Chemistry of non-protein amino acids

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The human diet is made up almost entirely of plants or animals that consumed plants and plant chemistry affects human health in several ways. Plants are the source of vitamins, nutrients and antioxidants that are essential to good health but an average leaf contains up to 30,000 distinct chemicals and virtually nothing is known about the vast majority of these. Beta-methylamino-L-alanine (BMAA) is a naturally-occurring non-protein amino acid that was originally discovered in cycad seeds and is produced by cyanobacteria that live in symbiosis with plants or are free living in fresh water or marine environments. The 'BMAA Hypothesis' postulated that BMAA could accumulate from cyanobacteria to plants to the animals that feed on the plants and to people who eat the plants and animals and that high exposures to BMAA may induce progressive neurodegenerative diseases such as ALS or Alzheimer's Disease. BMAA was originally described in studies to understand an epidemic of progressive neurodegenerative disease in Guam and BMAA accumulation has been demonstrated in various food webs including the traditional diet of the Chamorro people of Guam, as well as blue crabs, shrimp and fish of South Florida, oysters and fish of the Baltic Sea, and shark fins from the Atlantic. However, different labs have reported remarkably very different results in studies to identify and quantify BMAA in cyanobacteria, foods and human tissues leading to controversy that complicates data interpretation and must be resolved before the BMAA hypothesis can be fully tested. We are proposing a detailed analytical study that will provide validated methods and tools for monitoring of food chains and environmental samples and will determine the mechanism and conditions of BMAA production by cyanobacteria. Together, these studies are the first important steps toward evaluating the BMAA hypothesis and potentially toward understanding neurodegenerative disease.