User Tools

Site Tools


freeradicals

Free Radicals



Definition


A free radical can be defined as a reactive chemical species. The reactivity is due to molecules having one or more unpaired electrons. For living organisms, these radicals can be beneficial at low levels or deleterious if in excess. A number of different types exist, these being based on either oxygen, nitrogen, carbon or sulphur. This limited introductory discussion will only focus on the more abundant and important oxygen-based free radicals.

Reactive Oxygen Species


Reactive Oxygen Species (ROS) are of particular concern to us oxygen breathing active carbon units. At low levels, ROS play a key role as messengers in normal cell signalling, replication and apoptosis (cellular death process). Internal mechanisms are able to regulate the amount of ROS and our biological systems remain in a balanced state. If, however, the levels of ROS increase, our systems become unbalanced, and oxidative stress will induce varying amounts of damage to lipids, carbohydrates, proteins and nucleic acids.


ros_.jpg
Figure 1. Some of the more important oxygen-based free radicals. ref


The superoxide anion is the most common and is generated in the mitochondrial electron transport chain process. About 1 to 2 % of the overall process results in this anion (-ve charged ion), mainly from 'leaky' complex I and III reactions.

The hydroxyl radical is the most reactive and does damage close to the site of origin. Most of it is formed by the *O2- → H2O2 → *OH reaction sequence. It can also be produced by water being ionized by radiation or by a metal-catalyzed breakdown of H2O2.

Hydrogen peroxide is the least reactive of the species. Its danger lies in the fact that it can diffuse across membrane barriers and then form a hydroxyl radical which is very reactive.

Sources of ROS


Endogenous (internal) sources
Mitochondria (electron transport chain)
Peroxisomes
Cytochrome P450
Lipoxygenases
Phagocytes (respiratory burst)
NADPH oxidase
Excessive physical exercise


Exogenous (external) sources
UV / Ionizing radiation
Drugs / Chemotherapy
Inflammatory cytokines
Environmental toxins (air/water pollution, smoking)
Alcohol / Solvents
Metals


Internal sources of ROS play important roles in normal cellular functions such as fighting infection, regulating signal pathways and facilitating normal reproductive systems. The mitochondria are considered the dominant internal source for ROS generation.

External sources present an additional load that overload our inherent defense systems and result in excessive damage.

ROS Effects


ROS related health conditions
chronic inflammation
autoimmune diseases
sensory impairment
cardiovascular disease
cancer
fibrotic disease
obesity
neurological disorders
infectious diseases


If not kept in check, oxidative stress can be responsible for the introduction of a number of chronic and degenerative disease conditions.

We also experience a lot of accumulated damage as a natural part of the aging process. A number of theories relating to the aging process have emerged over the years. These are frequently controversial as it is hard to discriminate between cause and effect. Theories of aging generally fit into either a damage- or programmed-based grouping. Damage theories state that aging is a result of accumulated damage as a result of interactions with the environment. Programmed theories argue that aging is a response to genetic programming. In this discussion, we're focused on the free radical influence on aging and how to interrupt and minimize the effect.

Antioxidant Reactions


Enzymatic antioxidants
Name Reacton Functions
superoxide dismutase (SOD) 2O2* - + 2H → H2O2 + O2 superoxide → hydrogen peroxide
Catalase (CAT) 2H2O2 → 2H2O + O2 hydrogen peroxide → water
Glutathione 2GSH + H2O2 → GS-SG + 2H2O hydrogen peroxide → water


The body naturally protects itself from ROS by using enzymatic antioxidant mechanisms. In these reactions, oxidative products are converted to hydrogen peroxide and then to water. This is a multi-step process where enzymes work in conjunction with Cu, Zn or Fe co-factors. Our levels of these enzymes naturally decrease as we age.

Natural non-enzymatic antioxidants
Name Solubility Reaction Function
vitamin C water RO* + C6H7O6- → ROH + C6H6O6 Hydroxyl radical → water
vitamin A oil lipid radical termination
vitamin E oil LOO- + α-tocopherol-OH → LOOH + α-tocopherol-O- lipid radical termination
bioflavonoids metal ion chelation
carotenoids oil peroxyl radical scavenger


Non-enzymatic antioxidants are obtained via dietary supplementation. They work by interrupting free radical chain reactions.

Antioxidants can be categorized as being water or lipid (oil) soluble. Water soluble antioxidants are present within cellular fluids and lipid soluble antioxidants locate within cell membranes.

References

freeradicals.txt · Last modified: 2019/03/19 19:44 by lisa