Chemistry of Natural Non-Protein Amino Acids

天然非蛋白质氨基酸的化学

• 批准号: RGPIN-2018-03883
• 负责人: Murch, Susan
• 金额: $ 5.25万
• 依托单位: University of British Columbia
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2022
• 资助国家: 加拿大
• 起止时间: 2022-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=761671
• 关键词: Chemistry; Natural; Non; Protein; Amino

Each piece of a plant contains > 35,000 distinct phytochemicals, and the vast majority of these are secondary or specialized metabolites that remain unidentified. An average cup of coffee has about 8,400 distinct phtyochemicals while a cranberry has about 28,000 and a piece of leaf can have up to 40,000. Only about 1,100 phytochemicals have been fully identified in any of these samples. We estimated that an average person's diet contains > 200,000 unknown phytochemicals per day. Recent advances in chromatography and mass spectrometry have enabled detection and quantification with greater accuracy and precision but can also give misleading or false results. My research uses mass spectrometry to analyze plant chemicals. My HQP are actively engaged in developing accurate validated analytical methods and statistical tools for accurate identification and quantification. The proposed research program will continue our investigation of a set of non-protein amino acids produced by cyanobacterial blooms and accumulated through ecosystems and food webs. N--methylamino-L-alanine (BMAA) is a neurotoxic non-protein amino acid that has been known since the 1960s and has recently been associated as a potential causal agent of amyotrophic lateral sclerosis (ALS) and other progressive neurodegenerative diseases. BMAA is produced by algal blooms in lakes and oceans where it enters food chain through natural associations with some plants, irrigation of crop plants with contaminated waters, or accumulation through trophic levels of ecosystems. For example, BMAA produced by cyanobacteria in Guam was accumulated by the seeds of cycad trees, the animals that fed on the cycad seeds and the humans who consumed both the animals and a flour made from cycad seeds. The indigenous population of Guam, the Chamorro, suffered from an epidemic of neurodegenerative disease with symptoms similar to ALS, Alzheimer's and Parkinson's diseases related to exposure BMAA in their traditional food web. Understanding how BMAA is produced and accumulated is essential to recognizing and minimizing the human risks of exposure.My HQP develop methods to detect and quantify BMAA and other potentially neurotoxic non-protein amino acids in ecosystems and food webs. To date, we have developed accurate methods and investigated natural food ecosystems in 6 countries including Canada, quantified BMAA in Lake Winnipeg and made significant progress in understanding the mechanisms of neurotoxicity. Our proposed research program will improve food safety through reduction of naturally-occurring toxins in the food chain and understand the chemistry, metabolism, and environmental importance of natural non-protein amino acids.

每块植物的植物含有> 35,000种不同的植物化学物质，其中绝大多数是二次或专门的代谢物，它们仍然不明。平均一杯咖啡有大约8,400个不同的磷酸化学物质，而蔓越莓的咖啡约为28,000，一块叶子可以拥有多达40,000。在这些样品中的任何一个中，只有大约1,100种植物化学物质被充分鉴定。我们估计，普通人的饮食每天含有> 20万名未知的植物化学物质。色谱和质谱法的最新进展已以更高的准确性和精确度实现了检测和定量，但也可能给出误导或错误的结果。我的研究使用质谱法来分析植物化学物质。我的HQP积极参与开发准确的验证分析方法和统计工具，以准确识别和定量。拟议的研究计划将继续我们研究由蓝细菌开花产生的一组非蛋白质氨基酸，并通过生态系统和食物网积累。 N-甲基氨基 - L-丙氨酸（BMAA）是一种神经毒性的非蛋白质氨基酸，自1960年代以来就一直知道，最近与肌萎缩性侧面硬化症（ALS）和其他进行性神经退行性疾病的潜在因果剂相关。 BMAA是由湖泊和海洋中的藻类开花产生的，它通过与某些植物的自然关联，被污染的水的作物灌溉或通过生态系统的营养水平积累而进入食物链。例如，蓝细菌在关岛产生的BMAA是由寿命树的种子，饲养在苏打种子上的动物以及食用动物的人类和用cycad种子制成的面粉的人类积累的。关岛的土著人口，夏诺罗（Chamorro），患有神经退行性疾病的流行病，其症状与ALS，阿尔茨海默氏症和帕金森氏症的疾病相似，与传统食物网络中的暴露BMAA有关。了解BMAA的产生和积累对于识别和最大程度地识别人类暴露的风险至关重要。我的HQP开发了在生态系统和食物网中检测和量化BMAA和其他潜在神经毒性非蛋白质氨基酸的方法。迄今为止，我们已经开发了准确的方法，并研究了包括加拿大在内的6个国家 /地区的天然食品生态系统，在温尼伯湖进行了量化BMAA，并在理解神经毒性机制方面取得了重大进展。我们提出的研究计划将通过减少食物链中的天然毒素来提高食品安全，并了解天然非蛋白质氨基酸的化学，代谢和环境重要性。