Inhibition of amino acid transport into lymphoid cells by the glutamine analog L-2-amino-4-oxo-5-chloropentanoate.

Abstract

Transport of L-glutamine and of the chloroketone glutamine analog L-2-amino-4-oxo-5-chloropentanoate into lymphoid cells is mediated by the same system. Arginine and a number of other amino acids (e.g., glutamate, aspartate and lysine) are transported to a much lesser extent by this system. After uptake of the chloroketone into the cells, the transport of glutamine, arginine and other amino acids is markedly inhibited, due evidently to reaction of the chloroketone with intracellular components that are involved in amino acid transport. The chloroketone acts more effectively on growing than on resting cells. Treatment of [human RPMI 1788] lymphoid cells with the chloroketone or with 1-chloro-2,4-dinitrobenzene leads to rapid and complete depletion of intracellular glutathione without affecting cell viability. These reagents appear to be useful experimental tools for studies of glutathione function and metabolism.