تسجيل الدخول

تسجيل

Nitrogen Excretion and the Urea Cycle: -The Activity of the Urea Cycle Is Regulated at Two Levels

المؤلف:  David L. Nelson، Michael M. Cox

المصدر:  Lehninger Principles of Biochemistry

الجزء والصفحة:  669

2026-06-14

34

Nitrogen Excretion and the Urea Cycle:-The Activity of the Urea Cycle Is Regulated at Two Levels

The flux of nitrogen through the urea cycle in an individual animal varies with diet. When the dietary intake is primarily protein, the carbon skeletons of amino acids are used for fuel, producing much urea from the excess amino groups. During prolonged starvation, when break down of muscle protein begins to supply much of the organism’s metabolic energy, urea production also increases substantially. These changes in demand for urea cycle activity are met over the long term by regulation of the rates of syn thesis of the four urea cycle enzymes and carbamoyl phosphate synthetase I in the liver. All five enzymes are synthesized at higher rates in starving animals and in animals on very-high-protein diets than in well-fed animals eating primarily carbohydrates and fats. Animals on protein-free diets produce lower levels of urea cycle enzymes. On a shorter time scale, allosteric regulation of at least one key enzyme adjusts the flux through the urea cycle. The first enzyme in the pathway, carbamoyl phosphate synthetase I, is allosterically activated by N-acetylglutamate, which is synthesized from acetyl CoA and glutamate by N-acetylglutamate synthase (Fig. 18–13). In plants and microorganisms this enzyme catalyzes the first step in the de novo synthesis of argi nine from glutamate, but in mammals N-acetylglutamate synthase activity in the liver has a purely regulatory function (mammals lack the other en zymes needed to convert glutamate to arginine). The steady-state levels of N-acetylglutamate are determined by the concentrations of glutamate and acetyl-CoA (the substrates for N-acetylglutamate synthase) and arginine (an activator of N-acetylglutamate synthase, and thus an activator of the urea cycle).

FIGURE 18–13 Synthesis of N-acetylglutamate and its activation of carbamoyl phosphate synthetase I.