Citrulline accumulation in mice induced by administration of l-hydrazinosuccinate

Abstract

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 6hr 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.