Argininosuccinate synthetase activity and citrulline metabolism in cells cultured from a citrullinemic subject.

Citrullinemia-is one of several human diseases caused by a defect in the KrebsHenseleit urea cycle. In this disorder a deficiency of liver argininosuccinate synthetase has been reported.' 1\Iorrow and his colleagues have recently described an infant with this condition2 and a fibroblast-like cell line has been derived from a skin biopsy of this child. In studying minimal media requirements for heteroploid human cell cultures, Eagle observed that citrulline, but not ornithine, could substitute for arginine as an essential nutrient.3 This evidence for the existence of the citrulline to arginine portion of the Krebs-Henseleit cycle had also been noted in cultured chick embryo heart fibroblasts.4 We have found that extracts of diploid fibroblast-like cells cultured from human skin normally can convert citrulline to arginine, but not ornithine to citrulline (ornithine transcarbamylase) or arginine to urea (arginase).5 We have compared the growth requirements and the properties of argininosucciinate synthetase in normal human cells and cells cultured from the skin of an infant vith citrullinernia. Our findings provide evidence for the genetic nature of this human disorder.