Reaction of human albumin with aspirin in vitro

Mass spectrometric identification of acetylated lysines 199, 402, 519, and 545

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44 Citations (Scopus)

Abstract

The aspirin esterase activity of human plasma is due to butyrylcholinesterase and albumin. Our goal was to identify the amino acid residues involved in the aspirin esterase activity of albumin. Fatty acid-free human albumin and human plasma were treated with aspirin for 5 min-24 h. Acetylated residues were identified by LC/MS/MS and MALDI-TOF/TOF mass spectrometry of tryptic peptides. Treatment with 0.3 mM aspirin resulted in acetylation of Lys-199, Lys-402, Lys-519, and Lys-545. Treatment with 20 mM aspirin resulted in acetylation of 26 lysines. There was no acetylation of Tyr-411, under any conditions. Acetylated lysine was stable for at least 21 days at pH 7.4, 37 °C. Albumin acetylated by aspirin had reduced esterase activity with β-naphthyl acetate as shown on gels stained for esterase activity. It was concluded that the aspirin esterase activity of albumin is a pseudo-esterase activity in which aspirin stably acetylates lysines and releases salicylate.

Original languageEnglish (US)
Pages (from-to)784-791
Number of pages8
JournalBiochemical Pharmacology
Volume79
Issue number5
DOIs
StatePublished - Mar 1 2010

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Aspirin
Lysine
Albumins
Acetylation
Esterases
Plasma (human)
Butyrylcholinesterase
Salicylates
Matrix-Assisted Laser Desorption-Ionization Mass Spectrometry
Nonesterified Fatty Acids
Human Activities
Serum Albumin
Mass spectrometry
Mass Spectrometry
Gels
In Vitro Techniques
Amino Acids
Peptides
acetylsalicylic acid hydrolase

Keywords

  • Acetylated lysine
  • Albumin
  • Aspirin
  • Mass spectrometry
  • Pseudo-aspirinase activity

ASJC Scopus subject areas

  • Biochemistry
  • Pharmacology

Cite this

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abstract = "The aspirin esterase activity of human plasma is due to butyrylcholinesterase and albumin. Our goal was to identify the amino acid residues involved in the aspirin esterase activity of albumin. Fatty acid-free human albumin and human plasma were treated with aspirin for 5 min-24 h. Acetylated residues were identified by LC/MS/MS and MALDI-TOF/TOF mass spectrometry of tryptic peptides. Treatment with 0.3 mM aspirin resulted in acetylation of Lys-199, Lys-402, Lys-519, and Lys-545. Treatment with 20 mM aspirin resulted in acetylation of 26 lysines. There was no acetylation of Tyr-411, under any conditions. Acetylated lysine was stable for at least 21 days at pH 7.4, 37 °C. Albumin acetylated by aspirin had reduced esterase activity with β-naphthyl acetate as shown on gels stained for esterase activity. It was concluded that the aspirin esterase activity of albumin is a pseudo-esterase activity in which aspirin stably acetylates lysines and releases salicylate.",
keywords = "Acetylated lysine, Albumin, Aspirin, Mass spectrometry, Pseudo-aspirinase activity",
author = "Liyasova, {Mariya S.} and Schopfer, {Lawrence M} and Oksana Lockridge",
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T1 - Reaction of human albumin with aspirin in vitro

T2 - Mass spectrometric identification of acetylated lysines 199, 402, 519, and 545

AU - Liyasova, Mariya S.

AU - Schopfer, Lawrence M

AU - Lockridge, Oksana

PY - 2010/3/1

Y1 - 2010/3/1

N2 - The aspirin esterase activity of human plasma is due to butyrylcholinesterase and albumin. Our goal was to identify the amino acid residues involved in the aspirin esterase activity of albumin. Fatty acid-free human albumin and human plasma were treated with aspirin for 5 min-24 h. Acetylated residues were identified by LC/MS/MS and MALDI-TOF/TOF mass spectrometry of tryptic peptides. Treatment with 0.3 mM aspirin resulted in acetylation of Lys-199, Lys-402, Lys-519, and Lys-545. Treatment with 20 mM aspirin resulted in acetylation of 26 lysines. There was no acetylation of Tyr-411, under any conditions. Acetylated lysine was stable for at least 21 days at pH 7.4, 37 °C. Albumin acetylated by aspirin had reduced esterase activity with β-naphthyl acetate as shown on gels stained for esterase activity. It was concluded that the aspirin esterase activity of albumin is a pseudo-esterase activity in which aspirin stably acetylates lysines and releases salicylate.

AB - The aspirin esterase activity of human plasma is due to butyrylcholinesterase and albumin. Our goal was to identify the amino acid residues involved in the aspirin esterase activity of albumin. Fatty acid-free human albumin and human plasma were treated with aspirin for 5 min-24 h. Acetylated residues were identified by LC/MS/MS and MALDI-TOF/TOF mass spectrometry of tryptic peptides. Treatment with 0.3 mM aspirin resulted in acetylation of Lys-199, Lys-402, Lys-519, and Lys-545. Treatment with 20 mM aspirin resulted in acetylation of 26 lysines. There was no acetylation of Tyr-411, under any conditions. Acetylated lysine was stable for at least 21 days at pH 7.4, 37 °C. Albumin acetylated by aspirin had reduced esterase activity with β-naphthyl acetate as shown on gels stained for esterase activity. It was concluded that the aspirin esterase activity of albumin is a pseudo-esterase activity in which aspirin stably acetylates lysines and releases salicylate.

KW - Acetylated lysine

KW - Albumin

KW - Aspirin

KW - Mass spectrometry

KW - Pseudo-aspirinase activity

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