Mechanism of oxidation of oxymyoglobin by copper ions: comparison of sperm whale, horse, and pig myoglobins.

This study explored how copper ions interact with and oxidize different types of oxymyoglobin, a form of the protein myoglobin found in mammals like sperm whales, horses, and pigs.

Research Overview

• The researchers investigated how factors such as the concentration of copper ions (Cu2+), the pH and ionic strength of the solution, and the presence of redox-inactive zinc ions impact the rate of oxidation of myoglobin in sperm whales, horses, and pigs.
• They noted that while these three types of myoglobin have very similar spatial structures and the same redox potentials, they differ in the number of histidines, a type of amino acid, on their surfaces.

Oxidation Pathways

• The study found that oxidation of oxymyoglobin can occur through two distinct pathways in the presence of copper ions. The relevant pathway depends on which histidine molecule binds onto the copper ions, and the stability of the resulting molecular complex.
• A slower, pH-dependent pathway is observed when the concentration of copper ions and the myoglobin are the same. This process is characterized by the strong binding of copper ions to His113 and His116 histidines, and is relevant to sperm whale and horse myoglobins. Notably, a similar process does not occur in pig myoglobin, as it doesn’t contain an analogue to the His residue.

Observations and Conclusion

• Under the same conditions, a rapid, non-catalytic oxidation process is seen in pig myoglobin. The researchers proposed that this fast oxidation is due to the copper ions forming a complex with a histidine (His97) near the myoglobin’s heme group. However, because this phase isn’t observed in sperm whale and horse myoglobins, it’s thought that the affinity of His97 for copper ions is significantly less than that of the other histidine residues.
• It was found that increasing the concentration of copper ions does not proportionately increase the oxidation rate of the sperm whale and horse myoglobins.
• Finally, the researchers discussed the implications of their findings, focusing on which Cu2+ binding sites of myoglobin contribute most to the histidine reaction rate at variable ratios of copper ions to myoglobin, ranging from 0.25 to 10.