Modification of phosphatidylserine by hypochlorous acid.
The binding of the heme enzyme myeloperoxidase to phosphatidylserine epitopes on the surface of non-vital polymorphonuclear leukocytes and other cells at inflammatory sites favours modifications of this phospholipid by myeloperoxidase products. As detected by MALDI-TOF mass spectrometry hypochlorous acid and the myeloperoxidase-hydrogen peroxide-chloride system convert 1,2-dipalmitoyl-sn-glycero-3-phosphoserine into 1,2-dipalmitoyl-sn-glycero-3-phosphoacetaldehyde and 1,2-dipalmitoyl-sn-glycero-3-phosphonitrile. A transient chlorimine derivative was detected using 4-chloro-alpha-cyanocinnamic acid as matrix in mass spectrometry only at short incubation times and supplying HOCl in two-fold excess. The decay of transient chlorinated products was followed by changes in absorbance spectra using O-phospho-l-serine to model the behavior of the serine head group in phosphatidylserine. N-Chlorimine and N-monochloramine derivatives decayed with half-life times of 1.5 and 57 min, respectively, at 22 degrees C and pH 7.4. N-Dichloramines decayed within few seconds under these conditions.
Flemmig
Joerg
J
Institute for Medical Physics and Biophysics, Medical Department, University of Leipzig, D-04107 Leipzig, Germany.
Spalteholz
Holger
H
Schubert
Katja
K
Meier
Sandra
S
Arnhold
Juergen
J
D002700:Chloramines / Q000378:metabolism; D002934:Cinnamates; D006861:Hydrogen Peroxide / Q000378:metabolism; D006997:Hypochlorous Acid / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism*; D010718:Phosphatidylserines / Q000378:metabolism*; D012694:Serine / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013696:Temperature
C532442:4-chloro-alpha-cyanocinnamic acid; D002700:Chloramines; D002934:Cinnamates; D010718:Phosphatidylserines; D012694:Serine; D006997:Hypochlorous Acid; D006861:Hydrogen Peroxide; D009195:Peroxidase; C030816:chloramine