Enzymological studies on ammonium detoxication in liver:I. Measurement of the activities of urea cycle enzymes and the enzymes concerning with glutamic acid metabolism in liver after ammonium chloride administration

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It is well known that the urea cycle and the metabolic pathway of glutamic acid in liver are chiefly involved in detoxication of ammonium. Pathogenesis of hyperammoniaemia, however, has not been completely understood up to date, though overproduction of ammonium in the intestine, intra- or extrahepatic portosystemic shunt formations or impaired hepatic ammonium detoxication were considered to be important aetiologic factors.It is very interesting problem whether or not there is the adaptability on detoxication of ammonium in the damaged liver, in which continuous inflow of ammonium produced in the intestine exists.In order to investigate on this problem, the experimental hyperammoniaemia was provided by parenteral administration of ammonium chloride in control rats and the rats with damagedliver by carbon tetrachloride, and then the enzymes, including all members in urea cycle and two of them in the metabolic pathway of glutamic acid and also the intermediates produced in these metabolic pathways, were assayed.It was shown that the activities of arginase, ornithine transcarbamylase, arginine synthetase, glutamic dehydrogenase and glutamine synthetase were increased in control rats after the repeated parenteral administration of ammonium chloride, and plasma contents of citrulline and glutamic acid were remained at the levels prior to the treatments. Therefore, it was reasonable to presume that various enzymes of urea cycle and the pathway of glutamic acid metabolism would be increased through the induction under the condition of continuous overproduction of ammonium in vivo, and could compensate the increased requirement of ammonium detoxication. On the other hand, after administration of ammonium chloride, in the rats with damaged liver, the induction of the enzymes in these metabolic pathways above was not encountered, the activities of the enzymes were rather decreased, and plasma contents of citrulline and glutamic acid were markedly increased. These findings indicated that there were lowered metabolic activities on the ammonium detoxication in the damaged liver, and these insufficiencies was further enhanced by the overproduction of ammonium.Six isoenzymes of glutamic dehydrogenase isolated from mitochondria) fraction of rat liver were found, however, the specific isoenzymes related to ammonium doxication were not evidenced.From these results above mentioned, it was concluded that impaired activities of hepatic enzymes in urea cycle and the metabolic pathway of glutamic acid were an essential aetiologic factor accounting for the incidence of hyperammoniaemia.
財団法人日本消化器病学会の論文

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玉井義朗
京都大学医学部第二内科

Enzymological studies on ammonium detoxication in liver:I. Measurement of the activities of urea cycle enzymes and the enzymes concerning with glutamic acid metabolism in liver after ammonium chloride administration

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