The effect of endogenous l-phenyllactate on oxalate, glycolate, and glyoxylate excretion by phenylketonuric subjects

Abstract

Approximately 70% of all urinary tract stones contain oxalate. Endogenous oxalate synthesis is an important source of urinary oxalate which, in theory, should be reduced by inhibiting a key enzyme in oxalate formation. Glycolic acid oxidase is such an enzyme which can be inhibited in rats by feeding them dl-phenyllactate. Since patients with phenylketonuria (PKU) produce abnormally large amounts of l-phenyllactate, it would be expected, under this hypothesis, that endogenous oxalate synthesis would be inhibited in these patients; however, their urine was found to contain elevated levels of both oxalate and the oxalate precursors, glycolate and glyoxylate. The elevated level of oxalate was probably formed from the aromatic α-ketoacids, which are known to be elevated in PKU patients and are also known to be a source of oxalate. The elevated oxalate precursors are a result of the inhibition of glycolic acid oxidase. The theory that inhibition of glycolic acid oxidase would reduce oxalate biosynthesis is supported by two findings: (1) a significant ( p < 0.05) negative correlation of l-phenyllactate and oxalate and (2) a significant ( p < 0.05) positive correlation of l-phenyllactate and glycolate. Consequently, it was concluded that l-phenyllactate inhibits oxalate synthesis in PKU subjects despite the increased formation of oxalate from aromatic α-ketoacids. Phenyllactate should, therefore, be useful in reducing the oxalate level in patients with idiopathic recurrent kidney stones, ethylene glycol intoxication, and primary hyperoxaluria, if the required therapeutic dosage does not prove to be too large.