Myeloperoxidase-catalyzed oxidation of tyrosine

Research output: Contribution to journalArticle

42 Citations (Scopus)

Abstract

The oxidation of tyr by myleoperoxidase (MPO) is postulated to play a role in atherosclerotic plaque formation. MPO has been localized in plaques and a product of MPO-catalyzed oxidation of tyr, dityrosine, also found in plaques, is proposed to be a protein crosslinking agent. We have performed kinetic studies on the oxidation of tyr by MPO and investigated the role of substrate size on its oxidation. The kinetics of MPO-catalyzed oxidation of tyr where the tyr is free tyr, the dipeptides, tripeptides, and polypeptides were studied by stopped-flow methods. The rate of reaction with enzyme intermediates compound I and compound II are decreased with increasing substrate size. The amount of dityrosine formed was also decreased with increasing substrate size. The ability of sulfhydryl compounds to inhibit MPO-dependent dityrosine formation was investigated with reduced glutathione, cys, and met. Glutathione and cys both served as substrates for MPO compound I but not compound II, whereas met was not a substrate for either compound I or II. Met, an amino acid postulated to act as a 'last chance' antioxidant for proteins, was not able to inhibit dityrosine formation from MPO-catalyzed oxidation of tyr. Glutathione and cys caused partial inhibition; however, it is possible that this inhibition was due to their ability to react directly with MPO rather than trapping the tyr radicals.

Original languageEnglish (US)
Pages (from-to)61-66
Number of pages6
JournalArchives of Biochemistry and Biophysics
Volume367
Issue number1
DOIs
StatePublished - Jul 1 1999

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Peroxidase
Tyrosine
Glutathione
Oxidation
Substrates
Dipeptides
Atherosclerotic Plaques
Sulfhydryl Compounds
Proteins
Kinetics
Antioxidants
Amino Acids
Crosslinking
Peptides
dityrosine
Enzymes

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

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title = "Myeloperoxidase-catalyzed oxidation of tyrosine",
abstract = "The oxidation of tyr by myleoperoxidase (MPO) is postulated to play a role in atherosclerotic plaque formation. MPO has been localized in plaques and a product of MPO-catalyzed oxidation of tyr, dityrosine, also found in plaques, is proposed to be a protein crosslinking agent. We have performed kinetic studies on the oxidation of tyr by MPO and investigated the role of substrate size on its oxidation. The kinetics of MPO-catalyzed oxidation of tyr where the tyr is free tyr, the dipeptides, tripeptides, and polypeptides were studied by stopped-flow methods. The rate of reaction with enzyme intermediates compound I and compound II are decreased with increasing substrate size. The amount of dityrosine formed was also decreased with increasing substrate size. The ability of sulfhydryl compounds to inhibit MPO-dependent dityrosine formation was investigated with reduced glutathione, cys, and met. Glutathione and cys both served as substrates for MPO compound I but not compound II, whereas met was not a substrate for either compound I or II. Met, an amino acid postulated to act as a 'last chance' antioxidant for proteins, was not able to inhibit dityrosine formation from MPO-catalyzed oxidation of tyr. Glutathione and cys caused partial inhibition; however, it is possible that this inhibition was due to their ability to react directly with MPO rather than trapping the tyr radicals.",
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Myeloperoxidase-catalyzed oxidation of tyrosine. / Tien, Ming.

In: Archives of Biochemistry and Biophysics, Vol. 367, No. 1, 01.07.1999, p. 61-66.

Research output: Contribution to journalArticle

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AB - The oxidation of tyr by myleoperoxidase (MPO) is postulated to play a role in atherosclerotic plaque formation. MPO has been localized in plaques and a product of MPO-catalyzed oxidation of tyr, dityrosine, also found in plaques, is proposed to be a protein crosslinking agent. We have performed kinetic studies on the oxidation of tyr by MPO and investigated the role of substrate size on its oxidation. The kinetics of MPO-catalyzed oxidation of tyr where the tyr is free tyr, the dipeptides, tripeptides, and polypeptides were studied by stopped-flow methods. The rate of reaction with enzyme intermediates compound I and compound II are decreased with increasing substrate size. The amount of dityrosine formed was also decreased with increasing substrate size. The ability of sulfhydryl compounds to inhibit MPO-dependent dityrosine formation was investigated with reduced glutathione, cys, and met. Glutathione and cys both served as substrates for MPO compound I but not compound II, whereas met was not a substrate for either compound I or II. Met, an amino acid postulated to act as a 'last chance' antioxidant for proteins, was not able to inhibit dityrosine formation from MPO-catalyzed oxidation of tyr. Glutathione and cys caused partial inhibition; however, it is possible that this inhibition was due to their ability to react directly with MPO rather than trapping the tyr radicals.

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