Wednesday, April 26, 2006

Antioxidants

In biological systems, the normal processes of oxidation (plus contributions from ionizing radiation and pro-oxidant chemicals) produce highly reactive free radicals. These can readily react with and damage other molecules, including DNA in cell nuclei or mitochondria. In some cases, the body uses free radicals to destroy foreign or unwanted objects, such as in an infection or cancer. However, in the wrong place, the body's own cells may become damaged. Should the damage occur to DNA, the result could increase the possibility of cancer. Antioxidants decrease the damage done to cells by reducing oxidants before they can damage the cell. Antioxidants may be further classified by the products they form on oxidation (these can be antioxidants themselves, inert, or pro-oxidant), by what happens to the oxidation products (the antioxidant may be regenerated by different antioxidants or, in the case of "sacrificial" antioxidants, its oxidised form may be broken down by the organism) and how effective the antioxidant is against specific free radicals.

Free radical damage in the mitochondria of living cells is a byproduct of oxidative phosphorylation. Superoxide radicals are generated, which can damage mitochodria and mitochondrial membranes. Unlike DNA in the cell nucleus, mitochondrial DNA has only a few DNA-repair enzymes and the DNA is not protected by histones.
Many antioxidants, however (including vitamin C and vitamin E) can't get into mitochondria for various reasons (e.g. because they are too hydrophilic to cross mitochondrial membranes or too hydrophobic to cross the cytoplasm). Melatonin is an important natural antioxidant that has been demonstrated to strongly protect mitochondria from damage . A group of scientists in Russia (led by V. Skulachev) have created a custom antioxidant (a Skulachev ion forms the point of the molecule and penetrates the mitochondrial membrane; the antioxidising part is attached behind it) that can enter the mitochondria and stays there due to the membrane potential gradient; preventing damage to DNA.

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