Enzymes of Ammonia Detoxication after Portacaval Shunt in the Rat

Abstract

At high systemic blood concentrations ammonia may be partially deviated into the pathway of pyrimidine synthesis, as has been observed in different genetic defects of the urea cycle. The portacaval shunt (PCS) rat presents an animal model to study ammonia detoxication without an underlying enzyme defect in the urea cycle. Since ammonia may induce a deviation into the pyrimidine pathway by influencing enzymatic reactions involved in this pathway, the activity of carbamylphosphate synthetase and aspartate transcarbamyiase in liver as well as the excretion of orotic acid in the urine were measured in rats 10, 20 and 30 days after PCS. The results suggest that in this experimental model ammonia may be channeled into the pyrimidine pathway leading to a stimulation of the first enzymatic step and to an increased excretion of orotic acid.

Region-selective glutamine synthetase expression in the rat central nervous system following portocaval anastomosis

“…Our results, which showed a layer-specific distribution of astrocytic GS immunolabelling, differ from those obtained in studies of tissue homogenates from PCAexposed brains, which report reduction [14] or no modification in GS activity [7,13]. These discrepancies may be explained by the fact that immunoreactivity and enzyme activity measure different entities.…”

Cerebral Ammonia Metabolism in Hyperammonemic Rats

“…Our findings of no change in the glutamine synthetase activity in the brains of 14-week portacaval-shunted rats (Table 1) are in keeping with the above-mentioned reports. On balance, the present work and the work of Colombo et al (1977) andO'Neill andO'Donovan (1979) would suggest that the rat is unable to alter the levels of many enzymes of glutamatelammonia metabolism significantly in the whole brain in the face of prolonged hyperammonemia. However, these results do not rule out transient or local changes in the levels of some or all of these enzymes.…”

“…There have been several reports on the levels of enzymes of gldtamateiammonia metabolism in the brains of hyperammonemic animals. Colombo et al (1977) measured glutamate dehydrogenase, glutamine synthetase, and glutaminase in the brains of portacaval-shunted rats and found a decrease in activity of glutamine synthetase and an increase in the activity of glutamate dehydrogenase and glutaminase by 30 days after the operation compared with the activities in brains of dietary controls (dietary controls were those animals with restricted nitrogen intake to match that of portacaval-shunted rats). However, when the data of Colombo et al for the portacaval-shunted rats were compared to shamoperated controls on a normal diet, there were no significant differences in the activities of the three brain enzymes.…”