Chemistry of Natural Non-Protein Amino Acids

植物的每一块都含有35,000种不同的植物化学物质，其中绝大多数是尚未确定的次生或特殊代谢物。一杯咖啡含有大约8400种不同的植酸物质，而一颗小红莓含有大约28000种不同的植酸化学物质，一片叶子含有多达4万种。在这些样本中，只有大约1100种植物化学物质被完全识别出来。我们估计，普通人的饮食中每天含有20万英镑的未知植物化学物质。层析和质谱学的最新进展使检测和定量具有更高的准确度和精密度，但也可能给出误导或错误的结果。我的研究使用质谱仪来分析植物化学物质。我的HQP积极参与开发准确、有效的分析方法和统计工具，以进行准确的识别和量化。 拟议的研究计划将继续我们对蓝藻水华产生并通过生态系统和食物网积累的一系列非蛋白质氨基酸的研究。N-甲氨基-L-丙氨酸(BMAA)是20世纪60年代发现的一种神经毒性非蛋白质氨基酸，近年来被认为是肌萎缩侧索硬化症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水华产生的，在那里它通过与一些植物的自然结合、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，关岛蓝藻产生的BMAA是通过苏铁树的种子积累的，以苏铁种子为食的动物和食用这些动物和由苏铁种子制成的面粉的人。关岛的土著居民查莫罗人患有神经退行性疾病的流行，其症状类似于ALS、阿尔茨海默氏症和帕金森氏症，与在其传统食物网中接触BMAA有关。了解BMAA是如何产生和积累的，对于识别和最大限度地减少人类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的BMAA和其他潜在的神经毒性非蛋白质氨基酸的方法。到目前为止，我们已经开发了准确的方法，并在包括加拿大在内的6个国家调查了天然食物生态系统，量化了温尼伯湖中的BMAA，并在了解神经毒性的机制方面取得了重大进展。我们建议的研究计划将通过减少食物链中自然产生的毒素来改善食品安全，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--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.