Urea synthesis by liver homogenates.

The synthesis of citrulline from ornithine and arginine from citrulline has heretofore been associated only with intact liver cells. In the course of studies on the mechanism of the conversion of citrulline to a&nine, a highly active system was found in liver homogenate capable of forming urea in the presence of glutamic acid, adenosine triphosphate (ATP), cytochrome c, an oxygen atmosphere, and magnesium ions. The obvious similarity of the substrates, citrulline and glutamic acid, to that required for the transimination system found by Borsook and Dubnoff (9) in kidney slices led us to a general study of this reaction in rat tissue slices and homogenates (10). The r&e of glutamic acid as the imino group donor to arginine was shown to be very specific, not replaceable by other similar compounds (except glutamine) or by ammonium chloride. In previous work (ll), it was reported that liver slices synthesized urea to a limited extent only from citrulline and glutamic acid, more readily from ammonium chloride, and to a considerable extent when both ammonium chloride and glutamic acid were provided. In the present paper, data will be presented which demonstrate in liver the presence of a potent transimination system which in all probability is the mechanism by which citrulline is converted to arginine in the urea cycle.