Citrulline accumulation in mice induced by administration of L-hydrazinosuccinate.
L-Hydrazinosuccinate has been shown to induce a marked inhibition of liver aspartate aminotransferase isoenzymes in mice. The effects of the drug on the amino acid content of liver were studied. Intraperitoneal administration of L-hydrazinosuccinate enormously increased the citrulline content of liver and plasma in 6 hr and, less markedly, increased the glutamate and ammonia content of liver with a simultaneous decrease in the aspartate content. Drug administration also induced a marked increase in the liver mitochondrial activity of citrulline formation from ornithine, ammonia and carbon dioxide, with a similar increase in N-acetylglutamate content; a prominent increase in liver tryptophan dioxygenase activity; and an elevated level of plasma corticosterone. The increase of citrulline was interpreted to be produced by decreased conversion of citrulline to argininosuccinate due to a lack of aspartate because of inhibition of aspartate aminotransferase by the drug and increased formation of citrulline due to increases of glutamate and ammonia, which further induced the increase of N-acetylglutamate, because of inhibition of aminotransferase as well as stimulation of amino acid degradation by glucocorticoids.
Department of Biochemistry, Kyoto Prefectural University of Medicine, Japan.
R H
RH
Yamada
Y
Y
Wakabayashi
A
A
Iwashima
T
T
Hasegawa
D000596:Amino Acids / Q000032:analysis; D000641:Ammonia / Q000378:metabolism; D000818:Animals; D001219:Aspartate Aminotransferases / Q000037:antagonists & inhibitors*; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002956:Citrulline / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D006834:Hydrazines / Q000494:pharmacology*; D008099:Liver / Q000032:analysis / Q000378:metabolism; D008297:Male; D051379:Mice; D013386:Succinates
D000596:Amino Acids; D006834:Hydrazines; D013386:Succinates; D002956:Citrulline; D001224:Aspartic Acid; D000641:Ammonia; C042747:hydrazinosuccinic acid; D001219:Aspartate Aminotransferases; D003345:Corticosterone