antioxidant biochemistry
antioxidant biochemistry
antioxidant biochemistry

 



Oxidation, Free Radicals and Antioxidants

This article goes into some detail in explaining the life sustaining bio-chemical oxidation processes, the free radicals involved and the resultant need for antioxidants. Free radicals are “highly reactive molecules with an unsatisfied electron valence pair. Free radicals are produced in both normal and pathological1 processes. They are proven or suspected agents of tissue damage in a wide variety of circumstances including radiation, damage from environment chemicals, and aging. Natural and pharmacological prevention of free radical damage is being actively investigated”.2

Atoms and Molecules | Oxidation | Free Radicals | Chain Reaction | Multiple Effects | Antioxidants

Atoms and Molecules

Atoms are described as the smallest building blocks of matter.3 Atoms themselves consist of a nucleus, neutrons, protons and electrons. The nucleus is the centre, the other three are positively charged (protons), negatively charged (electrons), or neutral particles. The number of protons in the atom’s nucleus determines the number of electrons surrounding it. They should always be the same.4

It is the electrons that are involved in chemical reactions and are the substance that bonds atoms together to form molecules. Therefore a molecule simply means two or more atoms bonded by means of shared electrons.

Enjoy Life atom free radical
Electrons surround, or "orbit" the nucleus in one or more "shells". The innermost shell is full when it has two electrons. When the first shell is full, electrons begin to fill the second shell, and so on.

The most important structural feature of an atom for determining its chemical behaviour is the number of electrons in its outer shell. A substance that has Enjoy Life molecule free radicala full outer shell tends to be at its most stable, and therefore tends not to enter in chemical reactions (this is also referred to as an inert substance). As a rule atoms actively seek to reach this state of maximum stability, and therefore an atom will try to balance its outer shell by:

  • Gaining (which generally means stealing from other atoms) or losing electrons to either completely fill or empty its outer shell (any atom that uses this method is known as a free radical)
  • Sharing its electrons by bonding together with other atoms in order to complete its outer shell

    Atoms often complete their outer shells by sharing electrons with other atoms. By sharing electrons, the atoms are bound together and satisfy the conditions of maximum stability for the molecule.5



    Atoms and Molecules | Oxidation | Free Radicals | Chain Reaction | Multiple Effects | Antioxidants

    Oxidation

    Oxidation and reduction are redox chemical reactions. Most people can understand oxidation damage, as they are familiar with the process of rust formation of iron exposed to oxygen. Probably the most familiar free-radical reaction for most people is combustion (“burning”).6 In order for combustion to occur, the bond between the two oxygen atoms must be broken. This bond can be overcome by heat, requiring high temperatures, or the heat requirement can be lowered by enzymes to initiate reactions at the temperatures inside living things. Breaking such bonds and reforming of others will also create heat (energy).

    Ironically, this energy-generation mechanism, which is so essential to life, can also set the stage for cell damage. The oxidation of foodstuffs (the conversion of food to energy) is like a controlled fire that liberates energy but can also let sparks fly, giving rise to potential damage. The sparks in this analogy are free electrons escaping the body’s “transport” system. These unpaired electrons readily form free radical molecules, which are chemically reactive and highly unstable.7

    The two most important oxygen-centered free radicals are superoxide and hydroxyl radical. They are derived from molecular oxygen under reducing conditions. However, because of their reactivity, these same free radicals can participate in unwanted side reactions resulting in cell damage. Radicals requiring more energy to form are less stable than those requiring less energy.8



    Atoms and Molecules | Oxidation | Free Radicals | Chain Reaction | Multiple Effects | Antioxidants

    Free Radicals

    Normally, the bonds between atoms do not split in a way Enjoy free radical information that leaves a molecule with an odd, unpaired electron. But when weak bonds split, free radicals are formed. Free radicals are very unstable and react quickly with other compounds, trying to capture the needed electron to gain stability. Generally, free radicals attack the nearest stable molecule, "stealing" its electron. When the "attacked" molecule loses its electron, it becomes a free radical itself, beginning a chain reaction. Once the process is started, it can cascade, finally resulting in the disruption of living cells.9

    According to Gerhard Herzberg, who won the Nobel prize for his research of electronic structure and geometry of radicals, the preferred definition of free radicals is: "any transient (chemically unstable) species (atom, molecule, or ion)".10

    The vast majority of free radicals that exist in your body at any given moment can be traced back to one of the following sources:

  • Everyday metabolic pathways that occur in your body to produce energy (oxidation)
  • Environmental toxins, such as industrial pollutants, household chemicals, and cigarette smoke
  • Physical stressors, such as unhealthy oils, food preservatives, and the wide variety of chemicals that are found in almost all highly refined foods
  • Emotional stress11


  • Atoms and Molecules | Oxidation | Free Radicals | Chain Reaction | Multiple Effects | Antioxidants

    Chain Reaction

    Free radicals are atoms or molecules that contain unpaired electrons. Since electrons have a very strong tendency to exist in a paired state (and an atom’s number of electrons must match its number of protons), free radicals can indiscriminately pick up (steal) electrons from other atoms. This in turn converts those other atoms into secondary free radicals, thus setting up a chain reaction that can cause substantial biological damage if uncontrolled.12

    In chemistry, free radicals take a vital part in radical addition and radical substitution as reactive intermediates. Chain reactions involving free radicals can usually be divided into three distinct processes: initiation, propagation, and termination.

  • Initiation reactions are those that result in a net increase in the number of free radicals. They may involve the formation of free radicals from stable species or they may involve reactions of free radicals with stable species to form more free radicals.
  • Propagation reactions are those reactions involving free radicals in which the total number of free radicals remains the same.
  • Termination reactions are those reactions resulting in a net decrease in the number of free radicals. Typically two free radicals combine to form a more stable species, for example: 2Cl forming Cl2 13

    When free radicals steal an electron from a surrounding compound or molecule a new free radical is formed in its place. The newly formed radical then looks to return to its ground state by stealing electrons from cellular structures or molecules. Thus the chain reaction continues and can be "thousand of events long."14

    The next two paragraphs are a little complex, included especially for those who want to know more technical details as they relate to the impact of free radicals on health. If you do not need such detail, skip to Multiple Effects.

    Polyunsaturated fatty acids (PUFAs) are abundant in cellular membranes and in low-density lipoproteins (LDL).15 The PUFAs allow for fluidity of cellular membranes. A free radical prefers to steal electrons from the lipid membrane of a cell, initiating a free radical attack on the cell known as lipid peroxidation. Reactive oxygen species target the carbon-carbon double bond of polyunsaturated fatty acids. The double bond on the carbon weakens the carbon-hydrogen bond allowing for easy dissociation of the hydrogen by a free radical.16

    A free radical will steal the single electron from the hydrogen associated with the carbon at the double bond. In turn this leaves the carbon with an unpaired electron and hence it becomes a free radical. In an effort to stabilize the carbon-centered free radical molecular rearrangement occurs. The newly arranged molecule is called a conjugated diene (CD). The CD then very easily reacts with oxygen to form a peroxy radical. The peroxy radical steals an electron from another lipid molecule in a process called propagation. This process then continues in a chain reaction.17



    Atoms and Molecules | Oxidation | Free Radicals | Chain Reaction | Multiple Effects | Antioxidants

    Multiple Effects

    Damage caused by free radicals is currently believed to contribute to more than 70 disorders. These include:

    • Allergies
    • Alzeimers
    • Arthritis
    • Cancer
    • Cataracts
    • Dental Decay
    • Depression
    • Diabetes
    • Hay Fever
    • Memory Loss
    • Parkinson's
    • Phlebitis
    • P.M.S.
    • Prostatitis
    • Rheumatism
    • R.S.I., O.O.S.E.
    • Senility
    • Skin Disorders
    • Sports Injuries
    • Stress
    • Surgery Recovery
    • Ulcers
    • Varicose Veins
    • Wrinkles

    Cell membranes are made of unsaturated lipids. The unsaturated lipid molecules of cell membranes are particularly susceptible to the damaging free radicals process and readily contribute to the uncontrolled chain reaction. Oxidative damage, another name for the chemical reaction that free radicals cause, can lead to a breakdown or even hardening of lipids, which make up all cell walls.

    If the cell wall is hardened (lipid peroxidation) then it becomes impossible for the cell to properly get its nutrients, or to get signals from other cells to perform an action. Many other cellular activities can also be affected. In addition to the cell walls, other biological molecules are also susceptible to damage, including RNA, DNA and protein enzymes.

    Enjoy Life DNA oxidation informationThe primary site of free radical damage is the DNA found in the mitochondria. Mitochondria are small membrane-enclosed regions of a cell that produce the chemicals a cell uses for energy. Mitochondria are the "energy factories" of the cell.

    Every cell contains an enormous set of molecules called DNA, which provide chemical instructions for a cell to function. This DNA is found in the nucleus of the cell, which serves as the "command center" of the cell, as well as in the mitochondria. The cell automatically fixes much of the damage done to nuclear DNA. However, the DNA in the mitochondria cannot be readily fixed.

    Hence, this free radical generation process can disrupt all levels of cell function. This is why free radical damage is thought to underly so many conditions, including being such a basic mechanism of tissue injury. It damages us at the cellular level.18

    Besides tissue injury, free radical damage is held to be responsible for premature aging. The free-radical theory of aging19 suggests that organisms age prematurely because cells accumulate free radical damage with the passage of time.

    More recently, the relationship between disease and free radicals has led to the formulation of a greater generalization about the relationship between aging and free radicals. In its strong form, the hypothesis states that aging per se is a free radical process. The "weak" hypothesis holds that the degenerative diseases associated with aging generally involve free radical processes and that, cumulatively, these make you age. The latter is generally accepted, but the "strong" hypothesis awaits further proof. Both models trace back to Denham Harman's work.20 Some of the scientific evidence includes:

  • Results have demonstrated that the overexpression21 of catalase, an enzyme involved in the decomposition of hydrogen peroxide, increased both the average lifespan and maximum lifespan of mice by 20%. However, the authors of that paper also indicated that the lifespan extension effect had apparently lessened in new generations of these mice.22
  • Making a well-studied roundworm, Caenorhabditis elegans, more susceptible to free radicals has led to shortened lifespan. However, increasing atmospheric oxygen tension above the normal 21% O2, does not meaningfully decrease lifespan of C. elegans. On the other hand, consistent with the free radical theory, it does shorten lifespan of the fruit fly Drosophila.23
  • Drosophila that have mutations in enzymes relating to ROS metabolism have also been shown to have dramatically reduced life-spans, increased susceptibility to oxidative stress and ionizing radiation, partial female and complete male sterility, and a general “enfeebled” phenotype (characterized by deformed wings and abdomen).24
  • While genetic manipulations that increase the levels of oxidative damage generally do shorten lifespan in mice, there is as yet very limited evidence that decreasing free radicals below their normal levels, actually extends lifespan (see above).
  • Feeding of antioxidants, which should increase lifespan if the theory is correct, can extend average but not maximum lifespan in mice. Even so, this effect is weak when it is observed and overall inconsistent.25

    Free radicals have also been implicated as playing a role in the etiology of cardiovascular disease and cancer.26 Many forms of cancer are thought to be the result of reactions between free radicals and DNA, resulting in mutations that can adversely affect the cell cycle and potentially lead to malignancy.

    Some of the symptoms of aging such as arteriosclerosis are also attributed to free-radical induced oxidation of many of the chemicals making up the body. In addition free radicals contribute to alcohol-induced liver damage, perhaps more than alcohol itself. Radicals in cigarette smoke have been implicated in inactivation of alpha 1-antitrypsin in the lung. This process promotes the development of emphysema.

    Free radicals may also be involved in Parkinson's disease, senile and drug-induced deafness, schizophrenia, and Alzheimer's. The classic free-radical syndrome, the iron-storage disease hemochromatosis, is typically associated with a constellation of free-radical-related symptoms including movement disorder, psychosis, skin pigmentary melanin abnormalities, arthritis, and diabetes mellitus.27

    This free radical damage cannot be prevented or cured by any drugs - in fact most drugs are sources of MORE free radicals in the body.



    Atoms and Molecules | Oxidation | Free Radicals | Chain Reaction | Multiple Effects | Antioxidants

    Antioxidant

    Antioxidant means "against oxidation." Antioxidants work to protect other atoms from the effects of free radical attack, including protecting lipids from peroxidation. Antioxidants are effective because they are willing to give up their own electrons to free radicals. When a free radical gains the electron from an antioxidant it no longer needs to attack the cell and the chain reaction of oxidation is broken.28

    After donating an electron an antioxidant becomes a free radical by definition. However, antioxidants in this state are not harmful because they have the ability to accommodate the change in electrons without becoming reactive.29

    Because free radicals are necessary for life, the body has a number of mechanisms to minimize free radical induced damage and to repair the damage that does occur. These include the enzymes superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase.

    In addition, antioxidants play a key role in these defence mechanisms. Some antioxidants are manufactured within the body and others can also be extracted from the food humans eat such as fruits, vegetables, seeds, nuts, meats, and oil. There are two lines of antioxidant defence within each cell.

    The first line, found in the fat-soluble cellular membrane consists of vitamin E, beta-carotene, and coenzyme Q.30 Of these, vitamin E is considered the most potent chain breaking antioxidant within the membrane of the cell. It is the primary defender against oxidation and lipid peroxidation

    Inside the cell the second line, water soluble antioxidant scavengers, are present. These include vitamin C, glutathione peroxidase, superoxide dismutase (SD), and catalase.31 Vitamin C is the most abundant water-soluble antioxidant in the body. It acts primarily in cellular fluid. It is of particular note in combating free-radical formation caused by pollution and cigarette smoke. Also helps return vitamin E to its active form.32

    Further, there is good evidence bilirubin and uric acid can act as antioxidants to help neutralize certain free radicals. Bilirubin comes from the breakdown of red blood cells' contents, while uric acid is a breakdown product of purines. Too much bilirubin, though, can lead to jaundice, which could eventually damage the central nervous system, while too much uric acid causes gout.33

    So antioxidants neutralize free radicals by donating one of their own electrons, ending the electron-"stealing" reaction. The antioxidant nutrients themselves do not become free radicals after donating an electron because they are stable in either form (‘giving’ away the required number of electrons to become stable). They act as scavengers, helping to prevent cell and tissue damage that could lead to disease.

    Although there are several enzyme systems within the body that scavenge free radicals, the principle micronutrient (vitamin) antioxidants are vitamin E, beta-carotene, and vitamin C. Additionally, selenium, a trace metal that is required for proper function of one of the body's antioxidant enzyme systems, is sometimes included in this category. The body cannot manufacture these micronutrients so they must be supplied in the diet.34

    Vitamin E : d-alpha tocopherol is a fat-soluble vitamin present in nuts, seeds, vegetable and fish oils, whole grains (esp. wheat germ), fortified cereals, and apricots. Current recommended daily allowance (USRDA35) is 15 IU per day for men and 12 IU per day for women.36

    Vitamin C : Ascorbic acid is a water soluble vitamin present in citrus fruits and juices, green peppers, cabbage, spinach, broccoli, kale, cantaloupe, kiwifruit, and strawberries. The RDA is 60 mg per day. Intake above 2000 mg may be associated with adverse side effects in some individuals.37

    Beta-carotene is a precursor to vitamin A (retinol) and is present in liver, egg yolk, milk, butter, spinach, carrots, squash, broccoli, yams, tomato, cantaloupe, peaches, and grains. Because beta-carotene is converted to vitamin A by the body there is no set requirement. Instead the RDA is expressed as retinol equivalents (RE), to clarify the relationship. (NOTE: Vitamin A has no antioxidant properties and can be quite toxic when taken in excess.)38

    Here are some practical notes on how to prevent free radicals from significantly compromising your health39:

  • Avoid hydrogenated oils, fried foods in restaurants, and highly refined foods - all of these foods are typically rich in free radicals.
  • Minimise your charcoal-grilled meats and animal products that have been cooked at high temperatures - these foods are also abundant in free radicals.
  • Eat plenty of fresh vegetables, such as lettuce, celery, bell peppers, carrots, and tomatoes. Grown in optimal conditions, and truly fresh, vegetables and fruits are rich in natural antioxidants that can neutralize free radicals in your body.
  • If your life circumstances permit, drink fresh vegetable juices on a regular basis. Freshly pressed vegetable juices provide a wide range of nutrients, including antioxidants, which are easily absorbed into your bloodstream. (To optimally support your blood sugar level, emphasize the use of greens like romaine lettuce, kale, and celery, and use only small amounts of sweet vegetables like carrots and red beets. Consider using a high quality super green food product if you don’t have time to make vegetable juices on a regular basis.)
  • Eat fruits that are rich in antioxidants, Enjoy Life fruit antioxidantsuch as blueberries, pomegranates, raspberries, blackberries, strawberries, cherries, goji berries, papayas, mangoes, watermelon, and olives.
  • Don’t overeat. Since free radicals are produced by your regular metabolic activities, overeating results in excessive free radical formation in your cells; these free radicals can spill out into your blood, and eventually damage your tissues.
  • As you try to minimize the negative impact that free radicals can have on your health, don't forget the importance of acquiring restful sleep and striving to be emotionally balanced; a well rested body and a balanced nervous system are two of the most important requirements for a strong immune system that can protect your health against excessive free radicals.
  • Because many fruits and vegetables are grown in depleted soils, sprayed with pesticides, and harvested well before they are ripe, it may be wise to supplement your diet. Antioxidant supplements are widely available. Not all of them are equally effective. Also be aware that too much of certain antioxidants (vitamin E for example) can have harmful effects.




  • Many additional interesting (and many academic) articles on free radicals and means to combat them can be found at: http://www.healthcare.uiowa.edu/research/sfrbm/virtual.html






    References
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    6. The oxygen molecule is a stable diradical, best represented by ·O-O·, which is stable because the spins of the electrons are parallel. The ground state of oxygen is an unreactive spin-unpaired (triplet) diradical, but an extremely reactive spin-paired (singlet) state is available. (return)
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    antioxidant biochemistry





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    antioxidant biochemistry
    antioxidant biochemistry