Myeloperoxidase-catalyzed binding of 3-amino-1-methyl-5H-pyrido[4,3-b]indole, a tryptophan pyrolysis product, to protein.
Incorporation of 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), the principal mutagen in a tryptophan pyrolysate, into bovine serum albumin was catalyzed by myeloperoxidase. Hydrogen peroxide was essential for the incorporation reaction and albumin was required for optimal incorporation of Trp-P-2 into protein. Other various proteins, such as histone, lysozyme, cytochrome c, and gamma-globulin could also incorporate Trp-P-2, but poly(L-Arg), poly(L-Lys), and poly(L-Glu) could not. The incorporation of Trp-P-2 into albumin was inhibited by L-tyrosine and L-tryptophan, but not by other amino acids. Trp-P-2 incorporated into albumin was not released from the protein by treatment with 0.3 N HCl, or 0.3 N NaOH for 2 h at 35 degrees C, or with 1% sodium dodecylsulfate for 2.5 min at 100 degrees C. On electrophoresis on polyacrylamide containing sodium dodecylsulfate or urea and on chromatography on Sepharose CL-6B in 6 M guanidine/HCl, Trp-P-2 incorporated into albumin or lysozyme migrated with these proteins. These findings indicate that Trp-P-2 is covalently bound to these acceptor proteins.
D000418:Albumins / Q000096:biosynthesis; D000596:Amino Acids / Q000378:metabolism; D002243:Carbolines / Q000378:metabolism*; D006146:Guanidines / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism*; D009113:Muramidase / Q000378:metabolism; D009153:Mutagens / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D011485:Protein Binding
D000418:Albumins; D000596:Amino Acids; D002243:Carbolines; D006146:Guanidines; D007211:Indoles; D009153:Mutagens; C019133:3-amino-1-methyl-5H-pyrido(4,3-b)indole; D006861:Hydrogen Peroxide; D010544:Peroxidases; D009195:Peroxidase; D009113:Muramidase