Oxygen Radicals

Oxygen Can Be Dangerous!

Our bodies, of course, constantly require oxygen. The reason is that we need somewhere to place the used electrons that drive our energy requiring processes. These electrons are derived from molecules such as fats and carbohydrates and are transferred around the cells by molecules such as the coenzymes NADH and NADPH. When the electrons have given up their energy, they are combined with oxygen to form water. Since the electrons are given to water, we say that the oxygen is reduced, forming water in the process. This is going on constantly in the body, and we end up with a completely harmless substance, water.

But observe that two electrons are required for each oxygen atom to form H2O. What happens if only one electron is given to each oxygen atom? Instead of water, we wind up with a radical. (What is the definition of a radical? Be sure to use "orbital" in your answer.) Oxygen radicals tend to be quite reactive, and can damage many of the most important macromolecules in the body. Fortunately, only tiny amounts are made in the normal course of metabolism.

Oxygen Radicals and Phagocytosis

However, in phagocytosis oxygen radicals can be useful. Consider a neutrophil that has just engulfed a bacterium. This is fine, but now the neutrophil has to deal somehow with the living, dangerous microorganism it has just surrounded. To this end, lysosomes fuse with the phagosome, forming a phagolysosome. Proteases are introduced into the phagosome in this way. But, in addition, a membrane protein called phagocyte oxidase(NADPH oxidase) winds up in the membrane of the phagolysosome.

Phagocyte oxidase is an enzyme that takes an electron from NADPH and transfers its to O2, forming the superoxide radical, O2-. . (The black dot indicates a radical.) The superoxide radical is only moderately reactive. However, it is soon converted to hydrogen peroxide by the enzyme superoxide dismutase. Hydrogen peroxide can damage microbes, but can be converted to something far more effective.

A further enzyme found in the phagolysosome of a neutrophil is myeloperoxidase. This converts hydrogen peroxide to hypochlorite (HOCl). This is bleach! It readily kills almost any microorganism.

A second possible fate of the hydrogen peroxide is not helpful, but damaging to the body. If Fe++ or another heavy metal is present, the hydrogen peroxide is readily converted to the hydroxyl radical, OH.. (Please note this is completely different that the hydroxyl ion.) The hydroxyl radical is very reactive and damages most macromolecules, including DNA, proteins and lipids.

Thus, it is very important that iron never be free in the body. But iron is an important constituent of the body. For example, it is part of hemoglobin. To protect the body, iron is always tightly bound. It moves through the blood bound to the protein transferrin and is stored in cells bound to the protein ferritin.

Cells throughout the body clearly need protection from the molecules described above. Most of these cells have superoxide dismutase and another enzyme, catalase (or another enzyme, glutathione peroxidase), which converts the hydrogen peroxide to oxygen and water. In other words, the combination of superoxide dismutase and catalase removes oxygen radicals and thus is protective for cells in the body.

Nitric Oxide

Nitric oxide is also a radical and is highly reactive. In the body, it last only a few seconds. Nitric oxide is made from the amino acid arginine by nitric oxide synthase. There are three forms of this enzyme: neuronal, endothelial, inducible. The neuronal form makes nitric oxide that serves as a signalling molecule between neurons. The endothelial form is in blood vessels and produces nitric oxide that causes their dilation. The inducible form is found in macrophages and certain other immunological cells, and it is this form that plays a role in phagocytosis.

The nitric oxide produced by macrophages is used to attack microbes. The molecule is toxic to bacteria. Furthermore, it reacts with superoxide to make further toxic molecules. In certain pathological situations, nitric oxide can be produced in quantities that cause serious damage to the body. For example, this can occur with interruption of blood flow during shock.

Quick Quiz

Fill in Answer Correct False Correct Answer
How many electrons can fit in one orbital?
What enzyme forms the superoxide radical?
What enzyme causes hypochlorite to form?
Name a coenzyme that transfers electrons around the body.

(Spelling must be correct)
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