Chemistry of Natural Non-Protein Amino Acids

每一片植物都含有大约35000种不同的植物化学物质，其中绝大多数是次生的或专门的代谢物，至今仍未被识别。一杯普通的咖啡含有大约8400种不同的植物化学物质，而蔓越莓含有大约28000种，一片叶子含有多达40000种。在这些样本中，只有大约1100种植物化学物质被完全鉴定出来。我们估计，一个普通人每天的饮食中含有20万种未知的植物化学物质。色谱法和质谱法的最新进展使检测和定量具有更高的准确性和精密度，但也可能产生误导或错误的结果。我的研究使用质谱分析植物化学物质。我的HQP积极致力于开发准确有效的分析方法和统计工具，以进行准确的鉴定和量化。******拟议的研究计划将继续我们对一组非蛋白氨基酸的调查，这些氨基酸由蓝藻华产生，并通过生态系统和食物网积累。N-β-甲氨基- l -丙氨酸（BMAA）是一种神经毒性的非蛋白质氨基酸，自20世纪60年代以来就被发现，最近被认为是肌萎缩性侧索硬化症（ALS）和其他进行性神经退行性疾病的潜在病因。BMAA是由湖泊和海洋中的藻华产生的，通过与某些植物的自然联系、用受污染的水灌溉农作物或通过生态系统的营养水平积累进入食物链。例如，关岛的蓝藻产生的BMAA是由苏铁树的种子、以苏铁树种子为食的动物以及既食用这些动物又食用苏铁树种子制成的面粉的人类积累的。关岛的土著居民查莫罗人患有一种流行的神经退行性疾病，其症状类似于ALS、阿尔茨海默病和帕金森病，这与他们在传统食物网中接触BMAA有关。了解BMAA是如何产生和积累的，对于认识和尽量减少人体暴露的风险至关重要。******我的HQP开发了检测和量化生态系统和食物网中BMAA和其他潜在神经毒性非蛋白氨基酸的方法。迄今为止，我们已经在加拿大等6个国家开发了准确的方法并调查了天然食品生态系统，量化了温尼伯湖的BMAA，并在了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自然产生的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。

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-β-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.