A possible interaction between acetylcholinesterase and dopamine molecules during autoxidation of the amine.
Acetylcholinesterase has an action in the central nervous system, independent of hydrolysis of acetylcholine. This study explored the possible interaction between the two molecules: the effects of acetylcholinesterase on the autoxidation of the catecholamine were tested, and, in turn, modification of the catalytic activity of the enzyme by products of dopamine oxidation were studied. Acetylcholinesterase selectively inhibited the speed of quinone production from dopamine as well as accumulation of hydrogen peroxide, whilst the rate of generation of superoxide was increased. Analysis of absorption spectra revealed the formation of a new product, which appeared after mixing acetylcholinesterase and dopamine in neutral pH. In all cases, butyrylcholinesterase was ineffective. Incubation of acetylcholinesterase in the presence of dopamine resulted in a significant decrease in the catalytic activity of the enzyme. The effects of application of preparations modifying autoxidation of dopamine (SOD, catalase, peroxidase) suggested that inactivation of the enzyme occurred as a result of the direct interaction of a quinone and/or semiquinone oxidation product with enzyme, as opposed to any effects of reactive oxygen species. Because acetylcholinesterase and dopamine are co-released from the neurons degenerating in Parkinson's disease, a direct chemical interaction between these two molecules could have significance both for the normal functioning of the substantia nigra and for related pathological states.
Klegeris
A
A
University Department of Pharmacology, Oxford, UK.
Korkina
L G
LG
Greenfield
S A
SA
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D016227:Benzoquinones / Q000378:metabolism; D002091:Butyrylcholinesterase / Q000378:metabolism; D002374:Catalase / Q000494:pharmacology; D002417:Cattle; D002800:Cholinesterase Inhibitors; D004298:Dopamine / Q000378:metabolism* / Q000494:pharmacology; D005609:Free Radicals; D006861:Hydrogen Peroxide / Q000378:metabolism; D007700:Kinetics; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000494:pharmacology; D013053:Spectrophotometry; D013482:Superoxide Dismutase / Q000494:pharmacology
D016227:Benzoquinones; D002800:Cholinesterase Inhibitors; D005609:Free Radicals; C004532:quinone; D006861:Hydrogen Peroxide; D002374:Catalase; D009195:Peroxidase; D013482:Superoxide Dismutase; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; D004298:Dopamine