How Unbound Iron and Copper Cause Oxidation and Pathogenic Bacterial Diseases
Nutritional trace minerals such as iron, copper, zinc, and manganese, are involved in many crucial biochemical processes for the survival of all living organisms.
They are required cofactors for many proteins, including enzymes that make up the bulk of all biochemistry.
Not only that, but they are also cofactors for storage proteins such as ferritin, as one example, and the transcription factors that enzymatically help translate DNA to messenger RNA.
Therefore, all biological life from the most straightforward one cell bacteria including bacterial pathogens all the way up to the complexity of multicellular life forms, like humans, require these transitional metals—or life would cease to exist.
Even the enemy, your bacterial pathogens, must acquire metal ions to replicate and survive inside of you.
Your body, in turn, employs a multitude of mechanisms to limit the pathogens access to the nutrient metals in a process known as nutritional immunity, a term coined in 2012 by the researchers of Hood and Skaar.
The point being is that for the bacteria to colonize in your terrain, it is dependent upon bacteria's ability to obtain the nutrient minerals.
Nutritional immunity is a process by which your body, through a very sophisticated process mediated through quorum sensing, transporters, chaperones, and membrane facilitators, will sequester the trace minerals to limit the pathogens from gaining access to the mineral resources.
In fact, we could say there is a war for the resources going on, as the pathogens and your cells are competing for the metals.
However, this time, it's not the gold or silver, but it is the copper, iron, zinc, and manganese that become the heralded prize.
During infection, your nutritional immunity kicks in to produce proteins that can chelate metal ions and, thus, can restrict the availability of these essential metals from the invading pathogens.
For example, Calprotectin is one such factor that has broad-spectrum antimicrobial properties based on its ability to sequester zinc and manganese at the site of infection.
Also, other strategies that offer significant defense mechanisms include our body's ability to cage and lock up the cations, such as copper, iron, manganese, zinc, as well as chromium, cobalt, and molybdenum; this is what I call ‘The Metal Containment Systems.’
These containment buckets exemplify the importance of nutritional medicine coupled with detoxification strategies, which can tip the scales of balance to a more favorable position in order to avoid the onslaught of oxidative damage, the engine of disease.
Your metal containment compartments of notable mention are ceruloplasmin, metallothionine, alpha-lipoic acid, ferritin, lactoferrin, hepcidin, glutathione are the standouts that come to mind.
These containment storage proteins can be thought of as your mineral cages to lock up and secure your cation transitional metals.
However, since copper is my favorite mineral and because she is also the most electronegative of the transitional nutrient minerals, she deserves special attention.
Currently, in the world of biochemistry, it is a known fact that both copper and iron are the league leaders when it comes to producing the formation of ROS (reactive oxygen species) via Fenton Chemistry. [H.J.H Fenton discovered in 1894 that several metals have a special oxygen transfer properties which improve the use of hydrogen peroxide. Some metals have a strong catalytic power to generate highly reactive hydroxyl radicals (OH). Since this discovery, the iron catalyzed hydrogen peroxide has been called Fenton's reaction.]
However, all transitional metals (Cu, Fe, Mn, Mo, Cr, Co, Zn) are toxic at high intracellular concentrations to all life forms as they disturb and perturb redox reactions by producing highly reactive hydroxyl radicals, which are the most potent oxidizing radical likely to arise in biological systems.
The correct ratio and concentration of these transitional metals are pertinent to redox reactions, which, in essence, is the transfer of electrons from one molecule to another, as all life is driven by redox chemistry.
When Cu and Fe transfer their electrons from the metal to substrate, you could say they are the most redox-active metals in a biological system, and this is precisely when redox chemistry produces excessive reactive oxygen species that are very harmful and are at the heart of damaging DNA bases, lipid peroxidation, and altered calcium metabolism.
What that should mean to you is that ROS is the impetus driving your degenerative diseases like the multitude of cancers, neurogenerative brain diseases, plus all of our chronic diseases.
Typically, we think reactions involving iron are the most detrimental to health, but counter-intuitively copper is more toxic because it can induce oxidative damage via two mechanisms.
As I previously alluded to, copper and iron both catalyze the formation of ROS via Fenton chemistry, which is mechanism number one.
Now, herein lies the difference because copper toxicity (high levels of free unbound copper) will significantly reduce the levels of glutathione.
So the second method is high levels of copper reduce glutathione.
This means that a decrease in glutathione, therefore, increases the detrimental effects of ROS, allowing metals to be more catalytically active, thus producing higher levels of ROS.
So copper, as I have said many times, needs to be exalted in its importance for a variety of reasons, mostly because it provokes more significant oxidative damages than Fe3+ due to a higher capacity of Cu2+ to nonspecifically bind biomolecules, mainly through thiol groups.
Remember, your ‘thiols’ are your sulfurs, and this is precisely why we are going to look at glutathione and copper as another factor in copper homeostasis.
Generally speaking, reduced glutathione (GSH) is a thiol, made up of three sulfur-containing amino acids.
Glutathione is a vital antioxidant protector of the intracellular and extracellular matrix and plays several crucial roles in the control of signaling processes, detoxifying certain xenobiotics and toxic metals, as well as other functions.
So to reiterate, GSH can help to reduce copper toxicity by directly chelating copper and by maintaining it in a reduced state, making it unavailable for redox recycling.
Therefore, to limit the reactivity of copper before it goes to work with the appropriate enzymes, the body sequesters copper using predominantly thiol-containing proteins and peptides: the most abundant thiol-containing molecule—glutathione.
After a tedious look at the studies to date, the findings suggest that GSH balance and copper homeostasis are functionally linked in the totality of copper metabolism.
Therefore, we should think about GSH as another ally to consider for our copper toxic population.
Also, I should mention other antioxidants are vital for metal homeostases such as vitamins A, C, E, and the flavonoids such as beta carotenes, lycopene, quercetin, and other substances of this nature.
The vital point that must be underlined and highlighted is that metal concentration within cells must be highly regulated and carefully maintained to avoid both deficiency and toxicity for both the host, that being you, and the bacteria.
All organisms require mechanisms for sensing small fluctuations in metal levels to maintain a controlled balance of the acquisition of metals into the cells as well as arrangements for removing the minerals from the cells.
Moreover, the same metals that drive our biochemistry, such as copper, can also be used as a host defense mechanism to promote bacterial killing.
The critical point to understand is that the crucial process that drives bacterial infectious diseases is when the pathogenic bacteria acquire metals, while your supply of minerals becomes limited and restricted.
Nutrient limitation by your cells and nutrient acquisition by pathogenic bacteria are, therefore, crucial processes in the pathogenesis of bacterial infectious diseases.
This is why we need to monitor the nutrient transitional metals because they are toxic at high concentrations.
Therefore, knowing the status of these transitional metals makes the use of serial HTMAs ever so crucial in today's environment so that we can intelligently adjust our mineral programs to achieve balance, even in the age of toxicity.