In vivo inhibition of aspartate aminotransferase in mice by L-hydrazinosuccinate.
L-Hydrazinosuccinate, which has been shown to be a slow-, tight-binding inhibitor of aspartate aminotransferase (EC 2.6.1.1) in vitro, was tested as an inhibitor in vivo of the enzyme as well as other pyridoxal enzymes. Intraperitoneal administration to mice at a dose of 0.6 mmol/kg rapidly decreased aspartate aminotransferase activities in liver and kidney cytosols to a minimal level lower than 10% of the original, and no appreciable reversal of the inhibition was observed after 24 h; at lower doses the activities were significantly recovered during the same period following an initial marked decrease. Of the other pyridoxal enzymes tested, alanine aminotransferase in liver was the most sensitive to the inhibitor. It was initially inhibited as severely as aspartate aminotransferase, but the inhibition was reversed considerably faster. Aspartate aminotransferase activities in brain and heart were less severely affected than those in liver and kidney; they were less markedly lowered initially and were substantially recovered after 24 h. Consistent with the observed organ specificity, heated extracts from brain and heart in the mice administered with the inhibitor showed relatively weak inhibitory activities in vitro to aspartate aminotransferase purified from pig heart, while the extracts from liver and kidney were strongly inhibitory.
D000818:Animals; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006834:Hydrazines / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D051379:Mice; D013386:Succinates
D006834:Hydrazines; D013386:Succinates; D001224:Aspartic Acid; C042747:hydrazinosuccinic acid; D001219:Aspartate Aminotransferases