Benzodiazepines: specific competitors for the binding of L-tryptophan to human serum albumin.
By means of the gel filtration technique, the effect of nine benzodiazepine derivatives on the binding of L-tryptophan to human serum albumin was investigated. Using equimolar tryptophan and benzodiazepine concentrations, all benzodiazepines with binding constants higher than 10(4) (M(-1), displace L-tryptophan from its binding site to a high degree. The mechanism of the displacement was characterized as a competition for a common binding site. Some of the benzodiazepines displace L-tryptophan to a greater extent than salicylic acid. The benzostereospecific binding to human serum albumin. This study shows that there is only one binding site on the human serum albumin molecule, which binds tryptophan and the benzodiazepines in a highly stereospecific manner. Therefore it is concluded that the benzodiazepines and L-tryptophan must have similarities in their molecular structure, so that both can bind to the common binding site in such specific manner. These considerations are discussed in regard to the known influence of benzodiazepine derivatives on the L-tryptophan metabolism in brain. A direct involvement of the reported displacement in the pharmacological actions of the drugs seems not to be relevant because of their small therapeutical plasma levels.
D000818:Animals; D001569:Benzodiazepines / Q000097:blood* / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D002850:Chromatography, Gel; D006801:Humans; D011485:Protein Binding; D012459:Salicylates / Q000097:blood; D012709:Serum Albumin / Q000378:metabolism*; D012710:Serum Albumin, Bovine / Q000378:metabolism; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000097:blood*
D012459:Salicylates; D012709:Serum Albumin; D001569:Benzodiazepines; D012710:Serum Albumin, Bovine; D014364:Tryptophan