Kinetic analysis of a new human ornithine carbamoyltransferase variant

A new human enzymatic variant was found in a patient with ornithine carbamoyltransferase (carbamoylphosphate:L-ornithine carbamoyltransferase, EC 2.1.3.3) deficiency. This mutant enzyme has decreased affinity, with an abnormal Km value for ornithine (3-5-times greater than control at all pH values). The maximal velocity (V) varied with pH as a normal enzyme but the sigmoid curve obtained (V vs. pH) is shifted towards alkaline pH values. The pK of the functional catalytic group is 8.3 instead of 6.65 of a control enzyme. At its optimum pH the V of the mutant enzyme is greater than the V of the normal enzyme. Other mutant enzyme proteins with abnormal affinity for ornithine have already been described. They all are different from the reported here.