Title

Effect of 3-phenylamino-l-alanine on tryptophan binding to rat hepatic nuclear envelopes

Document Type

Journal Article

Publication Date

1-26-1994

Journal

Toxicology

Volume

86

Issue

1-2

DOI

10.1016/0300-483X(94)90058-2

Keywords

3-Phenylamino-l-alanine; In vitro protein synthesis; In vitro tryptophan binding; Liver nuclear envelope

Abstract

We have determined that the addition of 3-phenylamino-l-alanine (PAA), a recently reported contaminant in l-tryptophan implicated in the eosinophilia-myalgia syndrome, affects tryptophan binding by utilizing an in vitro measurement of 3H-tryptophan binding to hepatic nuclei or nuclear envelopes. PAA (10-10 to 10-4M) diminishes the inhibitory effect of binding due to excess unlabeled l-tryptophan (10-4M). PAA alone has no inhibitory effect on binding. The effect of PAA on in vitro tryptophan binding is in contrast to that of another contaminant, 1,1′-ethylidenebis(tryptophan), which together with excess unlabeled l-tryptophan does not appreciably affect the binding. In vitro addition of PAA and l-tryptophan to nuclei of rat brain or of cultured murine macrophages does not affect [3H]tryptophan binding in comparison to l-tryptophan alone as if the case with hepatic nuclear envelopes. Adding PAA to an in vitro protein synthesis system and measuring [3H]tryptophan or [3H]alanine incorporation into acid-precipitable proteins reveals that it competes similarly, but somewhat less, than does equimolar concentrations of unlabeled l-tryptophan or l-alanine, respectively. This suggests that PAA or a breakdown compound becomes incorporated into proteins. Speculation as to how PAA may affect tissues in experimental animals is presented. © 1994.

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