EFFECT OF 3-PHENYLAMINO-L-ALANINE ON TRYPTOPHAN BINDING TO RAT HEPATIC NUCLEAR ENVELOPES

We have determined that the addition of 3-phenylamino-L-alanine (PAA), a recently reported contaminant in L-tryptophan implicated in the eos inophilia-myalgia syndrome, affects tryptophan binding by utilizing an in vitro measurement of H-3-tryptophan binding to hepatic nuclei or n uclear envelopes. PAA (10(-10) to 10(-4)M) diminishes the inhibitory e ffect of binding due to excess unlabeled L-tryptophan (10(-4)M). PAA a lone has no inhibitory effect on binding. The effect of PAA on in vitr o tryptophan binding is in contrast to that of another contaminant, 1, 1'-ethylidenebis(tryptophan), which together with excess unlabeled L-t ryptophan does not appreciably affect the binding. In vitro addition o f PAA and L-tryptophan to nuclei of rat brain or of cultured murine ma crophages does not affect [H-3]tryptophan binding in comparison to L-t ryptophan alone as is the case with hepatic nuclear envelopes. Adding PAA to an in vitro protein synthesis system and measuring [H-3]tryptop han or [H-3]alanine incorporation into acid-precipitable proteins reve als that it competes similarly, but somewhat less, than does equimolar concentrations of unlabeled L-tryptpohan or L-alanine, respectively. This suggests that PAA or a breakdown compound becomes incorporated in to proteins. Speculation as to how PAA may affect tissues in experimen tal animals is presented.