Kinetic analysis of the reactions of hypobromous acid with protein components: implications for cellular damage and use of 3-bromotyrosine as a marker of oxidative stress
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Kinetic analysis of the reactions of hypobromous acid with protein components : implications for cellular damage and use of 3-bromotyrosine as a marker of oxidative stress. / Pattison, David I; Davies, Michael Jonathan.
In: Biochemistry, Vol. 43, No. 16, 27.04.2004, p. 4799-809.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Kinetic analysis of the reactions of hypobromous acid with protein components
T2 - implications for cellular damage and use of 3-bromotyrosine as a marker of oxidative stress
AU - Pattison, David I
AU - Davies, Michael Jonathan
PY - 2004/4/27
Y1 - 2004/4/27
N2 - Hypohalous acids (HOX, X = Cl, Br) are produced by activated neutrophils, monocytes, eosinophils, and possibly macrophages. These oxidants react readily with biological molecules, with amino acids and proteins being major targets. Elevated levels of halogenated Tyr residues have been detected in proteins isolated from patients with atherosclerosis, asthma, and cystic fibrosis, implicating the production of HOX in these diseases. The quantitative significance of these findings requires knowledge of the kinetics of reaction of HOX with protein targets, and such data have not been previously available for HOBr. In this study, rate constants for reaction of HOBr with protein components have been determined. The second-order rate constants (22 degrees C, pH 7.4) for reaction with protein sites vary by 8 orders of magnitude and decrease in the order Cys > Trp approximately Met approximately His approximately alpha-amino > disulfide > Lys approximately Tyr > Arg > backbone amides > Gln/Asn. For most residues HOBr reacts 30-100 fold faster than HOCl, though Cys and Met residues are approximately 10-fold less reactive, and ring halogenation of Tyr is approximately 5000-fold faster. Thus, Tyr residues are more, and Cys and Met much less, important targets for HOBr than HOCl. Kinetic models have been developed to predict the targets of HOX attack on proteins and free amino acids. Overall, these results shed light on the mechanisms of cell damage induced by HOX and indicate, for example, that the 3-chloro-Tyr:3-bromo-Tyr ratio does not reflect the relative roles of HOCl and HOBr in disease processes.
AB - Hypohalous acids (HOX, X = Cl, Br) are produced by activated neutrophils, monocytes, eosinophils, and possibly macrophages. These oxidants react readily with biological molecules, with amino acids and proteins being major targets. Elevated levels of halogenated Tyr residues have been detected in proteins isolated from patients with atherosclerosis, asthma, and cystic fibrosis, implicating the production of HOX in these diseases. The quantitative significance of these findings requires knowledge of the kinetics of reaction of HOX with protein targets, and such data have not been previously available for HOBr. In this study, rate constants for reaction of HOBr with protein components have been determined. The second-order rate constants (22 degrees C, pH 7.4) for reaction with protein sites vary by 8 orders of magnitude and decrease in the order Cys > Trp approximately Met approximately His approximately alpha-amino > disulfide > Lys approximately Tyr > Arg > backbone amides > Gln/Asn. For most residues HOBr reacts 30-100 fold faster than HOCl, though Cys and Met residues are approximately 10-fold less reactive, and ring halogenation of Tyr is approximately 5000-fold faster. Thus, Tyr residues are more, and Cys and Met much less, important targets for HOBr than HOCl. Kinetic models have been developed to predict the targets of HOX attack on proteins and free amino acids. Overall, these results shed light on the mechanisms of cell damage induced by HOX and indicate, for example, that the 3-chloro-Tyr:3-bromo-Tyr ratio does not reflect the relative roles of HOCl and HOBr in disease processes.
KW - Amides
KW - Amino Acids
KW - Bromates
KW - Cell Survival
KW - Computer Simulation
KW - Cysteine
KW - Disulfides
KW - Humans
KW - Kinetics
KW - Methionine
KW - Models, Chemical
KW - Oxidative Stress
KW - Phagocytes
KW - Serum Albumin
KW - Tyrosine
U2 - 10.1021/bi035946a
DO - 10.1021/bi035946a
M3 - Journal article
C2 - 15096049
VL - 43
SP - 4799
EP - 4809
JO - Biochemistry
JF - Biochemistry
SN - 0006-2960
IS - 16
ER -
ID: 138273131