Oxygen-dependent conformation change of hemoglobin modulates methylmercury binding

Area of Science:

• Environmental Toxicology
• Biochemistry
• Aquatic Biology

Background:

• Methylmercury bioaccumulation in fish is a significant human health concern, primarily through seafood consumption.
• While environmental intake is studied, methylmercury transport within fish, particularly its binding to hemoglobin, remains less understood.
• Hemoglobin's oxygen-carrying function influences its structure, yet its interaction with methylmercury under varying oxygen conditions is largely unexplored.

Purpose of the Study:

• To investigate the influence of oxygen levels (normoxia vs. hypoxia) on methylmercury binding to fish hemoglobin.
• To elucidate the molecular mechanisms underlying methylmercury-hemoglobin interactions under different oxygenation states.
• To provide a comprehensive understanding of methylmercury transport and distribution within fish.

Main Methods:

• Utilized fluorescence spectroscopy, isothermal titration calorimetry, and circular dichroism spectroscopy.
• Employed PyMOL visualization system for structural analysis and molecular docking simulations.
• Quantified methylmercury binding capacity under both normoxic and hypoxic conditions.

Main Results:

• Significantly less methylmercury bound to hemoglobin under hypoxic conditions compared to normoxic conditions.
• Methylmercury binding to hemoglobin was more spontaneous under normoxic conditions than under hypoxic conditions.
• Conformational changes in hemoglobin, influenced by oxygen levels, were observed to affect methylmercury binding capacity.

Conclusions:

• Oxygen content critically modulates methylmercury binding to hemoglobin in fish.
• Reduced oxygen availability decreases methylmercury's binding affinity to hemoglobin, potentially altering its bioaccumulation.
• These findings offer a novel perspective on methylmercury dynamics in aquatic environments and its toxicological implications.