Oxygen-defense mechanisms

Molecular oxygen may take up a single electron from reduced ferrous iron, or from the highly reduced redox components present inside cells. The superoxide anion that is formed is an extremely reactive radical that may either reduce molecules by donating its electron or oxidize them by accepting a second electron forming hydrogen peroxide. When these reactions take place between two superoxide radicals, a spontaneous dismutation follows leading to formation of molecular oxygen and hydrogen peroxide.

+ + ----->+

Superoxide anions may also react with hydrogen peroxide to form the extremely reactive hydroxyl radicals, while hydrogen peroxide by itself may also cause severe damage to the cell. It is thus important to reduce the damage caused by these species of activated oxygen to a minimum. Obligatory and facultative aerobes therefore all have a number of mechanisms at their disposal that protect them against oxidative stress. These are superoxide dismutase, catalase, peroxidase and glutathione. Together these systems prevent membrane damage and damage to their DNA.

• Superoxide dismutase (SOD) is the first defense against the toxic intermediates of oxygen. It significantly accelerates the spontaneous supeoxide dismutation reaction mentioned above:
  + + ----->+
  The turn-over of superoxide dismutase is among one of the highest known for an enzyme (10exp6 / s). Although the half-life of the superoxide anion in water is extremely short, the presence of SOD inside cells reduces this half-life by a thousand fold.
  
• Catalase is the second defense against the toxic intermediates of oxygen. It catalyzes the inactivation of peroxide by the following reaction:
  
  + -----> + 2
  Its major function inside cells is that of a peroxidase (see below)
  
• Peroxidases are the third defense against the toxic intermediates of oxygen. They catalyze the following type of reaction:
  + ROOH -----> + 2 ROH +A
  
• Glutatione (GSH or gamma-glutamyl cysteyl glycine) is another important protectant against oxydant stress. It readily reacts non-enzymatically with peroxides according to the following reaction:
  
  ROOH + 2GSH -----> ROH + GSSG +
  A similar reaction can also be catalyzed by the enzyme glutathione peroxidase.
  
  Oxidized glutathione (GSSG) is then enzymatically reduced by the enzyme gluthathione reductase:
  GSSG + NADPH + -----> 2GSH + NADP+
  The reducing equivalents required to maintain glutathione in the reduced form come from the pentose-phosphate shunt where the enzymes glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase produce NADPH. Red blood cells that are loaded with oxygen-carrying heam and thus are exposed to high concentration of oxygen have an important pentose-phosphate shunt and high activities of catalase and superoxide dismutase.

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