Manganese Superoxide Dismutase (MnSOD)

The enzyme, its reaction and mechanism:

MnSOD catalyzes the dismutation of two molecules of superoxide anion into water and hydrogen peroxide:

2O₂-^. + 2H⁺ Þ O₂ + H₂O₂

The catalytic mechanism is shown below illustrating the oxidation of the Mn+3 enzyme to Mn+2 with one superoxide anion and the reduction of the enzyme back to the ground state Mn+3. Also shown is the entry of the human enzyme into an “inactive form” which we have designated the product inhibited form of the enzyme.

The Structure:

Human MnSOD is a tetrameric enzyme with four identical subunits each harboring a Mn+3 atom. The active site of the enzyme is also depicted below illustrating some of the active site residues.

The Physiological Relevance:

This anti-oxidant enzyme functions primarily to protect mitochondrial components from superoxide liberated as a normal byproduct of respiration. Complex I and Complex III release superoxide radical as a consequence of normal respiration, with estimates of 1-5% of the oxygen consumed being liberated as superoxide anion. MnSOD is therefore the cells primary defense against free radical mediated damage. In addition, stimulated levels of the enzyme have evolved to address increased free radical production during an inflammatory episode.

Mitochondrial Electron Transport: