Enzymes of Arginine Metabolism in Mammalian Cell Culture. I. Repression of Argininosuccinate Synthetase and Argininosuccinase.

I f a universality of biological phenomena exists, it would be expected that the control of enzyme levels in mammalian tissues conform, at least in part, to the classic induction-repression phenomenon as observed in numerous bacterial systems (2). However, to date, distinct repression phenomena in mammalian systems have been observed only in the case of glycine transamidinase in chicken (3, 4) and rat (5), n-glutamyl transferase in a HeLa cell strain (6), and aspartate transcarbamylase in Sarcoma 180 cells (7). This paper describes another example of what appears to be a repression phenomenon, that related to the effects of arginine on two enzymes involved in arginine biosynthesis in a number of serially propagated mammalian cell lines. Mammalian cells have limited capacities for amino acid biosynthesis (8), and consequently opportunities for studying control of enzymes of amino acid biosynthetic pathways are limited. However, one such capability involves the conversion of citrulline to arginine, since citrulline, but not ornithine, has been shown to satisfy the arginine growth requirement of a number of cell lines (8-10). The pathway of arginine metabolism concerned in these studies is shown below: