On the differential roles of Mg(2+), Zn(2+,) and Cu(2+) in the equilibrium of β-N-methyl-amino-L-alanine (BMAA) and its Carbamates
| Autor: | Viswanathan V Krishnan, Pedro Diaz-parga, Joy J. Goto |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
inorganic chemicals
0301 basic medicine Circular dichroism Carbamate Magnetic Resonance Spectroscopy Stereochemistry BMAA Bicarbonate Chemical structure medicine.medical_treatment Clinical Sciences Toxicology Article Nuclear magnetic resonance Divalent Adduct 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Molecule Magnesium Amino Acids Diamino chemistry.chemical_classification Alanine Neurology & Neurosurgery Cyanobacteria Toxins General Neuroscience Circular Dichroism Neurosciences Amino Acids Diamino Divalent metal ions Zinc 030104 developmental biology Carbamate formation chemistry Exchange spectroscopy Biochemistry and Cell Biology Carbamates 030217 neurology & neurosurgery Copper |
| Zdroj: | Neurotox Res Neurotoxicity research, vol 39, iss 1 |
| Popis: | β-N-methyl-amino-L-alanine (BMAA) in the presence of bicarbonate (HCO(3)−) undergoes structural modifications generating two carbamate species, α-carbamate and β-carbamate forms of BMAA. The chemical structure of BMAA and BMAA-carbamate adducts strongly suggest they may interact with divalent metal ions. The ability of BMAA to cross the blood-brain barrier and possibly interact with divalent metal ions may augment the neurotoxicity of these molecules. To understand the effects of divalent metal ions (Mg(2+), Zn(2+), and Cu(2+)) on the overall dynamic equilibrium between BMAA and its carbamate adducts, a systematic study using nuclear magnetic resonance (NMR) is presented. The chemical equilibria between BMAA, its carbamate adducts, and each of the divalent ions were studied using two-dimensional chemical exchange spectroscopy (EXSY). The NMR results demonstrate that BMAA preferentially interacts with Zn(2+) and Cu(2+), causing an overall reduction in the production of carbamate species by altering the dynamic equilibria. The NMR based spectral changes due to the BMAA interaction with Cu(2+) is more drastic than with the Zn(2+), under the same stoichiometric ratios of BMAA and the individual divalent ions. However, the presence of Mg(2+) does not significantly alter the dynamic equilibria between BMAA and its carbamate adducts. The NMR based results are further validated using circular dichroism (CD) spectroscopy observing the n→π interaction in the complex formation of BMAA and the divalent metal ions with additional verification of the interaction with Cu(2+), using UV-vis spectroscopy. Our results demonstrate that BMAA differentially interacts with divalent metal ions (Mg(2+) < Zn(2+) < Cu(2+)), and thus alters the rate of formation of carbamate products. The equilibria between BMAA, the bicarbonate ions, and the divalent metal ions may alter the total population of a specific form of BMAA-ion complex at physiological conditions and, therefore, adds a level of complexity of the mechanisms by which BMAA acts as a neurotoxin. |
| Databáze: | OpenAIRE |
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