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 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(-4) M) diminishes the inhibitory effect of binding due to excess unlabeled L-tryptophan (10(-4) M). 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 is 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.
Sidransky
H
H
Department of Pathology, George Washington University Medical Center, Washington, DC 20037.
Verney
E
E
Cosgrove
J W
JW
Latham
P S
PS
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004340:Drug Contamination; D005260:Female; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000378:metabolism* / Q000648:ultrastructure; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D009685:Nuclear Envelope / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium; D014364:Tryptophan / Q000378:metabolism*
D014316:Tritium; C078798:3-(phenylamino)alanine; D014364:Tryptophan; D000409:Alanine