Chemistry of Natural Non-Protein Amino Acids

植物的每一部分都含有超过35，000种不同的植物化学物质，其中绝大多数是次级或特殊的代谢产物，尚未得到确认。平均一杯咖啡含有约8,400种不同的phtyochemicals，而蔓越莓约有28,000种，一片叶子可多达40000种。在这些样本中，只有大约1,100种植物化学物质被完全鉴定出来。我们估计，一个普通人的饮食中每天含有超过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度和精度，但也可能产生误导或错误的结果。我的研究是用质谱法分析植物化学物质。我的HQP积极参与开发准确、有效的分析方法和统计工具，以实现准确的鉴定和定量。 拟议的研究计划将继续我们的一套非蛋白质氨基酸的调查所产生的蓝藻水华和积累通过生态系统和食物网。N-β-甲基氨基-L-丙氨酸（BMAA）是一种神经毒性非蛋白质氨基酸，自20世纪60年代以来就已为人所知，最近被认为是肌萎缩侧索硬化症（ALS）和其他进行性神经退行性疾病的潜在致病因子。BMAA是由湖泊和海洋中的藻类大量繁殖产生的，通过与某些植物的自然联系、用受污染的沃茨灌溉作物或通过生态系统的营养水平积累而进入食物链。例如，关岛的蓝细菌产生的BMAA是由苏铁树的种子、以苏铁种子为食的动物以及食用动物和苏铁种子制成的面粉的人积累的。关岛土著居民查莫罗人由于接触其传统食物网中的溴甲基苯丙胺，患上了神经变性疾病，症状类似于肌萎缩侧索硬化症、阿尔茨海默病和帕金森病。了解BMAA是如何产生和积累的，对于认识和尽量减少人类接触风险至关重要。 我的HQP开发方法来检测和量化BMAA和其他潜在的神经毒性非蛋白质氨基酸在生态系统和食物网。到目前为止，我们已经开发了准确的方法，并调查了包括加拿大在内的6个国家的天然食物生态系统，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。我们拟议的研究计划将通过减少食物链中天然存在的毒素来提高食品安全性，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--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.