Control of arginine metabolism in Neurospora crassa. Role of feedback inhibition.

Flux through the arginine biosynthetic pathway of Neurospora crassa was measured under a variety of physiological conditions. Flux persisted, although at a reduced rate, in mutant strains resistant to feedback inhibition even after prolonged growth in the presence of exogenous arginine. Flux reverted to the uninhibited rate more quickly in feedback-resistant strains than in wild type strains upon removal of exogenous arginine. These results rule out enzyme repression as a major factor in controlling arginine biosynthesis. Feedback inhibition was shown to be independent of the size of the mycelial arginine pool or of the cytosolic arginine concentration, suggesting a role for the mitochondrial membrane in controlling the concentration of arginine at the site of inhibition--the mitochondrial matrix. The implications of these results are discussed.