1. Plasma tyrosine and phenylalanine were measured in patients with chronic renal failure and in normal subjects. Plasma tyrosine to phenylalanine ratio was greatly decreased in patients with creatinine clearance less than 16 ml/min, suggesting an impairment of phenylalanine hydroxylation. This ratio correlated with the percentage of essential to total amino nitrogen in the plasma.

2. Phenylalanine hydroxylase from rat liver was inhibited or inactivated (15%) by uraemic plasma but this could not be attributed to the individual effects of urea, creatinine, uric acid, oxalic acid, phenylpyruvic acid, glycine or phosphate. It is unlikely that the degree of inhibition was sufficient to account for the impairment of phenylalanine hydroxylation in chronic renal insufficiency.

3. Phenylalanine hydroxylase was present in rat kidney but at a very low activity relative to that present in liver; consequently, the loss of functional kidney tissue associated with chronic renal insufficiency is unlikely to impair phenylalanine hydroxylation.

4. Plasma tyrosine and liver phenylalanine hydroxylase activity were significantly decreased in partially nephrectomized rats when protein intake was inadequate.

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