Noncompetitive inhibition by aluminum, scandium and yttrium of acetylcholinesterase from Electrophorus electricus.

Measurements of altered activity of soluble acetylcholinesterase from E. electricus electric organ by the inorganic cations aluminum, scandium and yttrium demonstrate that these ions are noncompetitive enzyme inhibitors. Al3+ inhibited enzyme activity at all substrate and inhibitor concentrations studied. Inhibition by Al3+ did not appear to be sensitive to the active site-specific, competitive ligand physostigmine or to calcium, a peripheral site-binding activator cation. Inhibition by another peripheral site-binding noncompetitive inhibitor, decamethonium, was not altered by Al3+. Al3+ appears thus to have interacted with a class of peripheral anionic sites on AChE distinct from the beta- or P1 peripheral anionic sites that bind Ca2+ and C-10 and may be a useful probe of a subclass of gamma- or P2-4 peripheral anionic sites. A possible mechanism for Al3+ neurotoxicity, via alterations of the enzymes of cholinergic neurotransmission, is also suggested.