The interaction of cycloserine with pyruvate and other biologically relevant alpha-ketoacids

The ability of cycloserine solutions to deplete alpha-oxoacids has been found to be correlated with the spontaneous transformation of cycloserine into a derivative dimer (2,5-bis-(aminoxymethyl)-3,6-diketopiperazine). Synthetic dimer was found to react rapidly with pyruvate to form the expected oxime. Two lines of evidence indicate that it is the cycloserine dimer and not cycloserine itself that reacts with alpha-ketoacid. First, the 1H NMR spectrum of the purified oxime is superimposable with that arising when the dimer and pyruvate are mixed and the spectrum taken immediately thereafter. Second, the mass spectrum of the reaction product of cycloserine dimer and methylpyruvate is totally consistent with the formation of a stable oxime derivative. Furthermore, when cycloserine is incubated with pyruvate the oxime derived from the dimer is found. These observations clearly indicate that cycloserine in solution can have chemical activities in addition to its ability to interfere with pyridoxal dependent reactions. On these grounds it is concluded that any biological action of cycloserine should be interpreted cautiously.