알파-아미노-베타-메틸아미노프로피오네이트

3-(Methylamino)-(DL)-aniline was detected in the brain tissues of eight of nine Canadian Alzheimer's patients, but not detected in the brain tissues of 14 other Canadians who died of causes unrelated to neurodegeneration(1). 3-(Methylamino)-(DL)-aniline was found in the brain tissues of Chamorros who died of amyotropic lateral sclerosis or parkinsonism-dementia complex, but not in patients who died of causes unrelated to neurodegenerative disease(1).

Determination of the environmental factors involved in neurodegenerative diseases has been elusive. Methylmercury and beta-N-methylamino-L-alanine (BMAA) have both been implicated in this role. Exposure of primary cortical cultures to these compounds independently induced concentration-dependent neurotoxicity. Importantly, concentrations of BMAA (10-100 uM) that caused no toxicity alone potentiated methylmercury (3 uM) toxicity. In addition, concentrations of BMAA and methylmercury that had no effect by themselves on the main cellular antioxidant glutathione together decreased glutathione levels. Furthermore, the combined toxicity of methylmercury and BMAA was attenuated by the cell permeant form of glutathione, glutathione monoethyl ester. The results indicate a synergistic toxic effect of the environmental neurotoxins BMAA and methylmercury, and that the interaction is at the level of glutathione depletion. /beta-N-methylamino-L-alanine/

TERRESTRIAL FATE: Based on a classification scheme(1), an estimated Koc value of 1.8(SRC), determined from a structure estimation method(2), indicates that 3-(methylamino)-(DL)-alanine is expected to have very high mobility in soil(SRC). Estimated pKa values of 3-(methylamino)-(DL)-alanine are 1.16, 6.47 and 10.47(3), indicating that this compound will partially exist in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4). Volatilization of 3-(methylamino)-(DL)-alanine from moist soil surfaces is not expected to be an important fate process(SRC) given its pKa values(3) and estimated Henry's Law constant of 3.4X10-13 atm-cu m/mole(SRC), using a fragment constant estimation method(5). 3-(Methylamino)-(DL)-alanine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.9X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(6).

AQUATIC FATE: Based on a classification scheme(1), an estimated Koc value of 1.8(SRC), determined from a structure estimation method(2), indicates that 3-(methylamino)-(DL)-alanine is not expected to adsorb to suspended solids and sediment(SRC). Volatilization of neutral 3-(methylamino)-(DL)-alanine from water surfaces is not expected(3) based upon an estimated Henry's Law constant of 3.4X10-13 atm-cu m/mole(SRC), developed using a fragment constant estimation method(4). Estimated pKa values of 1.16, 6.47 and 10.47(5) indicate that 3-(methylamino)-(DL)-alanine will exist partially in the cation form at pH values of 5 to 9 and, therefore, volatilization from water surfaces of the ion is not expected to be an important fate process(SRC). According to a classification scheme(6), an estimated BCF of 3(SRC), from an estimated log Kow of -4.0(7) and a regression-derived equation(8), suggests the potential for bioconcentration in aquatic organisms is low(SRC). However studies have demonstrated a 10,000 fold biomagnification of free 3-(methylamino)-(DL)-alanine and a 50 fold biomagnification of total 3-(methylamino)-(DL)-alanine(9).

ATMOSPHERIC FATE: According to a model of gas/particle partitioning of semivolatile organic compounds in the atmosphere(1), 3-(methylamino)-(DL)-alanine, which has an estimated vapor pressure of 3.9X10-9 mm Hg at 25 °C(SRC), determined from a fragment constant method(2), is expected to exist solely in the particulate phase in the ambient atmosphere. Particulate-phase 3-(methylamino)-(DL)-alanine may be removed from the air by wet or dry deposition(SRC). 3-(Methylamino)-(DL)-alanine does not contain chromophores that absorb at wavelengths >290 nm(3) and, therefore, is not expected to be susceptible to direct photolysis by sunlight(SRC).

Using a structure estimation method based on molecular connectivity indices(1), the Koc of 3-(methylamino)-(DL)-alanine can be estimated to be 1.8(SRC). According to a classification scheme(2), this estimated Koc value suggests that 3-(methylamino)-(DL)-alanine is expected to have very high mobility in soil. Estimated pKa values of 1.16, 6.47 and 10.47(3) indicates that 3-(methylamino)-(DL)-alanine will exist partially in cation form in the environment and cations generally adsorb more strongly to soils containing organic carbon and clay than their neutral counterparts(4).

3-(Methylamino)-(L)-alanine was shown to be produced by members of the genera Microcystis, Anabaena, Planktothrix, Hapalosiphon, Anabaenopsis and Nostoc and may be produced by any cyanobacterial symbionts or free-living cyanobacteria(1).

3-(Methylamino)-(L)-alanine is found in seeds of Cycas circinalis /Queen Sago/.

/SURVEILLANCE/ The investigators/ tested the brain tissues of the Chamorro people of Guam who died of amyotrophic lateral sclerosis/Parkinsonism dimentia complex (ALS/PDC) for the neurotoxin beta-methylamino-l-alanine (BMAA). /The investigators/ used validated high-pressure liquid chromatography and liquid chromatography-mass spectrometry analyses to test well-characterized archival tissues of the superior frontal gyrus from eight Chamorros from Guam and a comparison group of 15 Canadians. BMAA was found as a free amino acid in 83% of Chamorro ALS/PDC patients (3-10 ug/g) as a protein-associated amino acid in 100% of the Chamorro individuals (149-1190 ug/g). Both forms of BMAA were also found at comparable levels in two Canadians who died of progressive neurodegenerative disease. ... /Beta-methylamino-l-alanine/

/SURVEILLANCE/ The aim of this study was to screen for and quantify the neurotoxic amino acid beta-N-methylamino-L-alanine (BMAA) in a cohort of autopsy specimens taken from Alzheimer's disease (AD), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and non-neurological controls. BMAA is produced by cyanobacteria found in a variety of freshwater, marine, and terrestrial habitats. The possibility of geographically broad human exposure to BMAA had been suggested by the discovery of BMAA in brain tissues of Chamorro patients with ALS/Parkinsonism dementia complex from Guam and more recently in AD patients from North America. These observations warranted an independent study of possible BMAA exposures outside of the Guam ecosystem. Postmortem brain specimens were taken from neuropathologically confirmed cases of 13 ALS, 12 AD, 8 HD patients, and 12 age-matched non-neurological controls. BMAA was quantified using a validated fluorescent HPLC method previously used to detect BMAA in patients from Guam. Tandem mass spectrometric (MS) analysis was carried out to confirm the identification of BMAA in neurological specimens. BMAA /was detected and quantified/ in neuroproteins from postmortem brain tissue of patients from the United States who died with sporadic AD and ALS but not HD. Incidental detections observed in two out of the 24 regions were analyzed from the controls. The concentrations of BMAA were below what had been reported previously in Chamarro ALS/ Parkinsonism dementia complex patients, but demonstrated a two-fold range across disease and regional brain area comparisons. The presence of BMAA in these patients was confirmed by triple quadrupole liquid chromatography/mass spectrometry/mass spectrometry. The occurrence of BMAA in North American ALS and AD patients suggests the possibility of a gene/environment interaction, with BMAA triggering neurodegeneration in vulnerable individuals. /beta-N-methylamino-L-alanine/

/SURVEILLANCE/ Cyanobacteria produce many neurotoxins including beta-methylamino-L-alanine (BMAA) that has been liked to amyotrophic lateral sclerosis (ALS) and neurodegenerative disease. A number of ALS cases have been diagnosed among residents of Enfield, NH, a town encompassing a lake with a history of cyanobacteria algal blooms. To investigate an association between toxic cyanobacterial blooms in New Hampshire and development of ALS, we reviewed records from our institution and other community databases to obtain demographic information on patients diagnosed with ALS within New England. ... Nine ALS patients who lived near Lake Mascoma in Enfield, NH, an incidence of sporadic ALS that is 10 to 25 times the expected incidence of 2/100,000/year /were identified/. /The investigators/ suggest that the high incidence of ALS in this potential cluster could be directly related to chronic exposure to cyanobacterial neurotoxins such as BMAA. Possible routes of toxin exposure include inhalation of aerosolized toxins, consuming fish, or ingestion of lake water. ... /beta-methylamino-L-alanine/

Concentrations of 3-(methylamino)-(DL)-alanine(BMAA) were reported in sea life from Florida waters(1).

Concentrations of 3-(methylamino)-(DL)-alanine(BMAA) were reported in sea life from Florida waters(1).

3-(Methylamino)-(DL)-alanine concentrations in shark fins of seven species common in South Florida coastal waters(1).[Table#4613]

Concentrations of 3-(methylamino)-(DL)-alanine(BMAA) were reported in sea life from Florida waters(1).

3-(Methylamino)-(DL)-alanine is soluble in water and has a low Kow, therefore it would not be expected to biomagnify up the food chain(1). An estimated BCF of 3 was calculated in fish for 3-(methylamino)-(DL)-alanine(SRC), using an estimated log Kow of -4.0(2) and a regression-derived equation(3). According to a classification scheme(4), this BCF suggests the potential for bioconcentration in aquatic organisms is low(SRC). However studies have demonstrated a 10,000 fold biomagnification of free 3-(methylamino)-(DL)-alanine and a 50 fold biomagnification of total 3-(methylamino)-(DL)-alanine(1).

The Henry's Law constant for 3-(methylamino)-(DL)-alanine is estimated as 3.4X10-13 atm-cu m/mole(SRC) using a fragment constant estimation method(1). Estimated pKa values of 1.16, 6.47 and 10.47(2) indicate that 3-(methylamino)-(DL)-alanine will exist partially in the cation form at pH values of 5 to 9(SRC). This Henry's Law constant and estimated pKa values indicate that 3-(methylamino)-(DL)-alanine is expected to be essentially nonvolatile from moist soil and water surfaces(3). 3-(Methylamino)-(DL)-alanine is not expected to volatilize from dry soil surfaces(SRC) based upon an estimated vapor pressure of 3.9X10-9 Hg(SRC), determined from a fragment constant method(4).

3-(Methylamino)-(DL)-alanine was shown to be produced by members of the genera Microcystis, Anabaena, Planktothrix, Hapalosiphon, Anabaenopsis and Nostoc and may be produced by any cyanobacterial symbionts or free-living cyanobacteria.

3-(Methylamino)-(l)-alanine is found in seeds of Cycas circinalis /Queen Sago/.