Superoxide Dismutase

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Superoxide is a highly reative free radical species, which can cause very profound damage to cells. Superoxide is the anion O2−.[1] with one unpaired and therefore reactive electron. Superoxide is a very toxic substance. It's toxicity is in fact used beneficially by the immune system to destroy invading microorganisms. Phagocytes (white blood cells) engulf invading organisms, such as bacteria and use superoxide to oxidise them. The superoxide is produced in these immune cells by the enzyme NADPH oxidase. A deficiency of this enzyme results in the immunodeficiency syndrome known as chronic granulomatous disease, a syndrome characterised by extreme susceptibility to infection.

Superoxide is also produced in the mitochondria of the cells as a bi-product of the process of aerobic respiration. Mitochondria are the centres for respiration and are often referred to as the powerhouses of the cells, without which a cell cannot function.  In mitochondria the superoxide is produced notably by complex I and complex III.  This free radical is also produced by several other enzymes, an example of which is xanthine oxidase (involved in the formation of uric acid).

Mechanism of action

The toxic affects of superoxide result from its ability to inactivate iron-sulphur containing enzymes.  These enzymes are essential in a large number of metabolic reactions.  Once these enzymes are deactivated, iron is free to undergo a process known as fenton chemistry (see below):

Fe2+ + H2O2 Fe3+ + OH. + OH-

This results in the generation of the highly reactive free radical known as Hydroxyl. 

In its HO2 form, Superoxide also initiates the peroxidation of polyunsaturated fatty acids and when superoxide reacts with carbonyl compounds and halogenated carbons it can create toxic peroxy radicals.

Definition of Superoxide Dismutase

One of the most important free radical scavengers in the human body is the enzyme superoxide dismutase (SOD). This enzyme catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide. Its function is to defend the cells of the body against molecular damage from oxygen. Nearly all cells and cellular organisms use SOD to eliminate superoxide. One of the exceptions is Lactobacillus plantarum and related lactobacilli. These bacteria use a different mechanism for eliminating superoxide.

Structure of Superoxide Dismutase

Structure of Superoxide Dismutase

The role of Superoxide dismutase in the cells

SOD is located in two places with the cells.  The Mitochondria and the cytoplasm.  The SOD that resides in the mitochondria contains manganese and has the formula MnSod.  Mitochondrial SOD is transcribed in the nucleus, but has a targeting sequence that localises it to the matrix of the mitochondria.  The cytoplasmic SOD contains copper and zinc with the formula CuZnSod.  SOD is coded for in genes located on chromosomes 4, 6 and 24.

When cellular superoxide dismutase comes into contact with superoxide, the SOD a reaction takes place, which results in the production of hydrogen peroxide.  For each two superoxides that are encountered by the SOD, one hydrogen peroxide (H2O2) is created.  Hydrogen peroxide does however pose a great danger to the cell as it transforms easily into the highly reactive hydroxyl radical.  A process involving the Fenton chemistry (described previously).  Luckily, there does exist an efficient mechanism for dealing with the hydrogen peroxide.  The enzyme Catalase is produced by the rough endoplasmic reticulum and is concentrated in peroxisomes surrounding the mitochondria (as well as being present in lower concentrations throughout the cell).  The catalase reacts with the hydrogen peroxide to produce water and oxygen.  

There is also another mechanism for neutralising the hydrogen peroxide and thus preventing it from forming hydroxyl radicals.   The selenium containing enzyme Glutathione peroxidise reduces H2O2 by transferring the energy of the reactive peroxides to a small protein called glutathione (a protein containing sulphur). The selenium contained in this enzyme is where a key reaction takes place.  A reaction that transfers electrons from the peroxide to the glutathione.

Reaction

A typical reaction of an SOD protein containing copper (and zinc) looks like this:

Cu2+-SOD + O2- → Cu1+-SOD + O2

Cu1+-SOD + O2- + 2H+ → Cu2+-SOD + H2O2.

In this reaction the oxidation state of the copper changes between +1 and +2.

Mark S D'Arcy

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