Chloramines as intermediates of oxidation reaction of amino acids by myeloperoxidase

Zgliczyński, J.M.; Stelmaszyńska, Teresa; Domański, Jerzy; Ostrowski, W.

doi:10.1016/0005-2744(71)90281-6

Cited by 250 publications

(100 citation statements)

References 9 publications

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“…The major product of myeloperoxidase at plasma concentrations of chloride ion is hypochlorous acid (HOCl; 7,8): (1) This potent cytotoxin chlorinates electron rich substrates and oxidatively bleaches heme proteins, nucleotides and carotenoids (8)(9)(10)(11)(12). Indirect evidence suggests that reactive carbonyls form in proteins (13)(14)(15) and amino acids (16,17) exposed to myeloperoxidase-generated HOCl, and trace quantities of aldehydes have been detected in amino acids exposed to high concentrations of reagent HOCl under strongly acidic conditions (18). Neither the reaction pathways nor the physiological relevance of the products generated in these reactions have been clearly established.…”

Section: Introductionmentioning

confidence: 99%

Human neutrophils employ the myeloperoxidase-hydrogen peroxide-chloride system to convert hydroxy-amino acids into glycolaldehyde, 2-hydroxypropanal, and acrolein. A mechanism for the generation of highly reactive alpha-hydroxy and alpha,beta-unsaturated aldehydes by phagocytes at sites of inflammation.

et al. 1997

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Reactive aldehydes derived from reducing sugars and lipid peroxidation play a critical role in the formation of advanced glycation end (AGE) products and oxidative tissue damage. We have recently proposed another mechanism for aldehyde generation at sites of inflammation that involves myeloperoxidase, a heme enzyme secreted by activated phagocytes. We now demonstrate that human neutrophils employ the myeloperoxidase-H 2 O 2 -chloride system to produce ␣ -hydroxy and ␣ , ␤ -unsaturated aldehydes from hydroxy-amino acids in high yield. Identities of the aldehydes were established using mass spectrometry and high performance liquid chromatography. Activated neutrophils converted L -serine to glycolaldehyde, an ␣ -hydroxyaldehyde which mediates protein cross-linking and formation of N ⑀ -(carboxymethyl)lysine, an AGE product. L -Threonine was similarly oxidized to 2-hydroxypropanal and its dehydration product, acrolein, an extremely reactive ␣ , ␤ -unsaturated aldehyde which alkylates proteins and nucleic acids. Aldehyde generation required neutrophil activation and a free hydroxy-amino acid; it was inhibited by catalase and heme poisons, implicating H 2 O 2 and myeloperoxidase in the cellular reaction. Aldehyde production by purified myeloperoxidase required H 2 O 2 and chloride, and was mimicked by reagent hypochlorous acid (HOCl) in the absence of enzyme, suggesting that the reaction pathway involves a chlorinated intermediate. Collectively, these results indicate that the myeloperoxidase-H 2 O 2 -chloride system of phagocytes converts free hydroxy-amino acids into highly reactive ␣ -hydroxy and ␣ , ␤ -unsaturated aldehydes. The generation of glycolaldehyde, 2-hydroxypropanal, and acrolein by activated phagocytes may thus play a role in AGE product formation and tissue damage at sites of inflammation. ( J. Clin. Invest. 1997. 99:424-432.)

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Section: Introductionmentioning

confidence: 99%

Human neutrophils employ the myeloperoxidase-hydrogen peroxide-chloride system to convert hydroxy-amino acids into glycolaldehyde, 2-hydroxypropanal, and acrolein. A mechanism for the generation of highly reactive alpha-hydroxy and alpha,beta-unsaturated aldehydes by phagocytes at sites of inflammation.

et al. 1997

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“…It involves myeloperoxidase, a heme protein secreted by activated phagocytes (19). This enzyme uses H2O2, which phagocytes also secrete, to convert chloride ion to hypochlorous acid (HOCl) (19)(20)(21) The initial product of the myeloperoxidase-H 2 O 2 -chloride system, HOCl, reacts with the amino group (RNH 2 ) of free amino acids to form a chloramine (RNHCl) (19,(22)(23)(24)(25):…”

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confidence: 99%

“…3 ] that have both a carboxyl group and amino group on the α-carbon (26) then decompose to form an aldehyde (RCHO) (24)(25)(26)(27)(28):…”

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The myeloperoxidase system of human phagocytes generates Nε-(carboxymethyl)lysine on proteins: a mechanism for producing advanced glycation end products at sites of inflammation

Anderson¹,

Requena²,

Crowley³

et al. 1999

J. Clin. Invest.

327

219

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“…However, these products are not specific for the action of HOCl as other oxidants such as hydroxyl radicals and peroxyl radicals induce identical materials (39 -41). HOCl also reacts readily with the free amino group of amino acids and peptides either at the Nterminal position (21,42,43) or at the side chain (lysine) (44) to form an unstable chloramine; reaction has also been postulated to occur at backbone amide sites to give chloramides (26). Decomposition of such chloramines and chloramides leads to deamination, decarboxylation, or aldehyde formation depending on the nature of the chloramine involved (7,20,24,45,46).…”

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Reactions of Hypochlorous Acid with Tyrosine and Peptidyl-tyrosyl Residues Give Dichlorinated and Aldehydic Products in Addition to 3-Chlorotyrosine

Fu¹,

Wang²,

Davies³

et al. 2000

Journal of Biological Chemistry

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The toxicity of hypochlorous acid (HOCl) generated from activated neutrophils has been associated with several pathological processes such as atherosclerosis. Formation of 3-chlorotyrosine (Cl-Tyr) has been used as a marker for assessing the involvement of HOCl in such processes. In this study, we aimed to investigate the formation of Cl-Tyr from reaction of HOCl with tyrosine (both free and peptide-bound) and the fate of Cl-Tyr under such conditions. Tyrosine, N-acetyltyrosine, bovine serum albumin, and human low density lipoproteins were incubated with a range of reagent hypochlorite concentrations for varying periods in 10 mM phosphate buffer (pH 7.4) at 22°C. The reaction products, and several biological samples, were hydrolyzed (in the case of proteins), isolated, and purified by high pressure liquid chromatography and characterized or quantitated by mass spectrometry and NMR. A significant amount of 3,5-dichlorotyrosine (diCl-Tyr) was obtained from the bovine serum albumin, low density lipoprotein, and some biological samples, in addition to Cl-Tyr, indicating that Cl-Tyr competes effectively for HOCl even when tyrosine is present in great excess. Cl-Tyr and diCl-Tyr were also formed from free tyrosine but then reacted further with HOCl. This finding differs from a claim in the literature that Cl-Tyr was not formed in such a system. The further reaction products of ClTyr and diCl-Tyr with HOCl were elucidated as their corresponding mono-and dichlorinated 4-hydroxyphenylacetaldehydes. These results indicate the importance of assessing other products of HOCl action in addition to Cl-Tyr.

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Chloramines as intermediates of oxidation reaction of amino acids by myeloperoxidase

Cited by 250 publications

References 9 publications

The myeloperoxidase system of human phagocytes generates Nε-(carboxymethyl)lysine on proteins: a mechanism for producing advanced glycation end products at sites of inflammation

Reactions of Hypochlorous Acid with Tyrosine and Peptidyl-tyrosyl Residues Give Dichlorinated and Aldehydic Products in Addition to 3-Chlorotyrosine

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