Antioxidants in Food, Vitamins and Supplements

Prevention and Treatment of Disease

Amitava Dasgupta, Kimberly Klein

• Publisher: Elsevier
• Year: 2014
• Print ISBN: 9780124058729
• eBook ISBN: 9780124059177
• Topic: Technology & Engineering
• Subtopic: Nutrition, Dietics & Bariatrics
• Index: Technology & Engineering

Antioxidants in Food, Vitamins and Supplements bridges the gap between books aimed at consumers and technical volumes written for investigators in antioxidant research. It explores the role of oxidative stress in the pathophysiology of various diseases as well as antioxidant foods, vitamins, and all antioxidant supplements, including herbal supplements. It offers healthcare professionals a rich resource of key clinical information and basic scientific explanations relevant to the development and prevention of specific diseases. The book is written at an intermediate level, and can be easily understood by readers with a college level chemistry and biology background.- Covers both oxidative stress-induced diseases as well as antioxidant-rich foods (not the chemistry of antioxidants)- Contains easy-to-read tables and figures for quick reference information on antioxidant foods and vitamins- Includes a glycemic index and a table of ORAC values of various fruits and vegetables for clinicians to easily make recommendations to patients

Chapter 1

Introduction to Free Radicals and the Body’s Antioxidant Defense

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

Contents

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.

Box 1.1

Common Free Radicals and Oxidants Encountered in Human Physiology

Free Radicals

Superoxide anion radical

Hydroxyl radical

Hydroperoxyl radical

Peroxyl radical

Lipid radical

Lipid peroxyl radical

Lipid alkoxyl radical

Nitric oxide

Nitrosyl cation

Thiyl radical

Protein radical

Oxidants

Singlet oxygen

Ozone

Hydrogen peroxide

Hypochlorite

Nitrous acid

Peroxynitrous acid

Nitrous oxide

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.

1.2.1 Various Sources of Free Radicals

There are two sources of free radicals: endogenous sources and exogenous sources. Major endogenous sources of free radicals are summarized in Table 1.1. The most common reactive oxygen species are superoxide anion, hydrogen peroxide, hydroxyl radicals, peroxyl radicals, singlet oxygen, and ozone. The production of superoxide occurs mostly within mitochondria. The mitochondrial electron transport chain is the main source of energy that is stored in adenosine triphosphate (ATP) molecules. Movement of electrons from oxidizable organic molecules to molecular oxygen is responsible for ATP production by the mitochondrial electron transport system. During this process, superoxide anions are generated due to leaking of electrons to oxygen. Superoxide is also formed enzymatically in the process of reduction of molecular oxygen mediated by nicotinamide adenine dinucleotide phosphate oxidase (NADPH oxidase) and xanthine oxidase in mitochondria. Superoxide has a relatively longer half-life than that of other free radicals, but it is less reactive than the hydroxyl radical. Inflammatory cells also produce relatively large amounts of superoxide. Superoxide is membrane impermeable but can diffuse within cells [5].

Table 1.1

Endogenous Sources of Free Radicals

Physiological Process	Comment
Mitochondrial respiration	Essential process of life that generates superoxide anion radical.
Autoxidation	Autoxidation of many biological molecules (hemoglobin, myoglobin, catecholamines, etc.) in the human body can produce free radicals. Superoxide is the primary free radical formed.
Enzymatic reaction	Many enzymatic reactions involving xanthine oxidase, lipoxygenase, aldehyde oxidase, etc. can generate free radicals.
Respiratory burst	This is a process in which phagocytes consume a large amount of oxygen during phagocytosis.
Metal ions	Metal ions such as copper ion and ferrous ion, which are essential for the body, can react with hydrogen peroxide to produce free radicals.
Strenuous exercise	May activate xanthine oxidase, producing free radicals.
Infection	May produce free radicals because the immune system may try to neutralize invading microorganisms with a burst of free radicals.
Ischemia/reperfusion	May activate xanthine oxidase, causing free radical generation.

Peroxisomes are another significant source for free radicals. Peroxisomes are specialized cytoplasmic organelles that carry out important physiological functions such as β-oxidation of long-chain and very-long-chain fatty acids and degradation of uric acid. Peroxisomal oxidase is capable of generating hydrogen peroxide. The reaction of xanthine and xanthine oxidase produces the superoxide anion and hydrogen peroxide through one-electron and two-electron reduction of molecular oxygen, respectively, to form uric acid. Hydrogen peroxide is a relatively stable agent that is permeable to cell membranes. Hydrogen peroxide can generate free radicals such as the hydroxyl radical but cannot directly oxidize lipid or DNA. Therefore, cytotoxicity of hydrogen peroxide is due to its ability to produce hydroxyl radicals through metal-catalyzed reactions such as the Fenton reaction. However, hydroxyl radicals are highly reactive and can damage any biomolecules close to their site of generation. These radicals are some of the most dangerous free radicals encountered in physiology [6]. Singlet oxygen is an electronically excited form of oxygen, but it is not a free radical. However, singlet oxygen is a reactive oxygen species generated during dismutation of superoxide anion in water.

Another endogenously produced oxygen free radical is the peroxyl radical (ROO^•), the simplest form of which is HOO^•, which is the protonated form of superoxide. Hydroperoxy radical is known to initiate lipid peroxidation. As mentioned previously, nitric oxide (NO^•) is synthesized from L-arginine through nitric oxide synthases (NOS) in many cell types. Nitric oxide is a water-soluble, short-lived free radical that plays an important role as a signaling molecule in the body. Mammalian cells contain three genes encoding NOS (NOS1, NOS2, and NOS3), with 51–57% homology between isomers. NOS1, also known as nNOS (isoform first purified from neuronal tissue), and NOS3, also known as eNOS (isoform first found in endothelial cells), are also termed constitutive because they are expressed cont...

Table of contents

• Cover image
• Title page
• Table of Contents
• Copyright
• Preface
• Chapter 1. Introduction to Free Radicals and the Body’s Antioxidant Defense
• Chapter 2. Methods for Measuring Oxidative Stress in the Laboratory
• Chapter 3. Oxidative Stress Induced by Air Pollution and Exposure to Sunlight
• Chapter 4. Oxidative Stress Caused by Cigarette Smoking, Alcohol Abuse, and Drug Abuse
• Chapter 5. Oxidative Stress Induced by Household Chemicals
• Chapter 6. Psychological Stress-Induced Oxidative Stress: Differences Between Personality Types, Gender, and Race
• Chapter 7. Oxidative Stress and Cardiovascular Diseases
• Chapter 8. Oxidative Stress and Cancer
• Chapter 9. Diabetes and Oxidative Stress
• Chapter 10. Role of Oxidative Stress in Neurodegenerative Diseases and Other Diseases Related to Aging
• Chapter 11. Oxidative Stress Related to Other Diseases
• Chapter 12. Fruits, Vegetables, and Nuts: Good Sources of Antioxidants
• Chapter 13. Tea, Coffee, and Chocolate: Rich Sources of Antioxidants
• Chapter 14. Alcoholic Beverages: Antioxidant and Other Health Benefits of Moderate Consumption
• Chapter 15. Antioxidant Vitamins and Minerals
• Chapter 16. Herbal and Other Dietary Supplements That Are Antioxidants
• Chapter 17. Combating Oxidative Stress with a Healthy Lifestyle
• Index