Metabolic activation of the mutagen azide in biological systems.
Inorganic azide (N3-) mutagenicity is mediated through a metabolically synthesized organic azide, L-azidoalanine (N3-CH2-CH(-NH2)-COOH). L-Azidoalanine appears to be formed by the action of O-acetylserine (thiol)-Lyase (EC 4.2.99.8) using O-acetylserine and azide as substrates. In both plants and bacteria tested, azide substitutes for the natural substrate sulfide (S2-) in this reaction. Azide (L-azidoalanine) mutagenesis is highly attenuated by a deficiency in the excision of UV-like DNA damage (uvr-). Thus a premutation lesion recognizable by the bacterial excision-repair enzymes must be formed. Mutagenesis appears to proceed from this by 'direct mispairing' pathway. Azide (L-azidoalanine) mutagenicity is highly specific and involves a stereoselective process, but the molecular nature of the specificity has not been determined.
D000409:Alanine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology; D001386:Azides / Q000096:biosynthesis* / Q000378:metabolism* / Q000494:pharmacology; D001711:Biotransformation; D004249:DNA Damage; D004260:DNA Repair; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism; D010944:Plants / Q000187:drug effects / Q000378:metabolism*; D012486:Salmonella typhimurium / Q000187:drug effects; D012694:Serine / Q000031:analogs & derivatives / Q000378:metabolism; D019810:Sodium Azide; D013329:Structure-Activity Relationship
D001386:Azides; D009153:Mutagens; D012694:Serine; C039309:azidoalanine; D019810:Sodium Azide; C043943:O-acetylserine; D000409:Alanine