Sparse-Fur Mutation : A Model for Some Human Ornithine Transcarbamylase Deficiencies
Recently a new human enzymatic variant1 was found in a patient with ornithine transcarbamylase (OTC ; E.C.188.8.131.52.) deficiency one of the more common genetic defects occurring in the urea cycle. This mutant enzyme had a decreased affinity with an abnormal Km value for ornithine. The maximal velocity (Vmax) varied with pH as in a normal enzyme but the sigmoid curve obtained was shifted towards alkaline pHs. Furthermore at its optimum pH (pH 9) the Vmax of the mutant enzyme was greater than the Vmax of the normal enzyme at its optimum pH (pH 7.8). Two hypotheses were proposed : either the mutant enzyme was more stable than a normal one at alkaline pH or a much higher level of OTC protein due to a regulating mechanism was characteristic of this mutant. Unfortunately we had no hepatic material left after the enzymatic analysis to investigate this problem.
KeywordsMutant Enzyme Radial Immunodiffusion Ornithine Transcarbamylase Normal Enzyme Carbamyl Phosphate
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