Cresyl saligenin phosphate makes multiple adducts on free histidine, but does not form an adduct on histidine 438 of human butyrylcholinesterase.
Cresyl saligenin phosphate (CBDP) is a suspected causative agent of "aerotoxic syndrome", affecting pilots, crew members and passengers. CBDP is produced in vivo from ortho-containing isomers of tricresyl phosphate (TCP), a component of jet engine lubricants and hydraulic fluids. CBDP irreversibly inhibits butyrylcholinesterase (BChE) in human plasma by forming adducts on the active site serine (Ser-198). Inhibited BChE undergoes aging to release saligenin and o-cresol. The active site histidine (His-438) was hypothesized to abstract o-hydroxybenzyl moiety from the initial adduct on Ser-198. Our goal was to test this hypothesis. Mass spectral analysis of CBDP-inhibited BChE digested with Glu-C showed an o-hydroxybenzyl adduct (+106 amu) on lysine 499, a residue far from the active site, but not on His-438. Nevertheless, the nitrogen of the imidazole ring of free L-histidine formed a variety of adducts upon reaction with CBDP, including the o-hydroxybenzyl adduct, suggesting that histidine-CBDP adducts may form on other proteins.
Department of Environmental, Agricultural & Occupational Health, University of Nebraska Medical Center, Omaha, NE 68198-5950, USA.
Mariya S
MS
Liyasova
Lawrence M
LM
Schopfer
Oksana
O
Lockridge
D000337:Aerospace Medicine; D000401:Aircraft; D002091:Butyrylcholinesterase / Q000737:chemistry* / Q000378:metabolism*; D020134:Catalytic Domain; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D005648:Fuel Oils / Q000633:toxicity; D006639:Histidine / Q000737:chemistry; D006801:Humans; D009943:Organophosphorus Compounds / Q000633:toxicity*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013577:Syndrome
D002800:Cholinesterase Inhibitors; D005648:Fuel Oils; D009943:Organophosphorus Compounds; C000516:2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide; D006639:Histidine; D002091:Butyrylcholinesterase