The simulation of the urea cycle: correlation of effects due to inborn errors in the catalytic properties of the enzymes with clinical-biochemical observations.
Steady-state rate equations are written on the basis of information obtained from the literature describing the kinetics of the four enzyme-catalysed reactions comprising the urea cycle. These equations are formulated into a set which also accounts for fluxes of input and output compounds external to the cycle. Numerical integration of this set of equations is performed employing parameters selected to approximate those pertaining to the operation of the urea cycle in normal liver. The result is a pattern of intermediate metabolite concentrations, which forms a basis for the comparison of patterns reflecting the effects of inborn errors of metabolism. The latter are calculated by varying specified kinetic parameters in the numerical integration. Each of the observed clinical syndromes. Hyperammonemia Types I and II, Hyperarginemia, Citrullinemia and Argininosuccinicaciduria, is discussed.
D000592:Amino Acid Metabolism, Inborn Errors / Q000201:enzymology*; D001119:Arginase / Q000378:metabolism; D001123:Argininosuccinate Lyase / Q000378:metabolism; D001124:Argininosuccinate Synthase / Q000378:metabolism; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008954:Models, Biological; D009954:Ornithine Carbamoyltransferase / Q000378:metabolism; D014508:Urea / Q000378:metabolism*
D014508:Urea; D009954:Ornithine Carbamoyltransferase; D001119:Arginase; D001123:Argininosuccinate Lyase; D002222:Carbamoyl-Phosphate Synthase (Ammonia); D001124:Argininosuccinate Synthase