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How the Useful Molecular Oxygen that We Breathe May Turn Harmful
Molecular oxygen is involved in the metabolism of glucose to produce energy; that way it is useful
Molecular oxygen is useful and harmful
The form of oxygen we breathe that is useful is molecular oxygen, indicated as O22-. It consists of two atoms of oxygen with two unpaired electrons in its outermost orbital (path around the nucleus). The air around us contains 21% molecular oxygen.
There are other forms of oxygen: atomic oxygen, singlet oxygen and ozone. We may also breathe them but in small amounts and are not useful to us. Atomic oxygen and ozone are mostly found in the atmosphere, second layer above us and beyond. Ozone is produced by sparks of electrical gadgets like engine starters and electric fans. Singlet oxygen is produced by the body when ultraviolet rays strike the skin. It is also produced by chemotherapy drugs. Ozone and singlet oxygen are outrightly harmful.
Molecular oxygen is not directly harmful. Its two unpaired electrons spin in parallel direction. This spin makes molecular oxygen difficult to react with non-radicals. It will not react readily with an element that has no unpaired electron in its outermost orbital. Therefore, molecular oxygen does not directly inflict damage to most biological molecules and the human body will not burn. This kind of burning is different from one where you see fire, or smoke. This is what you see when you pour some amount of hydrogen peroxide (3% grade) on some drops of blood. The blood will bubble and disappear. Hydrogen peroxide is a derivative of oxygen.
Molecular oxygen as useful
Of the amount molecular oxygen that we inhale, about 75% of it is used up, the 25% is exhaled. We use molecular oxygen to produce energy called adenosine triphosphates (ATP). This oxygen is involved in glycolysis and in the cytochrome system, the process of energy production from glucose or blood sugar. This process is shown in the illustration above.
The process is like a waterfall whose energy is harnessed. At the head of the waterfall, two electrons taken away from two atoms of hydrogen fall down. The two protons that are former partners of these electrons stand by. Each electron follows its own path. As each electron falls, it produces ATPs. At the foot of the waterfall is molecular oxygen waiting for the falling electron. If molecular oxygen is absent, the cytochrome system backs up. No energy is produced and disease may result.
At the foot of the waterfall, one of the unpaired electron of molecular oxygen pairs up with one falling electron and two protons and make a molecule of water. One unpaired electron of molecular oxygen remains as is and makes a superoxide.
We need a lot of ATPs. One brain cell consumes 10 million ATPs per second. There are 60 trillion cells of our body. That means a lot of superoxides are also produced as by-products.
Molecular oxygen as harmful
Molecular oxygen easily propagates a radical reaction that had started (Halliwell, B. “The Proteosome: Source and A Target of Oxidative Stress.” Stefanis, L. and J. B. Keller. Editors. The Proteosome in Neurodegeneration. 2006:86). It propagates a small fire ignited by others into a conflagration, so to speak.
A polysaturated fat (like crab’s) combined with a reactive oxygen species (hydrogen peroxide) form a carbon-fat plus reactive oxygen species and atom of hydrogen.
This reaction continues as follows:
Carbon-fat plus molecular oxygen form fat and superoxide.
This compound of fat and superoxide is called peroxyl radical.
Peroxyl radical plus polyunsaturated fat form lipid peroxide.
Lipid peroxide propagates in chain reaction. This had engulfed a whole molecular oxygen intact. That means, lipid peroxide has two unpaired electrons that can do damage. The macrophage, component of the immune system, engulfs lipid peroxide and turns foamy that clings to the atheroma (Sharma, H. MD. Freedom from Disease. 1993). This is a benign tumor started by free radicals on the endothelium. That is why lipid peroxide adds to the plaque of arteries of the heart that may result in angina or heart attack.
Unsaturated fat can take the place of polyunsaturated fat. The low density lipoprotein (LDL) can also take the place of unsaturated fat. If chicken egg were cooked with the shell cracked oxygen will oxidize the LDL (67gm in the egg yolk) and turn it into lipid peroxide. That is why egg should be pouched, soft boiled, hard boiled not scrambled.
Superoxide, the master free radical
Let’s get back to superoxide that is a by-product of the metabolism of glucose. Superoxide is a free radical. It reacts with another free radical, nitric oxide that is produced by the endothelium (inner wall) of the artery. The endothelium produces three enzymes: endothelium nitric oxide synthase that produces nitric oxide (NO/eNOS). This is another free radical that signals the endothelium to dilate and allow more blood flow. This time, NO/eNOS is useful. Another enzyme is neuron nitric oxide synthase that produces NO/nNOS; this also dilates arteries. The third enzyme is inducible nitric oxide synthase that produces NO that can kill cancer cells and healthy cells. (More of this below).
The reaction between superoxide and nitric oxide results in peroxynitrite (ONOO-), a reactive oxygen species (ROS). Peroxynitrite also catches nitric oxide three times faster than superoxide does. In short, superoxide and peroxynitrite deplete nitric oxide. That is detrimental for a person with a heart disease. Such depletion may result in angina or heart attack.
What makes it worse for a person who has a plaque is that the artery with an injury like atheroma or plaque does not produce nitric oxide synthase resulting in lack of NO/eNOS. This can be remedied by the supply of nitroglycerin (Isordil, Imdur).
As master free radical, superoxide has other siblings like hydrogen peroxide, hydroxyl radical, alkoxy radical. These are ROS that act like free radicals in a harmful way.
Our body's counter
Our body has built-in counters (antioxidants). The superoxide dismutase (SOD) attaches one proton to one oxygen atom and one atom of hydrogen to make hydrogen peroxide, a ROS. That makes the situation worse - wait. Glutathione peroxidase adds one electron to hydrogen peroxide and turns it into safe water. Glutathione reductase recycles glutathione peroxidase. Glutathione synthase makes glutathione from nutrition, fruits and vegetables. Manganese SOD is the variety that catches the superoxide from metabolism of glucose.
Built-in antioxidants can be supplemented with vitamins A, C, E and B complex. Other supplements are melatonin and coenzyme Q10.
I have several Hubs discussing how free radicals and ROS are produced, their sources and how they can be countered. I also discuss there how free radicals and ROS cause heart disease, cancer and other degenerative diseases like arthritis, osteoporosis, diabetes, motor neuron disease, emphysema and more.
The principle involved is that antioxidants supply the electrons to satisfy the hunger of free radicals or ROS for electrons. There must be a balance between free radicals and ROS on the one hand, and antioxidants on the other. This way oxidative stress in the body is prevented.
Inducible nitric oxide
I can't resist to repeat what I have discussed in three Hubs about the use of nitric oxide as cure for cancer.
Nitric oxide is a free radical that can kill healthy and cancer cells. It can be tapped to cure cancer in a method called gene therapy that is a technology in biotechnology.
To start with, our body produces inducible nitric oxide synthase (iNOS) but in small amount. For use in killing cancer, it should be more concentrated. The gene that controls the production of iNOS once inserted in the chromosomes of cancer cells, will produce nitric oxide that kill cancer cells. iNOS must be delivered to cancer cells in a very specific manner so that healthy cells will not be affected. The courier is protein envelop of a virus. Cancer cells exude carcinoembryonic antigens (CEA) that serve as maker. To enhance the specificity of delivery, the surface of the cancer cells must be modified such that they admit only the courier. This surface modifier is an antibody. The genes of the virus protein envelop and that of the antibody are cloned likewise. Then the genes of iNOS, protein envelop and antibody are bound together with hydrogen and sewed up together by the enzyme ligase. The result is a recombinant DNA. This recombinant is administered like a vaccine to the cancer patient. The courier will land on cancer cells only whose surface had been modified and that shows the marker (CEA).
Once the gene of iNOS is incorporated in the chromosomes of cancer cells, nitric oxides are produced that kill cancer cells.