Treshchenkova
Iu A
IuA
Burlakova
E B
EB
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D003593:Cytoplasm / Q000201:enzymology; D005634:Fructose-Bisphosphate Aldolase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D008770:Methylnitrosourea / Q000494:pharmacology*; D051379:Mice; D008809:Mice, Inbred C3H; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D009132:Muscles / Q000201:enzymology; D011817:Rabbits
D008770:Methylnitrosourea; D005634:Fructose-Bisphosphate Aldolase
Al'dolaza pecheni kak vozmozhnaia mishen' deĭstviia nitrozometilmocheviny.