Free radicals are generated during normal cellular function and are part of the natural physiological process of all living beings. Free radicals also play important physiological roles, including signal transduction and gene expression, but the majority of free radicals generated must be neutralized by the body’s antioxidant defense for optimal health. The body has many antioxidants that are classified under two broad categories: water-soluble and fat-soluble. Water-soluble antioxidants, such as vitamin C, glutathione, lipoic acid, and uric acid, are major antioxidants present in human blood. Fat-soluble antioxidants, such as carotenes, vitamin E, and coenzyme Q10, can be found in both blood and cells. In addition, several enzymes also act as antioxidants, most notably superoxide dismutase, catalase, and peroxidases.

Keywords

Reactive oxygen species; superoxide anion; nitric oxide; antioxidant enzymes

1.1 Introduction

1.2 Free Radicals

1.2.1 Various Sources of Free Radicals

1.2.2 Damage of Biomolecules by Free Radicals

1.2.3 Physiological Role of Free Radicals

1.3 The Body’s Antioxidant Defense

1.3.1 Enzymes as Antioxidants

1.3.2 Chain-Breaking Antioxidants

1.3.3 Exercise and Antioxidant Status of Blood

1.3.4 Markers for Oxidative Stress in Human Blood

1.4 Conclusion

References

1.1 Introduction

The “oxygen paradox” is defined by the fact that aerobic organisms require oxygen for survival but oxygen is also inherently toxic to these organisms due to its association with free radical generation and oxidative stress. Various free radicals are common products of respiration and other biochemical reactions in cells that are normal physiological processes essential for survival. To survive in an unfriendly oxygen environment, living organisms generate water- and lipid-soluble antioxidants that can neutralize these highly reactive free radicals [1]. For healthy living, a delicate balance must be maintained between oxidative stress and antioxidant defense of the body. If the body’s antioxidant mechanism does not operate optimally, excess free radicals can damage various biomolecules, including lipids, proteins, carbohydrates, and nucleic acids.

1.2 Free Radicals

A free radical is defined as an atom or molecule containing one or more unpaired electrons that are capable of free existence. Free radicals can be generated as products of homolytic, heterolytic, or redox reaction, and they usually consist of reactive oxygen species or reactive nitrogen species. Reactive oxygen species include oxygen-carrying free radicals as well as other reactive oxygen species such as hydrogen peroxide, which is not a free radical. Similarly, reactive nitrogen species include both nitrogen-containing free radicals and other reactive molecules in which the reactivity center is nitrogen [2]. Common free radicals and oxidants are summarized in Box 1.1.

Free radicals are generated during normal respiration and cellular functions. Under normal physiological conditions, approximately 2% of oxygen consumed by the human body during respiration is converted into superoxide anion free radical, which is negatively charged (O2•−) [3]. The human body also contains approximately 4.5 mg of iron, most of which is found in hemoglobin and other proteins. However, a small amount of iron that is found forming complexes with a variety of small molecules can react with hydrogen peroxide, producing the hydroxyl radical (Fenton reaction). In general, oxygen-centered free radicals (reactive oxygen species), such as superoxide, the hydroxyl radical, peroxyl radical, and alkoxy radical, and nitrogen oxide, play an important role in inducing oxidative stress [4].

Nitric oxide (NO•) is synthesized from L-arginine by many cell types through nitric oxide synthesis. Nitric oxide and superoxide are the major reactive species produced in cells. Both superoxide and nitric oxide can react with other species, producing reactive oxygen species and reactive nitrogen species, respectively. Nitric oxide can also bind to transition metals such as ferrous ions, and it plays an important role in the formation of cyclic guanosine monophosphate, a second messenger [5]. In general, superoxide anion radicals and nitric oxide are primary free radicals generated by cells during normal physiological functions.