Alteration in arginine activation of N-acetylglutamate synthetase in vitro by disulfide or thiol compounds

Abstract

N-acetyl- l-glutamate synthetase (EC 2.3.1.1) is a regulatory enzyme involved in the control of carbamoyl-phosphate synthesis in the mammalian liver. The enzyme is activated specifically by arginine, and the sensitivity of acetylglutamate synthetase to arginine undergoes marked changes after food ingestion. Since the extent of arginine activation of the synthetase — high for the enzyme from fed mice and low for the enzyme from fasted mice — remained much the same during partial purification, these changes appear to be due to a modification of the enzyme molecule itself. When the enzyme preparation with a low sensitivity to arginine activation, partially purified from the liver of starved mice, was incubated with thiol compounds, the sensitivity increased. When the enzyme preparation with a high sensitivity, obtained from the liver of fed mice, was incubated with disulfide compounds, the sensitivity decreased. Diminution and enhancement of arginine sensitivity of a single enzyme preparation were also achieved by the disulfide and thiol treatments, thereby revealing the reversibility of the process. These results suggest that thiol/disulfide interchange may be involved in the regulation of arginine sensitivity of acetylglutamate synthetase in vivo.