Antioxidants Found Within the Human Body

The structures of the human body are exposed continuously to a variety of ROS. Humans have evolved an effective antioxidant system to defend against these damaging agents. Different sites of the body contain different antioxidants or contain the same antioxidants but in different amounts. Differences are likely to reflect the different requirements and characteristics of these sites.

Human plasma and other biological fluids are generally rich in scavenging and chain-breaking antioxidants, including vitamin C (ascorbic acid) and 'vitamin E.' Vitamin E is the name given to a group of eight lipid-soluble tocopherols and toco-trienols. In the human diet, 7-tocopherol is the main form of vitamin E, but the predominant form in human plasma is a-tocopherol. Bilirubin, uric acid, glutathione, flavonoids, and carotenoids also have antioxidant activity and are found in cells and/or plasma. Scavenging and chain-breaking anti-oxidants found in vivo are derived overall from both endogenous and exogenous sources. Cells contain, in addition, antioxidant enzymes, the SODs, glutathione peroxidase, and catalase. The transition ros

DNA breakage and mutation

Oncogene activation

Tumor-suppressor gene inactivation

Peroxidation of unsaturated fatty acids

Loss of membrane fluidity/function

OxLDL formation

Enzyme activation/inactivation

Protein crosslinking

Protein fragmentation

Changes in immunogenicity

Carbohydrate crosslinking

Receptor disturbance

Mitochondrial damage/disruption Disordered cellular metabolism Carcinogenesis Atherogenesis Autoimmunity Cell damage/death

Lipoprotein Mitochrodria Ros
Figure 3 Possible involvement of reactive oxygen species (ROS) in ageing and chronic degenerative disease. OxLDL, oxidized low density lipoprotein.

metals iron and copper, which can degrade preexisting peroxides and form highly reactive ROS, are kept out of the peroxidation equation by being tightly bound to, or incorporated within, specific proteins such as transferrin and ferritin (for iron) and caeruloplasmin (for copper). These proteins are regarded as preventive antioxidants. Caeruloplasmin ferroxidase activity is also important for

Somatic cells e.g., Lung

Initiation of change Linked to oxidative- Promotion of growth Uncontrolled at DNA level stress-induced mutation of altered cells growth/local invasion

Malignant tumor formation

Seeding of malignant cells to other organs (metastasis)

Normal Fatty streak Atheroma Occlusion -> myocardial formation linked to oxidation infarction or stroke of low-density lipoprotein

Coronary or carotid artery

Lens of the eye

Lens of the eye

Cataract -» loss of vision

Lens opacities linked to oxidation of crystallin proteins of lens

Cataract -» loss of vision

Figure 4 Antioxidants may help prevent the long-term oxidative changes to DNA, lipid, and protein that lead to age-related disease.

Table 2 Types of antioxidants

Physical barriers prevent ROS generation or ROS access to important biological sites; e.g., UV filters, cell membranes Chemical traps or sinks 'absorb' energy and electrons and quench ROS; e.g., carotenoids, anthocyanidins Catalytic systems neutralize or divert ROS, e.g., the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase

Binding and redox inactivation of metal ions prevent generation of ROS by inhibiting the Haber-Weiss reaction; e.g., ferritin, caeruloplasmin, catechins Sacrificial and chain-breaking antioxidants scavenge and destroy ROS; e.g., ascorbic acid (vitamin C), tocopherols (vitamin E), uric acid, glutathione, flavonoids

ROS, reactive oxygen species.

the non-ROS-producing route of ferrous (Fe(ii)) to ferric (Fe(iii)) oxidation and for incorporating released iron into ferritin for 'safe' iron storage. Haptoglobin (which binds released hemoglobin), hemopexin (which binds released hem), and albumin (which binds transition-metal ions and localizes or absorbs their oxidative effects) can also be regarded as antioxidants in that they protect against metal-ion-catalyzed redox reactions that may produce ROS. An overview of the major types of antioxidants within the body and their interactions is given in Table 2 and Figure 5.

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