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卡比多巴和其他儿茶酚与过氧化物酶催化的反应的干扰。

Interference of carbidopa and other catechols with reactions catalyzed by peroxidases.

机构信息

Faculty of Chemistry, Opole University, Ul. Oleska 48, 45-052 Opole, Poland.

Advanced Analysis Center, National Agriculture and Food Research Organization (NARO), 2-1-2 Kannondai, Tsukuba, Ibaraki 305-8602, Japan.

出版信息

Biochim Biophys Acta Gen Subj. 2018 Jul;1862(7):1626-1634. doi: 10.1016/j.bbagen.2018.04.007. Epub 2018 Apr 9.

DOI:10.1016/j.bbagen.2018.04.007
PMID:29649511
Abstract

BACKGROUND

A number of compounds, including ascorbic acid, catecholamines, flavonoids, p-diphenols and hydrazine derivatives have been reported to interfere with peroxidase-based medical diagnostic tests (Trinder reaction) but the mechanisms of these effects have not been fully elucidated.

METHODS

Reactions of bovine myeloperoxidase with o-dianisidine, bovine lactoperoxidase with ABTS and horseradish peroxidase with 4-aminoantipyrine/phenol in the presence of carbidopa, an anti-Parkinsonian drug, and other catechols, including l-dopa, were monitored spectrophotometrically and by measuring hydrogen peroxide consumption.

RESULTS

Chromophore formation in all three enzyme/substrate systems was blocked in the presence of carbidopa and other catechols. However, the rates of hydrogen peroxide consumption were not much affected. Irreversible enzyme inhibition was also insignificant.

CONCLUSIONS

Tested compounds reduced the oxidation products or intermediates of model substrates thus preventing chromophore formation. This interference may affect interpretation of results of diagnostic tests in samples from patients with Parkinson's disease treated with carbidopa and l-dopa.

GENERAL SIGNIFICANCE

This mechanism allows prediction of interference in peroxidase-based diagnostic tests for other compounds, including drugs and natural products.

摘要

背景

已有报道称,包括抗坏血酸、儿茶酚胺、类黄酮、对二苯酚和联氨衍生物在内的许多化合物会干扰基于过氧化物酶的医学诊断测试(Trinder 反应),但这些影响的机制尚未完全阐明。

方法

在卡比多巴(一种抗帕金森病药物)和其他儿茶酚的存在下,监测牛髓过氧化物酶与邻二茴香胺、牛乳过氧化物酶与 ABTS 和辣根过氧化物酶与 4-氨基安替比林/苯酚的反应,通过分光光度法和测量过氧化氢消耗来进行。

结果

在卡比多巴和其他儿茶酚的存在下,所有三种酶/底物系统中的生色团形成均被阻断。然而,过氧化氢的消耗速率并没有受到太大影响。不可逆的酶抑制作用也不显著。

结论

测试化合物减少了模型底物的氧化产物或中间产物,从而阻止了生色团的形成。这种干扰可能会影响接受卡比多巴和左旋多巴治疗的帕金森病患者样本中诊断测试结果的解释。

一般意义

这种机制允许预测其他化合物(包括药物和天然产物)在基于过氧化物酶的诊断测试中的干扰。

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Biochim Biophys Acta Gen Subj. 2018 Jul;1862(7):1626-1634. doi: 10.1016/j.bbagen.2018.04.007. Epub 2018 Apr 9.
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