Inhibition of metabolism of beta-alanine and D-beta-aminoisobutyric acid by D-cycloserine.

Significant increases in the concentrations of β-aminoisobutyric acid and β-alanine in the urine of patients under D-cycloserine treatment for tuberculosis were found during a study of biochemical changes caused by surgical operation. β-Alanine increased in all cases on the administration of cycloserine at a clinical dose. β-Aminoisobutyric acid excretion was increased by cycloserine treatment only in the genetic low excretors of this amino acid, but not in the high excretors who lack the degradative enzyme, D-β-aminoisobutyrate:pyruvate aminotransferase. Injection of cycloserine increased the concentrations of the amino acids in the liver of rats, and inhibited strongly D-β-aminoisobutyrate: pyruvate and β-alanine:α-ketoglutarate aminotransferases. The increase in the amino acids and the enzyme inhibition occurred after D-cycloserine disappeared from the liver. The inhibition was not caused by D-cycloserine itself, but by its metabolite, D-aminoxyalanine, which was isolated and identified from urine of rats after injection of D-cycloserine. The toxicity of D-aminoxyalanine was also determined using mice, and the relation with clinical toxic effects of D-cycloserine is discussed.