ARGININOSUCCINATE SYNTHETASE ACTIVITY AND CITRULLINE METABOLISM IN CELLS CULTURED FROM A CITRULLINEMIC SUBJECT

Abstract

A f ibroblast cell line from the skin of an infant with citrul-linemia was used to study the biochemical defect of this inborn error of metabolism. The growth of cell cultures was slowed when arginine was removed from the medium of both control and citrullinemia cell lines. This growth inhibition was prevented in control cells but not in citrullinemia cells by the addition of citrulline to the culture medium. Control cells incorporated C14 from citrulline to TCA-[tricarboxylic acid] precipitable cell fractions, while citrullinemia cells showed essentially no incorporation. Enzyme preparations from citrullinemia and control cells demonstrated similar capacities for converting citrulline to urea (argininosuccinate synthetase activity) when citrulline was present in high concentrations. There was no change in argininosuccinate synthetase activity when cells were grown in arginine-free medium or when citrulline was substituted for arginine in the medium. The citrullinemia cells had no argininosuccinate synthetase activity at citrulline concentrations in the range of the Km for control cells. The citrulline Km for the citrullinemia cells was at least 25 times greater than that for the normal cells.