Urate as a Physiological Substrate for Myeloperoxidase

Meotti, Flávia Carla; Jameson, Guy N. L.; Turner, Rufus; Harwood, D. Tim; Stockwell, Samantha; Rees, Martin D.; Thomas, Shane R.; Kettle, Anthony J.

doi:10.1074/jbc.m110.172460

Cited by 114 publications

(78 citation statements)

References 83 publications

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“…Urate Oxidation by LPO in the Presence of Superoxide-Previously, it was shown that when MPO oxidizes urate in the presence of superoxide, a hydroperoxide is formed by the addition of superoxide to the urate radical (23). To determine how effective LPO is at producing urate hydroperoxide, urate was oxidized by LPO in the presence of hydrogen peroxide and superoxide generated by xanthine oxidase and acetaldehyde.…”

Section: Reaction Of Lpo With Urate and Identification Of The Reactionmentioning

confidence: 99%

“…Products by Mass Spectrometry-Oxidation of urate by LPO and hydrogen peroxide was demonstrated by showing a decrease in absorbance at 290 nm and a corresponding increase at 315 nm due to formation of products as reported previously for MPO (23). Urate is known to readily photolyze (49), so precautions were made to minimize this by utilizing reduced light intensity.…”

Section: Reaction Of Lpo With Urate and Identification Of The Reactionmentioning

confidence: 99%

“…The rate constants of the reactions of LPO compound I and II with urate were determined as described previously for urate oxidation by myeloperoxidase (23). Final concentrations were 1 M ferric LPO, 1 M hydrogen peroxide, and various concentrations of urate (0 -25 M).…”

Section: Reaction Of Lpo With Urate and Identification Of The Reactiomentioning

confidence: 99%

“…The samples were suspended in 20% ammonium acetate buffer, pH 6.8, and 80% acetonitrile and centrifuged for 1 min at 16,000 ϫ g. Urate, allantoin, and other intermediates were detected by liquid chromatography with mass spectrometry (LC/MS) as published previously (23). The urate oxidation products were monitored as described before but with the minor alteration of the chromatography by shortening the re-equilibration to 7 min and changing the source temperature of the mass spectrometer to 500°C (23,39 Urate Oxidation by LPO in the Presence of Superoxide-To investigate the formation of urate hydroperoxides by xanthine oxidase and LPO, organic hydroperoxides were detected using a ferrous oxidation-xylenol orange (FOX) assay as described previously (23, 37, 40 -42 (43) was minimized by using a filter with a cut-off at 320 nm. It was previously shown that equimolar concentrations of hydrogen peroxide were required to form the maximum amount of LPO compound I (29).…”

Section: Reaction Of Lpo With Urate and Identification Of The Reactiomentioning

confidence: 99%

“…Indeed, it was shown early that mammalian peroxidases oxidize urate to allantoin (21,22). Recently, kinetic studies by us revealed urate to be a physiological substrate for the neutrophil enzyme myeloperoxidase (MPO) 3 (23). It has also been suggested to be a substrate for the peroxidase cycle of prostaglandin synthase (24).…”

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confidence: 99%

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Uric Acid and Thiocyanate as Competing Substrates of Lactoperoxidase

Seidel

Parker

Turner

et al. 2014

Journal of Biological Chemistry

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Section: Reaction Of Lpo With Urate and Identification Of The Reactionmentioning

confidence: 99%

Section: Reaction Of Lpo With Urate and Identification Of The Reactionmentioning

confidence: 99%

Section: Reaction Of Lpo With Urate and Identification Of The Reactiomentioning

confidence: 99%

Section: Reaction Of Lpo With Urate and Identification Of The Reactiomentioning

confidence: 99%

mentioning

confidence: 99%

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Uric Acid and Thiocyanate as Competing Substrates of Lactoperoxidase

Seidel

Parker

Turner

et al. 2014

Journal of Biological Chemistry

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Biological Chemistry of Reactive Oxygen Species

Winterbourn

2012

Encyclopedia of Radicals in Chemistry, Biology and Materials

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Living organisms are continually exposed to free radicals and other reactive oxygen species as a result of metabolizing oxygen and other redox‐active compounds. Excessive production can result in biological damage, whereas in other situation, specific oxidants are generated as a host defense mechanism or as a cell signal that activates gene expression and metabolic responses. This article provides an overview of the specific reactive oxygen species that are generated biologically, how and where they arise, and their chemical reactivity with biological molecules.

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Are either or both hyperuricemia and xanthine oxidase directly toxic to the vasculature? A critical appraisal

Neogi

George²,

Rekhraj³

et al. 2012

Arthritis & Rheumatism

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Basic research and clinical studies have implicated a role for hyperuricemia and for xanthine oxidoreductase (XOR), the enzyme that generates uric acid (UA), in not only gout but also vascular diseases. At present, asymptomatic hyperuricemia (i.e., in the absence of gout, urate nephrolithiasis, or tumor lysis syndrome) is not an indication for therapy. With the rise over the past several decades in prevalence of both gout and hyperuricemia, clarifying the potential adverse effects of hyperuricemia (in patients with and without gout) is of public health importance. UA is not simply an inert end-product of purine metabolism in humans, but rather has potential antioxidant, pro-oxidant, and pro-inflammatory effects. However controversy remains as to which, if any, of these effects are of clinical relevance in development and complications of human vascular diseases in gout and asymptomatic hyperuricemia. Clearly, not all individuals with hyperuricemia develop gout, and studies to date have also been unable to clarify in which subjects hyperuricemia may have detrimental effects on the vasculature. Further, studies of urate-lowering therapy with XOR inhibition or uricosuric agents have not been able to definitively identify whether any such effects may be mediated by UA versus XO. Adequately sized, prospective randomized clinical trials of sufficient duration, and employing appropriate biomarkers, now appear critical to resolve the putative toxic roles of UA and XO in the human arterial circulation.

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Urate as a Physiological Substrate for Myeloperoxidase

Cited by 114 publications

References 83 publications

Uric Acid and Thiocyanate as Competing Substrates of Lactoperoxidase

Uric Acid and Thiocyanate as Competing Substrates of Lactoperoxidase

Biological Chemistry of Reactive Oxygen Species

Are either or both hyperuricemia and xanthine oxidase directly toxic to the vasculature? A critical appraisal

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