Metabolomic profiling of the effects of allopurinol on Drosophila melanogaster
Metabolomic profiling of the effects of allopurinol on Drosophila melanogaster
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DOI：
10.1007/s11306-011-0275-6
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发表时间：
2011-12-01
期刊：
影响因子：
3.6
通讯作者：
Watson, David G.
中科院分区：
文献类型：
--
作者：
Al Bratty, Mohammed;Hobani, Yahya;Watson, David G.
采用亲水相互作用色谱结合傅立叶变换质谱的方法研究黄嘌呤氧化酶抑制剂别嘌呤醇对野生型黑腹果蝇的影响。别嘌呤醇治疗表型模仿了玫瑰色突变，导致黄嘌呤和次黄嘌呤水平升高，尿酸和尿囊素水平下降。然而，治疗后还出现了一些意想不到的代谢变化。抗坏血酸水平检测不到，谷胱甘肽水平下降，谷胱甘肽二硫化物水平上升，蛋氨酸S-氧化物水平上升，核黄素水平下降。这种氧化应激的起源并不明显;但是，强烈提示其可能与NADPH水平下降相关，NADPH水平下降与葡萄糖-6-磷酸脱氢酶活性降低相关，导致戊糖磷酸途径中某些代谢物水平降低。除了产生氧化应激外，还对色氨酸代谢有显著影响，其中犬尿氨酸途径中的大多数代谢物被别嘌呤醇治疗降低。对犬尿氨酸途径的影响可能与别嘌呤醇治疗精神分裂症的既定用途有关。
Metabolomic profiling using hydrophilic interaction chromatography in combination with Fourier transform mass spectrometry was used to study the effects of the xanthine oxidase inhibitor allopurinol on wild type Drosophila melanogaster. Allopurinol treatment phenocopied the rosy mutation causing an elevation in the levels of xanthine and hypoxanthine and a fall in the levels of uric acid and allantoin. However, in addition there were some unexpected metabolic changes after treatment. Ascorbic acid levels were undetectable, glutathione levels fell and glutathione disulphide levels rose, methionine S-oxide levels rose and riboflavin levels fell. The origin of this oxidative stress was not immediately apparent; however, there was a strong suggestion that it might be related to a fall in NADPH levels linked to a reduction in glucose-6-phosphate dehydrogenase activity, resulting in reduced levels of some metabolites in the pentose phosphate pathway. In addition to producing oxidative stress there were marked effects on tryptophan metabolism with most of the metabolites in the kynurenine pathway being lowered by allopurinol treatment. The effects on the kynurenine pathway could be related to the established use of allopurinol in treating schizophrenia.