Misincorporation of Beta-Methylamino-L-Alanine Into Protein: A Potential Mechanism for Motor Neuron Disease

Liu, Jenny
Journal Title
Journal ISSN
Volume Title
University of Hawaii at Manoa
Imagine living in an immobilized body, while being fully aware of your surroundings. This is the experience of many motor neuron disease afflicted patients, especially those with amyotrophic lateral sclerosis (ALS). ALS-Parkinsonism Dementia complex (ALS-PDC) is a form of ALS with an abnormally high incidence in members of certain ethnicities. An ethnobotanical connection to nutrition involving the cyanobacterial neurotoxin beta- methylamino-L-alanine (BMAA) has long been postulated. Specifically, incorporation of BMAA into human protein has been suggested to contribute significantly to the etiology of ALS-PDC. Using an in-vivo approach, this research project focused on determining whether BMAA is transformed into high molecular weight substances such as proteins. The uptake and metabolic fate of BMAA was followed within a prokaryotic model system, a cyanobacterium, during the logarithmic growth phase. Prokaryotes generally have higher error rates for the misincorporation of non-proteinogenic amino acids into protein than eukaryotes. Observation of BMAA in the protein fraction would therefore provide a first estimate of the potential significance of the misincorporation of BMAA in a eukaryotic system. Chemical analysis showed that about 1% of the initial amount of BMAA added to the cell culture was present within intracellular, hydrolyzable, low molecular weight compounds below 10 kilodaltons, and only 6 × 10-4 %, if any, was present in the high molecular mass, i.e. protein, form. This suggests that intracellular protein is not a primary reservoir of BMAA in this model system and, by extension, in eukaryotes, and that an unexpectedly large percentage of BMAA, 98%, is metabolized. Imagine living in an immobilized body, while being fully aware of your surroundings.
beta-methylamino-L-alanine (BMAA), misincorporation
Access Rights
Email libraryada-l@lists.hawaii.edu if you need this content in ADA-compliant format.