Redox biology

Life of human beings depends on oxygen. Oxygen is essential to aerobic life, and it is in the same time, a toxic gas. Redox chemical reactions refer to REDuction - OXidation reactions; reduction is always associated with oxidation in a solution; electrons can NOT be freely roaming in a solution. In a solution (e.g., cell cytoplasm), electron transfer can occur from one molecule to another via 4 main ways: 

1. Directly as electron (e.g., Fe2+ + Cu2+ → Fe3+ + Cu+)

2. As hydrogen atoms (H): hydrogen contain 1 proton + 1 electron. It can donate its electron forming H+. The loss of hydrogen in body tissues is achieved by enzyme class called “Dehydrogenases

2. As hydride ion (H-): a hydride ion is a hydrogen atom contains 2 electrons (e.g., Acetalydehyde + Hydride = ethanol; pyruvate + hydraide = lactic acid)

4. Through direct combination with oxygen

In chemistry, “Combustion” usually involves a substance reacting with oxygen. The process of adding oxygen to a compound is known as “Oxidation” (Rusting). If you did the opposite, removing oxygen from a compound, the process is known as “Reduction

In biochemistry, the following are true:

Oxidation: a process of adding oxygen (O2), removing hydrogen (H), or removing electrons (é) into a compound

Reduction: a process of removing oxygen (O2), adding hydrogen (H), or adding electrons (é) into a compound

Redox homeostasis state is like the pH or the osmotic pressure, representing the chemical characteristic s of the intracellular environment. Each cell in the body has a certain store of electrons (Redox state), and a frequency, which determine its function. Redox hemostasis depends on the balance between what the cell is exposed to from free radicals and its electron store’s ability to neutralize their effects 

Excess oxidation is the basic abnormality behind many chronic degenerative disorders, cancers, and diabetes mellitus, where oxidation affects the DNA, lipids (Lipid peroxidation) and proteins (Carbonylation), leading to cytotoxicity

Reactive oxygen-nitrogen species

 (Free radicals)

Reactive oxygen species (ROS) is a term also frequently used in biology and medicine that simply defined as “Oxygen-containing” reactive species. Another group exists that contains “Nitrogen” and thus, is known as “Reactive nitrogen species” (RNS). ROS/RNS are generated from various endogenous cellular sources, such as NADPH oxidases and mitochondria. ROS/RNS are also produced from a variety of exogenous sources, including physical agents, xenobiotics, and biologic agents (e.g., viruses & bacteria)

The formation of ROS by mitochondrial electron transport chain is increased under various pathophysiological conditions, including tissue ischemia-reperfusion phenomenon and hypoxia. For example, nitric oxide is also generated in mitochondria via the action of mitochondrial nitric oxide synthase

Uncontrolled production of mitochondria-derived ROS/RNS has been implicated in diverse pathophysiological processes, such as tissue ischemia-reperfusion injury and neurodegeneration. ROS/RNS act as the only initial cause of the disease. Control of the ROS/RNS will prevent or stop the disease development

Examples of ROS include:

1. Superoxide (O2.-): commonly arises from reduction of oxygen by NADPH activation (e.g., inflammation)

2. Hydrogen peroxide (H2O2): is commonly produced by WBCs as a defense mechanism against pathogens. Also, it binds to the sulfhydryl group of enzymes causing their inactivation. It is typically detoxified by the enzyme “Glutathione peroxidase

3. Hydroxyl radical (.OH): is known as the most reactive ROS, and commonly formed from water body exposure to ionizing radiation and ultraviolet light (e.g., sun bath)

4. Singlet oxygen (1O2): is electronically excited form of molecular oxygen. It arises in cases of inflammation and lipid peroxidation

5. Peroxyl radical (LOO.): arises from lipid peroxidation (Some lipids are digested by peroxisomes)

6. Alkoxyl radical (LO.): arises from lipid peroxidation (Some lipids are digested by peroxisomes)

7. Lipid hydroperoxide (LOOH)

8. Peroxynitrite (ONOO-): is a dangerous ROS that typically detoxified by glutathione

9. Hypochlorous acid (HOCl):  is formed from the reaction of hydrogen peroxide and chloride catalyzed by phagocytic myeloperoxidase during inflammation. Under certain conditions, such as chronic inflammation, uncontrolled formation of hypochlorous acid may attack normal cellular biomolecules, leading to cell and tissue injury. It is detoxified by glutathione

10. Ozone (O3): is a gas in the stratosphere that protects animals on earth from solar irradiation. Ozone is also an air pollutant near the earth’s surface, where it is formed by photochemical reactions. Ozone is not a free radical, but has potent oxidizing capacity

The body’s anti-oxidant system

Electrons are antioxidant; as long as the body is full with electrons (e.g., in alkaline state in chemistry terms), the body is “Healthy”; that’s why, antioxidants are the most common types of “Terminators” for the chain reaction caused by free radicals. Antioxidants are donors of free electrons and used externally to reduce wrinkles on the skin and also internally to slow the aging

An antioxidant is defined as any substance that can prevent, reduce, or repair the reactive oxygen and nitrogen species (ROS/RNS)-induced damage to a target biomolecule. Antioxidants can be:

Endogenous (produced by the cells): glutathione, methionine, SAMe, ferritin, metallothionein, coenzyme Q, estrogen, α-lipoic acid, melatonin, uric acid, pyruvate …etc.

Exogenous (Derived from diet): vitamin C, vitamin E, vitamin A …etc.

Antioxidants normally can only donate one electron from each molecule. Instead, the endogenous flood of abundant electrons from bioelectrical machines can provide enough electrons to force a cancerous fermentation cycle production of ATP in the Krebs cycle back into a respiration cycle. This is the main mechanism in which these machines can provide anti-cancer effect

The body’s antioxidant defense system is composed of “Glutathione system”, with its supporting antioxidant molecules (Vitamin C, Vitamin E, Selenium, Cystine). Glutathione is an important, most powerful reducer agent in the body. It is a tripeptide composed of glutamate, cystein, and glycine. Gluathione is a scavenger used to detoxify drugs and peroxides (e.g., hydrogen peroxide H2O2), rendering them water (H2O) soluble. Oxidized glutathione is reduced by the enzyme “Glutathione reductase”, which uses NADPH as a cofactor

Oxidative stress


Oxidative stress is a term refers to a condition where the levels of ROS significantly overwhelm the capacity of antioxidant defenses in a biological system. Oxidative stress results in accumulation of hydrogen peroxide and free radicals, among other wastes. Oxidative stress condition is associated with oxidative damage to biomolecules, including proteins, lipids, and nucleic acids. Oxidative stress and inflammation are intimately related processes.

Free radicals are a type of “Unbalanced” molecule that has long been known to cause cell damage, and are able to initiate inflammation and to irritate nociceptors. Free radicals function as communication molecules that promote or sustain inflammatory reactions. They increase the activity of a substance called “Nuclear factor kappa beta,” which activates genes involved in inflammation, cancer, and other diseases. Free radicals also boost the activity of interleukin-6, another pro-inflammatory molecule

The main dangers arise from oxidative stress is that these positively-charged molecules tend to steal electrons from cells to neutralize themselves. Stealing electrons from lipids will results in “Lipid peroxidation”, transforming the lipid into “Rancid”, which is highly toxic to the body and evokes inflammation. In oxidative stress, “Glutathione depletion” is an early event leading to cellular death

Free radicals are responsible for many “Aging-features” and "Degenerative diseases" like Alzheimer's disease, Parkinson's disease, arthritis, cataract, cancer, multiple sclerosis, diabetes mellitus, and liver disease


Selected references

1. Naidu AS. Redox Life. 2013; Bio-Rep Media; 1st edition

 2. Halliwell B. Antioxidants in human health and disease. Annu Rev Nutr 1996; 16: 33-50