We can’t live without oxygen. Our cells rely on oxygen as the final acceptor of electrons in respiration, allowing us to extract far more energy from food than would be possible without oxygen. But oxygen is also a dangerous compound. Reactive forms of oxygen, such as superoxide (oxygen with an extra electron), leak from the respiratory enzymes and wreak havoc on the cell. This superoxide can then cause mutations in DNA or attack enzymes that make amino acids and other essential molecules. This is a significant problem: one study showed that for every 10,000 electrons transferred down the respiratory pathway in Escherichia coli cells, about 3 electrons end up on superoxide instead of the proper place. To combat this potential danger, most cells make superoxide dismutase (SOD), an enzyme that detoxifies superoxide.
The Science in Dismutation
As you might guess from its name, SOD dismutes superoxide. Dismutation is a term that refers to a special type of reaction, where two equal but opposite reactions occur on two separate molecules. SOD takes two molecules of superoxide, strips the extra electron off of one, and places it on the other. So, one ends up with an electron less, forming normal oxygen, and the other ends up with an extra electron. The one with the extra electron then rapidly picks up two hydrogen ions to form hydrogen peroxide. Of course, hydrogen peroxide is also a dangerous compound, so the cell must use the enzyme.
Superoxide dismutase (SOD) catalyzes the destruction of the O2- free radical. Superoxide: superoxide oxidoreductase – Enzymatic Reaction
Exploring the Structure
Cu/Zn superoxide dismutase is a very efficient enzyme. Researchers have determined that one out of every ten collisions between superoxide and the enzyme will lead to a reaction. This is far more than expected, since the active site covers only a small portion of the enzyme surface, and we might expect that most collisions would occur somewhere else on the surface. The shape and characteristics of the active site, however, may give some hints to this efficiency. The active site is funnel shaped, with the copper and zinc (colored green here) at the base of the funnel. The strong positive charge of the metal ions, along with two nearby positively-charged amino acids (colored blue here), serve to draw the negatively-charged superoxide (red) into the funnel.
Structure of Structure Cu/Zn superoxide dismutase
Superoxides and Superoxide Dismutase: Physiology, Biochemistry, and Inorganic Mechanism
SOD has recently gained notoriety for its connection with amyotrophic lateral sclerosis, more commonly known as Lou Gehrig’s disease. Recent research has shown that one of the mutations is found in the gene for SOD. Scientists are now studying the role of SOD in the disease, hoping that this knowledge will lead to new treatments and cures.
The list of pathophysiological conditions that are associated with the overproduction of superoxide anions expands every day. The most exciting realization is that there seems to be a similarity between the tissue injury that is observed in various disease states, as superoxide anions produce tissue injury and associated inflammation in all tissues in similar ways. Tissue injury and inflammation form the basis of many disease pathologies, including ischaemia and reperfusion injuries, radiation injury, hyperoxic lung damage and atherosclerosis. This commonality provides a unique opportunity to manipulate numerous disease states with an agent that removes superoxide anions.
Superoxide anions produce tissue injury and associated inflammation
Mitochondrial Theory of Aging