Cresyl saligenin phosphate makes multiple adducts on free histidine, but does not form an adduct on histidine 438 of human butyrylcholinesterase

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)103-107
Number of pages5
JournalChemico-Biological Interactions
Volume203
Issue number1
DOIs
StatePublished - Mar 25 2013

Keywords

  • Aging
  • Butyrylcholinesterase
  • CBDP
  • Histidine
  • TCP
  • o-Hydroxybenzyl

ASJC Scopus subject areas

  • Toxicology

Fingerprint Dive into the research topics of 'Cresyl saligenin phosphate makes multiple adducts on free histidine, but does not form an adduct on histidine 438 of human butyrylcholinesterase'. Together they form a unique fingerprint.

  • Cite this