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p-Hydroxyphenylacetaldehyde, the major product of L-tyrosine oxidation by the myeloperoxidase-H2O2-chloride system of phagocytes, covalently modifies epsilon-amino groups of protein lysine residues.
J Biol Chem 1997; 272(27):16990-8JB

Abstract

Activated human phagocytes employ the myeloperoxidase-H2O2-Cl- system to convert L-tyrosine to p-hydroxyphenylacetaldehyde (pHA). We have explored the possibility that pHA covalently reacts with proteins to form Schiff base adducts, which may play a role in modifying targets at sites of inflammation. Because Schiff bases are labile to acid hydrolysis, prior to analysis the adducts were rendered stable by reduction with NaCNBH3. Purified pHA reacted with Nalpha-acetyllysine, an analog of protein lysine residues. The reduced reaction product was identified as Nalpha-acetyl-Nepsilon-(2-(p-hydroxyphenyl)ethyl)lysine by 1H NMR spectroscopy and mass spectrometry. The compound Nepsilon-(2-(p-hydroxyphenyl)ethyl)lysine (pHA-lysine) was likewise identified in acid hydrolysates of bovine serum albumin (BSA) that were first exposed to myeloperoxidase, H2O2, L-tyrosine, and Cl- and then reduced with NaCNBH3. Other halides (F-, Br-, I-) and the pseudohalide SCN- could not replace Cl- as a substrate in the myeloperoxidase-H2O2-L-tyrosine system. In the absence of the enzymatic system, pHA-lysine was detected in reduced reaction mixtures of BSA, L-tyrosine, and reagent HOCl. In contrast, pHA-lysine was undetectable when BSA was incubated with L-tyrosine and HOBr, peroxynitrite, hydroxyl radical, or a variety of other peroxidases, indicating that the aldehyde-protein adduct was selectively produced by HOCl. Human neutrophils activated in the presence of tyrosine also modified BSA lysine residues. pHA-lysine formation required L-tyrosine and cell activation; it was inhibited by peroxidase inhibitors and catalase, implicating myeloperoxidase and H2O2 in the reaction pathway. pHA-lysine was detected in inflamed human tissues that were reduced, hydrolyzed, and then analyzed by mass spectrometry, indicating that the reaction of pHA with proteins may be of physiological importance. These observations raise the possibility that the identification of pHA-lysine in tissues will pinpoint targets where phagocytes inflict oxidative damage in vivo.

Authors+Show Affiliations

Department of Medicine, Washington University, St. Louis, Missouri 63110, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9202012

Citation

Hazen, S L., et al. "P-Hydroxyphenylacetaldehyde, the Major Product of L-tyrosine Oxidation By the myeloperoxidase-H2O2-chloride System of Phagocytes, Covalently Modifies Epsilon-amino Groups of Protein Lysine Residues." The Journal of Biological Chemistry, vol. 272, no. 27, 1997, pp. 16990-8.
Hazen SL, Gaut JP, Hsu FF, et al. P-Hydroxyphenylacetaldehyde, the major product of L-tyrosine oxidation by the myeloperoxidase-H2O2-chloride system of phagocytes, covalently modifies epsilon-amino groups of protein lysine residues. J Biol Chem. 1997;272(27):16990-8.
Hazen, S. L., Gaut, J. P., Hsu, F. F., Crowley, J. R., d'Avignon, A., & Heinecke, J. W. (1997). P-Hydroxyphenylacetaldehyde, the major product of L-tyrosine oxidation by the myeloperoxidase-H2O2-chloride system of phagocytes, covalently modifies epsilon-amino groups of protein lysine residues. The Journal of Biological Chemistry, 272(27), pp. 16990-8.
Hazen SL, et al. P-Hydroxyphenylacetaldehyde, the Major Product of L-tyrosine Oxidation By the myeloperoxidase-H2O2-chloride System of Phagocytes, Covalently Modifies Epsilon-amino Groups of Protein Lysine Residues. J Biol Chem. 1997 Jul 4;272(27):16990-8. PubMed PMID: 9202012.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - p-Hydroxyphenylacetaldehyde, the major product of L-tyrosine oxidation by the myeloperoxidase-H2O2-chloride system of phagocytes, covalently modifies epsilon-amino groups of protein lysine residues. AU - Hazen,S L, AU - Gaut,J P, AU - Hsu,F F, AU - Crowley,J R, AU - d'Avignon,A, AU - Heinecke,J W, PY - 1997/7/4/pubmed PY - 1997/7/4/medline PY - 1997/7/4/entrez SP - 16990 EP - 8 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 272 IS - 27 N2 - Activated human phagocytes employ the myeloperoxidase-H2O2-Cl- system to convert L-tyrosine to p-hydroxyphenylacetaldehyde (pHA). We have explored the possibility that pHA covalently reacts with proteins to form Schiff base adducts, which may play a role in modifying targets at sites of inflammation. Because Schiff bases are labile to acid hydrolysis, prior to analysis the adducts were rendered stable by reduction with NaCNBH3. Purified pHA reacted with Nalpha-acetyllysine, an analog of protein lysine residues. The reduced reaction product was identified as Nalpha-acetyl-Nepsilon-(2-(p-hydroxyphenyl)ethyl)lysine by 1H NMR spectroscopy and mass spectrometry. The compound Nepsilon-(2-(p-hydroxyphenyl)ethyl)lysine (pHA-lysine) was likewise identified in acid hydrolysates of bovine serum albumin (BSA) that were first exposed to myeloperoxidase, H2O2, L-tyrosine, and Cl- and then reduced with NaCNBH3. Other halides (F-, Br-, I-) and the pseudohalide SCN- could not replace Cl- as a substrate in the myeloperoxidase-H2O2-L-tyrosine system. In the absence of the enzymatic system, pHA-lysine was detected in reduced reaction mixtures of BSA, L-tyrosine, and reagent HOCl. In contrast, pHA-lysine was undetectable when BSA was incubated with L-tyrosine and HOBr, peroxynitrite, hydroxyl radical, or a variety of other peroxidases, indicating that the aldehyde-protein adduct was selectively produced by HOCl. Human neutrophils activated in the presence of tyrosine also modified BSA lysine residues. pHA-lysine formation required L-tyrosine and cell activation; it was inhibited by peroxidase inhibitors and catalase, implicating myeloperoxidase and H2O2 in the reaction pathway. pHA-lysine was detected in inflamed human tissues that were reduced, hydrolyzed, and then analyzed by mass spectrometry, indicating that the reaction of pHA with proteins may be of physiological importance. These observations raise the possibility that the identification of pHA-lysine in tissues will pinpoint targets where phagocytes inflict oxidative damage in vivo. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/9202012/p_Hydroxyphenylacetaldehyde_the_major_product_of_L_tyrosine_oxidation_by_the_myeloperoxidase_H2O2_chloride_system_of_phagocytes_covalently_modifies_epsilon_amino_groups_of_protein_lysine_residues_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=9202012 DB - PRIME DP - Unbound Medicine ER -