MAG-pie Alert!… #13 TOXICITY OF IRON
By the end of THIS, you’ll be begging for more, AND lamenting the cramping in your “Hang 10!” Toes!… 😉
I realize that the vast majority of folks frequenting Facebook site are simply looking for “answers” to their ailments. I get that, truly I do, and it’s why I spend the MAJORITY of my time interacting with clients — the world over…
But my passion is to understand HOW & WHY ALL this misery & chronic disease came about, and make sure that I do enough to impart that information & insight onto the “MAG-pies” and “MAG-nets” who grace this august body of healers helping each other…
In my wildest dreams, I never would have imagined three years ago — yes, it’s been 3 “D”og Years of MAG activity for me & the original founders of this mineral-based group of contrarians to convention — that we would have grown this BIG, nor have tackled SOOOO MANY issues. It’s amazing what holding a MIRROR up to “the story” does to reveal the “truth…”
Well, this Post is more of same… I want folks to better understand why I’m not only gaa-gaa about Maggie, but also a VITAL protein/enzyme produced in our Livers & Brains: Ceruloplasmin (Cp). If the Sun is the “center” of our Universe, I’m coming to regard Cp as the “Sun” of our universe of metabolic activity.
For those that think this is merely “another” protein, you’ll find this a fascinating read to better understand the depth and complexity of this protein that has Ferroxidase enzyme activity.
1) Structure & function of Ceruloplasmin:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483498/pdf/d-63-00240.pdf
And what is even more fascinating is to know that Holmberg & Laurell, the discovers of this protein in 1941, identified it to have 8 Copper ions, and that was the case through the 1970’s in the literature. And then, suddenly the number of Copper ions dropped to 6-7, and now it’s recognized that there are ONLY 6 Copper ions. The re-calibration of the # of Copper ions is hardly due to “superior” diagnostic techniques…
Now anyone who knows me or knows this Group understands the position to STOP the mindless “D”ementia in supplementing Hormone-D. One of the MAIN reasons is laid out in this article that highlights the VITAL importance of Retinol and Retinoic Acid — we know this as animal-based Vitamin-A — in jump-starting the production of Cp. Given that Vit-A & Hormone-D are biological antagonists, it’s impossible to do so when “D”rowning our Liver in that vogue supplement that is wildly myth-understood…
2) Importance of Retinol in producing Ceruloplasmin:
http://jn.nutrition.org/content/117/9/1615.long
And it’s well chronicled in the literature that Ceruloplasmin (Cp) is the biological agent to keep Iron in a proper valence (# of electrons), and mostly importantly, keep it moving in & around the cell. The scientists like to refer to it as “cellular Iron efflux,” but that’s a fancy way of saying “keep it moving!”
That’s the IDEAL state for Iron… It is NOT meant to be “STORED” and measuring Iron in its storage state — via the Ferritin molecule — makes NO sense at all. It’s akin to selecting a car based SOLELY on the size of the Trunk, and IGNORING the size & efficiency of the engine, AS WELL AS the overall handling of the car… (Who does THAT make sense to?!?…Selecting a car based on its Trunk?…)
And what’s also known is that Ceruloplasmin (Cp) elevates in response to Inflammation. This is a biological certainty that has been encoded going back millennia of millennia… And now, BIG Pharma is seeking to apply the same MYTH-information strategy re Cp that kept us kidnapped for 60 yrs re Cholesterol. They want us to see Cp as the BAD guy, and do what we can to “lower” it… Which makes absolutely NO sense, but its elevation is consistent, particularly during an Inflammatory state.
And what they are forgetting to tell us is that Ceruloplasmin must be folded properly and have optimal amino acid composition to FUNCTION FULLY as an Enzyme… And the enzyme of choice is Ferroxidase, which is the active component of Cp that REGULATES Iron status and Iron movement…
And this was MOST confusing until I came across pearl yesterday and learned WHY Iron has to be in a certain valence to TURN OFF the activity of a KEY enzyme that used by neutrophils to KILL bacteria.
3) Ferric Iron (Fe++) Inactivation of Myeloperoxidase (MPO):
http://www.jbc.org/content/234/9/2486.full.pdf
What has also become clear is that “Inflammation” is actually an immune response to an “infection,” but WITHOUT the Pathogen!! You might want to re-read that sentence again, slooooooowly, to understand what “Inflammation” is… (It’s also important to know that LACK of sufficient Magnesium is the cellular state that TRIGGERS the Inflammatory Cascade…)
And then the universe dropped this pearl into my lap recently:
4) Cp is an Endogenous Inhibitor of Myeloperoxidase (MPO):
http://www.jbc.org/content/288/9/6465.full
So, once again, Ceruloplasmin comes to the rescue to regulate, or modulate the MPO response. That is HUGE, and it makes sense that biologically it’s coming to the scene of the crime, whether it’s got the enzyme capacity or not. It’s almost like “muscle memory” only this is “immune memory…” And what Cp is doing is MANAGING the Iron to stay in the right state and stay active…
Now, for those seeking to understand WHY there’s always a death or two at a Marathon (Rick Malter, PhD…) this puts an entirely different spin on it. Endurance exercise DEPLETES our minerals, especially Maggie, and that sets the stage for an Inflammatory response in our heart, which then triggers a RISE of MPO, and if were SHORT on Ceruloplasmin, the degradation of Heme releases Mo’ Iron, which accelerates Lipid Peroxidation (we know that as “Plaque”…) and it’s good night, Irene for that Cp-deficient runner. And know that chronic “Stress!” is a MAJOR cause of under-production of Cp in the Liver…
5) MPO is elevated following a Marathon, endurance exercise:
http://ajcp.oxfordjournals.org/content/126/6/888
6) MPO >> HOCl- >> Heme Degradation >> Iron Release…
http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0027641&representation=PDF
Well, here’s the punch line…
One of my colleagues/clients/fellow Iron researcher/friends, Maria Dolores Chagas Oliveira, has helped me see the light re HOW Ceruloplasmin is getting tweaked, and losing its Ferroxidase function. It is the being CAUSED by the “nitration of a key amino acid, Tyrosine.” Be careful, this is NOT for the faint of heart or anyone looking for a quick read:
7) Nitric Oxide, Oxidants and Protein Tyrosine Nitration:
http://www.pnas.org/content/101/12/4003.full.pdf
And what’s the BEST way to “Nitrate Tyrosine?!?”
Expose it to Superoxide radicals and NO2 that is CAUSED by excess, unmanaged Iron. This idea that we are “Iron deficient” is beyond ridiculous, despite the countless articles that say we are. Imho, it is absolutely just the OPPOSITE!
So, we’ve come FULL circle. Iron is THE “Stressor!” that is CAUSING excess loss of Maggie, and now we come to realize that it is the CAUSATIVE agent to create Oxygen Stress, AND Nitrogen Stress that is at the heart of neutering Ceruloplasmin, the very protein/enzyme that is ESSENTIAL to properly manage this toxic metal…
How Iron-ic is that?!?…
A votre sante!
MORLEY M. ROBBINS
See Facebook Discussion at:
https://www.facebook.com/groups/MagnesiumAdvocacy/permalink/942303632504373/
