Metabolic cooperation between argininosuccinate synthetase and argininosuccinate lyase deficient human fibroblasts.

Human fibroblasts deficient in either argininosuccinate synthetase or argininosuccinate lyase show low levels of incorporation of [14C]citrulline into protein. However, when these two cell types are co-cultured [14C]citrulline incorporation is restored to the levels found in control cultures. This metabolic cooperation is cell-density-dependent and does not occur by diffusion of argininosuccinate into the medium. Our results indicate that argininosuccinate passes between the two cell types via intercellular junctions, and this system provides a simple and accurately quantifiable model for the study of intercellular communication.