β-Methylamino-L-alanine
Names | |
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IUPAC name
3-(Methylamino)-L-alanine
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Systematic IUPAC name
(2S)-2-Amino-3-(methylamino)propanoic acid[1] | |
Other names
2-Amino-3-methylaminopropanoic acid
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Identifiers | |
3D model (
JSmol ) |
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ChEBI | |
ChEMBL | |
ChemSpider | |
KEGG | |
MeSH | alpha-amino-beta-methylaminopropionate |
PubChem CID
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UNII | |
CompTox Dashboard (EPA)
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Properties | |
C4H10N2O2 | |
Molar mass | 118.136 g·mol−1 |
log P | −0.1 |
Acidity (pKa) | 1.883 |
Basicity (pKb) | 12.114 |
Related compounds | |
Related alkanoic acids
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Related compounds
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Dimethylacetamide |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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β-Methylamino-L-alanine, or BMAA, is a
Structure and properties
BMAA is a derivative of the amino acid alanine with a methylamino group on the side chain. This non-proteinogenic amino acid is classified as a polar base.
Sources and detection
BMAA is produced by
High concentrations (144 to 1836 ng/mg of flesh) of BMAA are present in shark fins.
Neurotoxicity
BMAA can cross the blood–brain barrier in rats. It takes longer to get into the brain than into other organs, but once there, it is trapped in proteins, forming a reservoir for slow release over time.[14][15]
Mechanisms
Although the mechanisms by which BMAA causes motor neuron dysfunction and death are not entirely understood, current research suggests that there are multiple mechanisms of action. Acutely, BMAA can act as an
BMAA can be misincorporated into nascent proteins in place of
Effects
A study performed in 2015 with vervet monkeys (Chlorocebus sabaeus) in St. Kitts, which are homozygous for the apoE4 gene (a condition which in humans is a risk factor for Alzheimer's disease), found that vervets that were administered BMAA orally developed hallmark histopathology features of Alzheimer's disease, including amyloid beta plaques and neurofibrillary tangle accumulation. Vervets in the trial fed smaller doses of BMAA were found to have correlative decreases in these pathology features. Additionally, vervets that were co-administered BMAA with serine were found to have 70% less beta-amyloid plaques and neurofibrillary tangles than those administered BMAA alone, suggesting that serine may be protective against the neurotoxic effects of BMAA.
This experiment represents the first in-vivo model of Alzheimer's disease that features both beta-amyloid plaques and hyperphosphorylated tau protein. This study also demonstrates that BMAA, an environmental toxin, can trigger neurodegenerative disease as a result of a gene-environment interaction.[20]
Degenerative locomotor diseases have been described in animals grazing on
- limb muscle atrophy
- nonreactive degeneration of anterior horn cells
- degeneration and partial loss of pyramidal neurons of the motor cortex
- behavioral dysfunction
- conduction deficits in the central motor pathway
- neuropathological changes of motor cortex Betz cells
There are reports that low BMAA concentrations can selectively kill cultured motor neurons from mouse spinal cords and produce reactive oxygen species.[17][22]
Scientists have also found that newborn rats treated with BMAA show a progressive neurodegeneration in the hippocampus, including intracellular fibrillar inclusions, and impaired learning and memory as adults.[23][24][25] BMAA has been reported to be excreted into rodent breast milk, and subsequently transferred to the suckling offspring, suggesting mothers' and cows' milk might be other possible exposure routes.[26]
Human cases
This section is missing information about dosage exposed to -- to help contextualize risk.(September 2023) |
Chronic dietary exposure to BMAA is now considered to be a cause of the
In addition to eating traditional food items from cycad flour directly, BMAA may be ingested by humans through
Studies on human brain tissue of ALS/PDC, ALS, Alzheimer's disease, Parkinson's disease, Huntington's disease, and neurological controls indicated that BMAA is present in non-genetic progressive neurodegenerative disease, but not in controls or genetic-based Huntington's disease.[35][36][37][38]
As of 2021[update] research into the role of BMAA as an environmental factor in neurodegenerative disease continued.[39][40][41]
Clinical trials
Safe and effective ways of treating ALS patients with L-serine that has been found to protect non-human primates from BMAA-induced neurodegeneration, have been goals of clinical trials conducted by the Phoenix Neurological Associates and the Forbes/Norris ALS/MND clinic and sponsored by the Institute for Ethnomedicine.[42][43]
See also
- Oxalyldiaminopropionic acid, a related toxin
References
- ^ "alpha-amino-beta-methylaminopropionate - Compound Summary". PubChem Compound. USA: National Center for Biotechnology Information. 19 August 2005. Identification. Retrieved 25 April 2012.
- PMID 15809446.
- PMID 18538391.
- PMID 21704054.
- S2CID 248248698.
- S2CID 238249735.
- .
- S2CID 38943437.
- PMID 24349504.
- PMID 23660330.
- PMID 22412816.
- Science Daily. February 23, 2012.
- PMID 22421821.
- ^ Mash D, et al. Neurotoxic non-protein amino acid BMAA in brain from patients dying with ALS and Alzheimer's disease[permanent dead link] poster presented at: American Academy of Neurology Annual Meeting, Chicago, IL, 17 April 2008 Neurology 2008;70(suppl 1):A329.
- ^ Xie X, et al. Tracking brain uptake and protein incorporation of cyanobacterial toxin BMAA abstract presented at: 22nd Annual Symposium on ALS/MND, Sydney, Australia, 1 December 2011.
- S2CID 140209787.
- ^ PMID 17098435.
- S2CID 27441543.
- PMID 24086518.
- PMID 26791617.
- PMID 3107939.
- S2CID 24543858.
- PMID 24798087.
- PMID 19692667.
- ^ Karlsson, O. (2011). Distribution and Long-term Effects of the Environmental Neurotoxin β-N-methylamino-L-alanine (BMAA): Brain changes and behavioral impairments following developmental exposure. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-140785
- PMID 24194910.
- S2CID 12044484.
- ^ S2CID 44801930.
- S2CID 24248686.
- .
- S2CID 31799259.
- PMID 33862930
- PMID 16457975.
- PMID 33129020.
- PMID 15295100.
- S2CID 32474959.
- S2CID 25385417.
- S2CID 41622254.
- PMID 22069578.
- PMID 22382274.
- PMID 33547590.
- ^ Determining the Safety of L-serine in ALS.
- ^ Safety Study of High Doses of Zinc in ALS Patients (completed).