This post started by the suggestion of @lesshorrible in his post NSAS Idea Suggestion #5 - Antioxidant Hype.
However, @csusbgeochem1 did his version on the idea too, so I will be focusing on the Medical View of free radicals. You can also check his post as well! (The link will be in the end of the post).
Without more delays, let's dive into it!
Our cells do a lot of functions to maintain the precious state of homeostasis. However, all of this functions require some quimical metabolic processes which can produce a lot of unstable chemical species.
Free Radicals
Superoxide, Oxygen as we know it with 1 extra electron - by DoSiDo, CC BY-SA 3.0
Free radicals are a type of molecular compound that has 1 unpaired electron in an atomic orbital, which makes them very reactive as they can either donate or accept one electron from any molecule or atom. In health, the most important are Reactive Oxygen Species (ROS) & Reactive Nitrogen Species (RNS) which are derived from metabolic processes that occur with Oxygen & Nitrogen.
We have a double-edged sword here though, as this property can make them very dangerous. They can bind any molecule and change their properties with the pontential of rendering them useless.
However, they have other helpful functions! Our body could use them to harm pathogenic bacteria and kill them or can be used as cell-to-cell signalling.
As you may expect, our body is not the only source of ROS. Pollution, combustions and most importantly the cigarette smoke introduce a large number of them in the airways!
But... how are they formed?
The answer is: RedOx reaction.
Oxidation of Sodium & Reduction of Fluorine to form Sodium Fluoride - by Wdcf, CC BY-SA 3.0
I know, it sounds like the title of a movie (let's call it: Chemistry RedOx), but it is an actual chemical process in which:
- One species undergoes reduction, or gaining an electron (or loses oxygen)
- While the other undergoes oxidation, or losing an electron (or gains an oxygen)
These reactions happen with one compound performing reduction and the other performing oxidation.
It was called that way as they were first discovered to happen with oxygen.
As you can see, the reaction of electron exchange can lead to the creation of chemical species which will have an extra electron than what is its normal amount.
For some atoms they just create an anion and end of story. But for some other compounds like Nitrogen or Oxygen, their creation can lead to a disastrous highly reactive species, hence their name in health. Other causes of their generation can be radiation, as it can "move" electrons easily.
Overview of origins of ROS - by Erica Novo and Maurizio Parola, by CC BY 2.0
Production can be happening in different ways and in different parts:
- Inside the mitochondria as part of the last steps of oxidative metabolism of sugars.
- Intracellularly by NOXs (NADPH oxidase), which are enzymes from different types which have the function to produce ROSs, present either in healthy cells (leukocytes) or in pathological circumstances.
- Activity of COX and LOX for the oxidation of Arachidonic Acid to produce inflammatory factors, producing ROS
All of them have a name of oxidase as they cause oxidation of the substance, relying on a RedOx reaction.
At this point, you the Stemian reader will be thinking "they are bad, they should be removed!". But it is not what it seems. They can act by some mechanisms and can be really benefitial for the cells themselves!
Next, we are going to see in detail the different effects or functions that they have in our cells.
Inmune Function
The Leukocytes in 3D - by BruceBlaus for Blausen.com, CC BY 3.0
Phagocytosis (Endocytosis) - by Raffmarra, Public Domain
Our precious inmune cells, the leukocytes, are constantly scavenging in our body for any pathogen (bacteria). When they find it, the first thing to do is engulf it in a process call endocytosis. After that, they mix that phagosome with a comparment called lysozome, which has digestive enzymes and ROS so they damage and kill the bacteria or fungi, even though in viruses is not entirely clear.
The lack of these ROS in some people make it more difficult to kill pathogens and hence, they are susceptible to more infections. The name of that illness is called chronic granulomatous disease or CGD.
Inflammatory Function
Inflammation process - by Dr. med. Mario Schubert, CC0 1.0
ROS can also have some fuction as to give the signal of activation of inflammation.
This increases the NLRP3 amount, which is a signal sensor to regulate oxidative stress in the cell. NLRP3 starts a signal transduction inside de cell which in the end activates T-cells and Macrophages. These activated leukocytes then induce the activation of Prostacycline (a molecule that causes inflammation).
In this way it alerts all cells in the surroundings to prepare for any kind of oxidative stress.
Ischemia
NADP+ used in NOX by NEUROtiker, Public Domain
Ischemia is the depravation of Oxygen from a tissue for a long time.
It has been proved that NOXs has been present in ischemic tissues as there is no regulation of the enzymes which use Oxygen. For that reason, this can lead to heart failure and in big blood vessels, the endothelium can be very damaged, leading to poor blood movement to further vessels.
However, it was found that ROS given by NOX determinate endothelial function after ischemic injury.
Patients with CGD (reduced ROS production in inmune cells) had no effect when ischemia appeared while healthy patients showed lower reduction of blood flow in response to ROS damage.
Aging
Aging - CC0
There is one theory called the "mitochondrial free radical theory of aging". It says that aging is "partly caused" by the damages of molecules by ROS produced in mitochondria activated only during RedOx processes of respiration to obtain Energy.
It was shown in rats that by restricting diet by 60%, their life span could be extended for a significant amount of years.
But... what about humans?
We are a type of animal that tends to overeat or eat excessively caloric food, so our mitochondrial metabolism is actually working more & producing ROS that can cause damage. According to the theory, this is an "accelerator" of the aging process.
Other theories suggest that ROS just modulate the aging process by mediating the responses of stress.
Unfortunately for us, further investigation is needed to know what is really happening.
Bottomline is however, that we should eat less in excess if we want to live longer. It is an advice difficult to accomplish as even I don't follow it entirely.
Neurological Function
Neuronal connections - CC0
It has been proven that CGD patients show decreased cognitive function in comparison to a normal healthy patient. The reason being that ROS affect somehow the process of apoptosis, meaning that they may have a cell-to-cell communication role!
Also, ion channels & transcription factors have been observed to act under the influence of ROS. However, the inner workings are still unclear.
Important to note is (yet again) the presence of ROS produced by NOX enzymes.
Their overproduction can be neurotoxic and lead to illnesses such as dementia & also surprisingly Parkinson's disease as neurodegeneration of dopaminergic receptors can be present.
We have seen that ROS can be helpful, but also harmful. So, in the case of overproduction, it would be recommended to take antioxidants to remove them. But what are they and how they work?
Later we will analyse if they are actually needed or if is it just marketing.
Antioxidants!
ROS & their generator mechanisms are the targets here. The whole point of them is to decrease the amount of ROS & the mechanisms that generate them.
Target 1: Mechanisms of ROS generation
Blue = active site, Black = substrate, Green = inhibitor - by Thomas Shafee PhD., by CC BY 4.0
As it was mentioned before, NOXs are a type of enzyme that produce ROS. But as any enzyme, it can be stopped by the use of an inhibitor. By doing this, we actually eliminate the problem entirely.
The important part of inhibiting enzymes is one of their properties: their specificity! If we use a blocker (a molecule that mimics the substrate and blocks the active site ) we can block the entirety of the enzymes!
Besides all of this, we have to bear in mind the adverse effect that this can cause in other tissues like brain, where ROS serve as signalling. So inactivating NOXs there would cause more damage than heal.
Target 2: ROS themselves
If we cannot destroy the mechanisms that produce them, we can at least destroy the ROS themselves.
To make the mechanism more simple we are going to focus in Vitamine C even though there are others like Vitamine E that can help in ROS elimination.
Ascorbic Acid (Vit. C) by Yikrazuul, Public Domain & Dehydroascorbic Acid by ChemDraw, Public Domain - Extras done be me
The reaction is very simple, once the ROS enters into contact with one molecule of Ascorbic Acid, this transforms into Dehydroascorbic Acid and releases a Hydrogen atom and an electron while transforming the ROS into a normal non-reactive molecule.
Conclusion
ROS are a type of unstable molecule that usually is known for causing damage but surprisingly it has been used by our cells for more than just self-defense against pathogenic invasors.
We usually think about consuming antioxidants to prevent ourselves from that kind of damage, but excess of them could literally mess up some of our biological processes by lack of ROS which can be the case in CGD patients. On the other side of the coin, too much ROS can cause irreversible damage, as it can be seen with patients who are smokers.
Antioxidants are usually "produced by our body", although in the case of Down Regulation it can happen that they are produced in less amount so we don't run out of all the ROS. But also ingested natural antioxidants can be helpful in case of a deficiency or as a general basis. But only if it is not in excess. And even with fruits only for vitamins could be more than enough
I am not very good at analysing economics, but according to this paper (listed in my References), by 2020 it is expected that the whole industry of antioxidants will see a gain of 3.1 Bn of US$.
My opinion?
By having an equilibrated diet we should be having, we can avoid the trouble of excessive ROSs and to be honest, I don't really think that antioxidants are necessary unless you need to have a restrictive diet like in the case of Phenylketonuria or in cases you have a deficient enzyme or metabolic process which impairs the ROS elimination.
But of course, antioxidant companies have to make some ca$h from somewhere right?
What do you think?
Closing
I know, I know. This post took forever to arrive. I had some stressful time at University as work starting to come up out of nowhere and on top of that I had to travel to my country to visit family.
Check out also
- @csusbgeochem1's post about Superoxide Dismutase
and - @lesshorrible's NSAS ideas and the one that spark this post: NSAS Idea Suggestion #5 - Antioxidant Hype
My apologies to both for making them wait so much for this post. But also thank you both for being so patient with me. I will owe you one!
Also, I will try to be more active on Zappl to give more tiny facts, to give any update on how (bad) I am doing with my time, and finally start experimenting with more content here on Steemit.
Yes, I am alive and active again!
As always
This is @deholt, signing off!
Edit: Clarity and correction
References
- Forgotten Radicals in Biology - by Rochette Luc & Catherine Vergely in PubMed
- Reactive Oxygen Species – Wikipedia
- Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling - by Paul D. Ray, Bo-Wen Huang, & Yoshiaki Tsuji in PubMed
- What are Free Radicals? - by Dr. Edward at Global Healing Center
- Reactive oxygen species: from health to disease – by Brieger K. (1), Schiavone S, Miller FJ Jr, and Krause KH. In PubMed
(1) = Department of Pathology and Immunology, University of Geneva Faculty of Medicine and Geneva University Hospitals, Switzerland - NOX enzymes and the biology of reactive oxygen – by J. David Lambeth for Nature science magazine
- Mitochondrial Reactive Oxygen Species (ROS) and ROS-Induced ROS Release - by Dmitry B. Zorov, Magdalena Juhaszova, and Steven J. Sollott at PubMed
- Bioactive Lipoxygenase Metabolites Stimulation of NADPH Oxidases and Reactive Oxygen Species - by Kyung-Jin Cho [1], Ji-Min Seo [1], and Jae-Hong Kim at PubMed by equal contribution
[1] = at College of Life Sciences and Biotechnology, Korea University - Reactive Oxygen Species: from health to disease - by Brieger K [1], Schiavone S, Miller FJ Jr, Krause KH.
[1] = Department of Pathology and Immunology, University of Geneva Faculty of Medicine and Geneva University Hospitals - NLRP3 inflammasome: From a danger signal sensor to a regulatory node of oxidative stress and inflammatory diseases - by Amna Abderrazak, Tatiana Syrovets, Dominique Couchie, Khadija El Hadri, Bertrand Friguet, Thomas Simmet & MustaphaRouis at ScienceDirect.com
- Extract from: Antioxidants Market - Global Industry Analysis, Size, Share, Growth, Trends and Forecast 2014 - 2020 - by Transparency Market Research