Antioxidants and Free Radicals

- Bruce Ames, Ph.D. at University of California, Berkeley estimates that every single one of our trillions of cells suffers about 10,000 free radical hits daily! (Ames, 1993)

We know that glutathione is the master antioxidant.  We read and hear about antioxidants and free radicals them all the time, but just what are they? The simple answer is that antioxidants are substances that protect our cells from oxidation (by free radicals). 

Let's look at what free radicals are. Molecules are composed of atoms bonded together, via the sharing of electrons. Generally, atoms exist in pairs, with each electron of the pair having an opposite spin to the other. When a molecule is split, two things can happen. First, the electrons can stay together. When this happens, we say the molecule has ionized. For example, table salt, which is Sodium Chloride (NaCl), ionizes into two charged ions, specifically a sodium ion and a chloride ion. In this case, the Chloride received the electron pair, and the Sodium lost it. The other thing that can happen is that the electron pair is split. This leaves a highly reactive atom (a free radical), seeking to steal an electron, which sets up a domino effect of electron stealing. 

Antioxidants work by offering easy electron targets for free radicals.

Each time you are confronted by the threats in the outer circle of the diagram free radicals are released. The natural reserve of glutathione in the body breaks down under the assault. The effects of oxidative stress are so critical in fact that a new field of medical science has emerged, called 'Free Radical Biology' which studies the long list of diseases caused by it. Today it is known that antioxidants help diminish cell damage, slows the harmful effects of aging and lessens the threat of disease. Oxidative stress can be minimized by raising intracellular GSH levels.

If the free radical is not neutralized by an antioxidant it can wreak all sorts of havoc in our bodies. Current research, for example, is pointing to the fact that it is not only the presence of fat in our bodies that leads to plaque formation on our arteries, but the oxidation of fat by free radicals. With cancer, the problem starts when free radicals chip away at the DNA of our cells, eventually causing mutations that lead to malignancies.

The antioxidants provided by vitamins work because they can donate electrons to free radicals, thus neutralizing them. However, this makes the vitamin molecule unstable, and now it needs an electron. This is sort of like passing a very hot potato from person to person until someone finds a place to lay it down. In our bodies, that place is glutathione.

The chemical equation gets fairly technical, but in the end glutathione donates an electron and becomes a stable molecule known as GSH. Glutathione can then be regenerated via an enzymatic pathway that involves lipoic acid. The details of the chemistry involved is beyond the scope of this page, but is well established in the scientific literature. Also well established is the fact that the glutathione antioxidant system is the most important system in our bodies when it comes to the destruction of reactive oxygen compounds (very potent free radicals).  (Meister, 1994) Glutathione is often referred to as GSH.

Glutathione In order to understand the mechanisms beneficial biochemical interactions and possible whey protein potential health benefits of WPC, a brief biochemical review of the protein Glutathione is required, since it is this protein more than any other that has been thought to provide a protective function for a number of organ systems, including the crystalline lens of the eye, the retina, prostate gland, and the immune system. a. Glutathione Synthesis For the body to produce Glutathione (GSH) six building blocks are required: L-glutamate, L-cysteine, L-glycine, magnesium, potassium, and 5' ATP. Two enzymes are also required and they are L-gamma-glutamyl-cysteine synthetase (equation 1) and glutathione synthetase (equation 2) and the reaction proceeds in the following manner: Mg 2+ (1) L-glutamate + L-cysteine + ATP---------> L-gamma -glutamylcysteine + ADP + P Mg2+ (2) L-gamma-glutamylcysteine + L-glycine +ATP-----------> K+ L-gamma-glutamylcysteinylglycine +ADP + P L-cysteine is the rate limiting substrate in this reaction12 , while the rate controlling enzyme for the reaction is L-gamma -glutamylcysteine synthetase(5). b. Scavenger Pathways The 2 major functions of glutathione are to detoxify hydrogen peroxide (H2O2) and other organoperoxidases (free radicals) and to defend against oxidation within cells via the Glutathione Redux Cycle, or more commonly referred to as the Scavenger Pathways(6,7). Glutathione plays it's role of "scavenger" through out the body. The role of scavenger is primarily accomplished through glutathione peroxidase (GSH px). The peroxidase interacts with the H2O(2) to reduce it to harmless water, thus limiting it's electron stealing capacity. This is illustrated in the following equation: (2) 2-glutathione-SH +ROOH ------> glutathione disulfide + ROH + H2O The disulfide is then reduced with the co-enzyme NADPH in the prescene of the enzyme Glutathione Reductase to yield the original glutathione compound. (3) glutathione reductase +NADPH + H+ -----------> 2-glutathione-SH + NADP - Many theories of aging and disease are based upon the interaction of the formation of free-radicals and the subsequent reduction in glutathione levels which allows for an accumulation of free-radicals to remain within a cell and organ or organ system. Free-radicals that remain within cells may cause cell damage, DNA damage and may even cause cell death, cancer transformation or loss of cell immunity to viral or bacterial infection.

GSH's metabolic functions include:

♦  Enhancement of Immune Function

♦  Elimination of Toxins

♦  Elimination of Carcinogens

♦  Antioxidant Cell Protection

♦  Protection against Ionizing Radiation

♦  DNA Synthesis and Repair

♦  Protein Synthesis

♦  Prostaglandin Synthesis

♦  Leukotriene Synthesis

♦  Amino Acid Transport

♦  Amino Acid Transport

♦  Enzyme Activity and Regulation

 

Where do we get these antioxidants? 

Nature provides these through fresh "whole" fruits and vegetables which are full of them.  Asparagus, avocados and walnuts are particularly rich dietary sources of Glutathione.  (It is important to eat only whole foods for optimal health.)  Some important ones to look for are vitamins A, C, E, and Selenium.  In the case of glutathione, the source is dairy in the form of whey protein isolates.  High quality nutritional supplements also provide effective antioxidants.

 

Cysteine Rich Whey Proteins, and their effect on Glutathione

Now that we've laid a foundation for the importance of glutathione, let's discuss the role of cysteine in glutathione synthesis.  The importance of cysteine lies in the fact that it is an essential precursor to the master antioxidant glutathione.

Glutathione (GSH) is a tripeptide (a very small protein) made up of three amino acids: L-glutamine (glutamatic acid), L-cysteine and L-glycine. The amino acid most important (known as the rate-limiting factor) is cysteine. (Deleve, 1991)

In order for cysteine to survive the trip from the mouth to your cells it must be a part of a larger protein. Without adequate cysteine, cells can't produce enough GSH and the body suffers on three levels: cellular oxidation contributes to general decline and aging, toxins accumulate in the body causing further damage, and the immune system is compromised, leaving the body vulnerable to disease.

However, there is a form of cysteine that is non-toxic, easily transported into the gut, and transferred into cells. This form is cysteine and is comprised of two cysteines joined together by a disulfide bond. Upon cell entry the cysteine is reduced to cysteine. (Droege et al., 1994)

Having established that cysteine is the crucial element in supporting glutathione production, let's return to our cystine rich proteins. Alpha-lactalbumin, lactoferrin and serum albumin are all high in cysteine. Serum albumin and lactoferrin are also high in the combined molecule of glutamine and cysteine (gamma glutamylcysteine) which can also be transported into cells. So, it is obvious that a product high in the non-denatured conformation of these three proteins is essential for increasing intracellular glutathione levels.

 

Side Note:  Glutathione is one of Dr. Clark’s favorite detox supplements because Glutathione helps the body maintain good health despite occasional low-level benzene exposure.

 

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