Methylmercury-cholinesterase interactions in rats

Area of Science:

• Biochemistry
• Neurotoxicology
• Environmental Health

Background:

• Cholinesterases, including plasma butyrylcholinesterase (ButChE) and brain acetylcholinesterase (AChE), are crucial enzymes in the nervous system.
• Methylmercury hydroxide (MMH) is a known neurotoxin with potential effects on enzymatic activity.

Purpose of the Study:

• To investigate the interaction between methylmercury hydroxide (MMH) and cholinesterases (ButChE and AChE) in male and female rats.
• To elucidate the mechanism by which MMH affects cholinesterase activity.

Main Methods:

• Subcutaneous administration of MMH to male and female rats at specified doses.
• Measurement of plasma ButChE and brain AChE levels.
• Time-course analysis of enzyme activity and mercury levels in blood and brain tissue.
• Enzymatic kinetic studies (Km and Vmax) and in vitro incubation experiments.

Main Results:

• A single dose of MMH (10 mg/kg) significantly reduced ButChE levels (68% in females, 47% in males) while brain AChE remained largely unaffected.
• ButChE levels decreased when blood mercury reached 22 µg/ml; a 10% AChE reduction occurred at 72 hours with lower brain mercury concentrations (2.0 µg/g).
• MMH treatment reduced the Vmax of ButChE but not Km, and in vitro studies showed MMH is not a direct inhibitor, suggesting indirect interaction.

Conclusions:

• MMH primarily affects ButChE activity in rats, with greater impact observed in females.
• The mechanism involves MMH binding to sulfhydryl groups on the inactive monomeric form of ButChE, preventing the formation of the active enzyme.
• Similar mechanisms are postulated for MMH's effect on AChE, despite less pronounced changes observed in this study.