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

N-acetyl-L-glutamate synthetase (EC 2.3.1.1) is a regulatory enzyme involve d in the control of carbamoyl-phosphate synthesis in the mammalian liver. T he enzyme is activated specifically by arginine, and the sensitivity of ace tylglutamate synthetase to arginine undergoes marked changes after food ing estion. Since the extent of arginine activation of the synthetase - high fo r the enzyme from fed mice and low for the enzyme from fasted mice - remain ed much the same during partial purification, these changes appear to be du e to a modification of the enzyme molecule itself. When the enzyme preparat ion with a low sensitivity to arginine activation, partially purified from the liver of starved mice, was incubated with thiol compounds, the sensitiv ity increased. When the enzyme preparation with a high sensitivity, obtaine d from the liver of fed mice, was incubated with disulfide compounds, the s ensitivity 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 resul ts suggest that thiol/disulfide interchange may be involved in the regulati on of arginine sensitivity of acetylglutamate synthetase in vivo. (C) 2000 Elsevier Science B.V. All rights reserved.