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首页> 外文期刊>Journal of biochemical and molecular toxicology >The Use of p-Aminobenzoic Acid as a Probe Substance for the Targeted Profiling of Glycine Conjugation
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The Use of p-Aminobenzoic Acid as a Probe Substance for the Targeted Profiling of Glycine Conjugation

机译：对氨基苯甲酸作为探针物质用于甘氨酸结合的靶向谱分析

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摘要

Glycine conjugation facilitates the metabolism of toxic aromatic acids, capable of disrupting mitochondrial integrity. Owing to the high exposure to toxic substrates, characterization of individual glycine conjugation capacity, and its regulatory factors has become increasingly important. Aspirin and benzoate have been employed for this purpose; however, adverse reactions, aspirin intolerance, and Reye's syndrome in children are substantial drawbacks. The goal of this study was to investigate p-aminobenzoic acid (PABA) as an alternative glycine conjugation probe. Ten human volunteers participated in a PABA challenge test, and p-aminohippuric acid (PAHA), p-acetamidobenzoic acid, and p-acetamidohippuric acid were quantified in urine. The glycine N-acyltransferase gene of the volunteers was also screened for two polymorphisms associated with normal and increased enzyme activity. All of the individuals were homozygous for increased enzyme activity, but excretion of PAHA varied significantly (16-56%, hippurate ratio). The intricacies of PABA metabolism revealed possible limiting factors and the potential of PABA as an indicator of Phase 0 biotransformation.
机译：甘氨酸结合促进有毒芳香酸的代谢，能够破坏线粒体的完整性。由于高剂量暴露于有毒底物，表征各个甘氨酸的结合能力及其调节因素变得越来越重要。阿司匹林和苯甲酸酯已被用于此目的。但是，儿童的不良反应，阿司匹林耐受性和瑞氏综合症是严重的缺点。这项研究的目的是研究对氨基苯甲酸（PABA）作为甘氨酸偶联探针的替代品。十名人类志愿者参加了PABA激发试验，对尿中的对氨基马尿酸（PAHA），对乙酰氨基苯甲酸和对乙酰氨基马尿酸进行了定量。还筛选了志愿者的甘氨酸N-酰基转移酶基因中与正常和增加的酶活性有关的两个多态性。所有这些个体都是纯合的，以增加酶的活性，但是PAHA的排泄变化很大（16-65％，马尿酸比率）。 PABA代谢的复杂性揭示了可能的限制因素以及PABA作为0期生物转化指标的潜力。

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