摘要
氧化应激在各种急性和慢性疾病的发病机制中起重要作用。氧化应激相关终端产品的测量可以执行,例如,生理对位酪氨酸结构异构体即元和邻位酪氨酸都是苯丙氨酸的氧化衍生物。最近的数据表明,在脓毒症中,元酪氨酸会提高血清水平,其高峰出现在第二到第三天(P<0.05对比控制组)。系统炎症的动力学强度与血清降钙素原水平有关。在一个类似的研究中,尿元酪氨酸排出量与每日胰岛素剂量和非脓毒症患者的胰岛素葡萄糖产出相关(P<0.01)。使用线性回归模型,转酪氨酸排泄物,尿元或对位酪氨酸,尿邻/对位酪氨酸以及尿(meta- + orthotyrosine)对位酪氨酸被证明是碳水化合物代谢标记物。 利用慢性动物模型,我们试图使用对酪氨酸、生理氨基酸来弥补异常酪氨酸异构体。大鼠用高胆固醇饮食标准喂养,并口服对酪氨酸或赋形剂。高胆固醇喂养导致主动脉壁间酪氨酸含量增加,降低了血管舒张主动脉胰岛素和胰高血糖素样肽-1类似物和利拉鲁肽,这两者都可以通过口服酪氨酸来预防。 最后,这些数据表明,元和邻位酪氨酸在急性疾病中是与氧化应激有关的潜在的氧化应激标志物,也可能干扰胰岛素感染人类的行动。竞争元和邻位酪氨酸的对位酪氨酸补充剂可能会产生氧化应激相关疾病的保护作用。
关键词: 元酪氨酸;酪氨酸邻位;酪氨酸对位;脓毒症;炎症;氧化应激;激素抵抗;糖代谢。
Current Medicinal Chemistry
Title:Role of Tyrosine Isomers in Acute and Chronic Diseases Leading to Oxidative Stress - A Review
Volume: 23 Issue: 7
Author(s): Gergő A. Molnár, Szilárd Kun, Eszter Sélley, Melinda Kertész, Lívia Szélig, Csaba Csontos, Katalin Böddi, Lajos Bogár and Attila Miseta, István Wittmann
Affiliation:
关键词: 元酪氨酸;酪氨酸邻位;酪氨酸对位;脓毒症;炎症;氧化应激;激素抵抗;糖代谢。
摘要: Oxidative stress plays a major role in the pathogenesis of a variety of acute and chronic diseases. Measurement of the oxidative stress-related end products may be performed, e.g. that of structural isomers of the physiological para-tyrosine, namely meta- and ortho-tyrosine, that are oxidized derivatives of phenylalanine. Recent data suggest that in sepsis, serum level of meta-tyrosine increases, which peaks on the 2nd and 3rd days (p<0.05 vs. controls), and the kinetics follows the intensity of the systemic inflammation correlating with serum procalcitonin levels. In a similar study subset, urinary meta-tyrosine excretion correlated with both need of daily insulin dose and the insulin-glucose product in non-diabetic septic cases (p<0.01 for both). Using linear regression model, meta-tyrosine excretion, urinary meta-tyrosine/para-tyrosine, urinary ortho-tyrosine/para-tyrosine and urinary (meta- + orthotyrosine)/ para-tyrosine proved to be markers of carbohydrate homeostasis.
In a chronic rodent model, we tried to compensate the abnormal tyrosine isomers using para-tyrosine, the physiological amino acid. Rats were fed a standard high cholesterol-diet, and were given para-tyrosine or vehicle orally. High-cholesterol feeding lead to a significant increase in aortic wall meta-tyrosine content and a decreased vasorelaxation of the aorta to insulin and the glucagon-like peptide-1 analogue, liraglutide, that both could be prevented by administration of para-tyrosine.
Concluding, these data suggest that meta- and ortho-tyrosine are potential markers of oxidative stress in acute diseases related to oxidative stress, and may also interfere with insulin action in septic humans. Competition of meta- and ortho-tyrosine by supplementation of para-tyrosine may exert a protective role in oxidative stress-related diseases.
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Gergő A. Molnár, Szilárd Kun, Eszter Sélley, Melinda Kertész, Lívia Szélig, Csaba Csontos, Katalin Böddi, Lajos Bogár and Attila Miseta, István Wittmann , Role of Tyrosine Isomers in Acute and Chronic Diseases Leading to Oxidative Stress - A Review, Current Medicinal Chemistry 2016; 23 (7) . https://dx.doi.org/10.2174/0929867323666160119094516
DOI https://dx.doi.org/10.2174/0929867323666160119094516 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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