(Formerly #13)

This will be my last post for 2015.  I realize that the vast majority of folks frequenting this FB 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 and why all this misery & chronic disease came about, and make sure that I do enough to impart that information and 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 has not been just 3 years of MAG activity for me and the original founders of this mineral based group of contrarians to convention that we would have grown this big. Nor we have tackled so many issues. It is amazing how holding a mirror up to the story does to reveal the truth.

I want folks to better understand why I’m not only crazy about magnesium, but also crazy about a vital protein/enzyme produced in our livers and 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:
   Bento, I., et al. (2006). “Ceruloplasmin revisited: structural and functional roles of various metal cation-binding sites.”
   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2483498/pdf/d-63-00240.pdf?fbclid=IwAR30b7qKjfMy1HgGUeOIH3WAA0Aj6kUysY-Hv0OtQecIPvkhaAvD5n8YCGA
   What is even more fascinating is to know that Holmberg and Laurell, 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, I belive, is hardly due to “superior” diagnostic techniques.Now anyone who knows me or knows this group understands the position to stop the mindless dementia 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 which jump-starts the production of Cp. Given that Vit-A and hormone-D are biological antagonists, it’s impossible to do so when drowning our liver in that vitamin D supplement that is wildly misunderstood.

2. Importance of retinol in producing ceruloplasmin:
   Barber E.F., Cousins, R.J. (1987). Induction of Ceruloplasmin Synthesis by Retinoic Acid in Rats: Influence of Dietary Copper and Vitamin A Status.
   It is 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 and 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!”Keeping it moving is 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 is akin to selecting a car based solely on the size of the trunk, ignoring the size and efficiency of the engine as well as the overall handling of the car. Who does that? Selecting a car based on its trunk?What is 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 misinformation strategy to Cp. It is what kept us kidnapped for 60 years on 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.What they are forgetting to tell us is that Cp must be folded properly and have optimal amino acid composition to function fully as an enzyme. The enzyme of choice is ferroxidase, which is the active component of Cp that regulates iron status and iron movement.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. Ferrous Iron (Fe++) Inactivation of Myeloperoxidase (MPO):
   Schultz, J., Rosenthal, S. (1959). “Iron (II) Inactivation of Myeloperosidase.”
   http://www.jbc.org/content/234/9/2486.full.pdf?fbclid=IwAR3a9Ld51OY3p9ycNjR53osXPb0xtYF42oxrb7twiDamra_ATpQSaOUtjTE 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, slowly, to understand what inflammation is. It is 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 yesterday morning:

4. Cp is an Endogenous Inhibitor of Myeloperoxidase (MPO):
   Chapman, A.L.P., et al. (2013). “Ceruloplasmin Is an Endogenous Inhibitor of Myeloperoxidase.”
   http://www.jbc.org/content/288/9/6465.full?fbclid=IwAR28-UrBykhSNZwx97bwAwVaBXpyneUTSPLpkGUAMQZ4fI6pWEd91D_9IUA
   Once again, ceruloplasmin comes to the rescue to regulate, or modulate the myeloperosidase (MPO) response. That is huge! It makes sense that biologically it is 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.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 magnesium, and that sets the stage for an inflammatory response in our heart, which then triggers a rise of MPO. If we were short on ceruloplasmin, the degradation of heme releases more 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:
   Melanson, S.E.F., et al. “Elevation of Myeloperoxidase in Conjunction With Cardiac-Specific Markers After Marathon Running.”
   https://academic.oup.com/ajcp/article/126/6/888/1760076?fbclid=IwAR25YIQcqr_xG1E7NjYyUtZKlR3HWidE6d4jTh9DeYbQJvJjX24aJrHKQ-k

6. MPO >> HOCl- >> heme degradation >> iron release
   Souza, C.E.A., et al. (2011). “Hypochlorous Acid-Induced Heme Degradation from Lactoperoxidase as a Novel Mechanism of Free Iron Release and Tissue Injury in Inflammatory Diseases.”
   https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0027641&type=printable So this has to be among the most boring and academic post, not just on MAG, but on all of FB, wouldn’t you agree?Here’s the punch line:One of my colleagues/clients/fellow iron researcher/friends, Maria Dolores Chagas Oliveira, has helped me see the light on how ceruloplasmin is getting tweaked, and losing its ferroxidase function. It is 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:
   Radi, R. (2003). “Nitric oxide, oxidants, and protein tyrosine nitration.”
   https://www.pnas.org/content/pnas/101/12/4003.full.pdf?fbclid=IwAR1txfZuhFlQWA45ccNH9t8Z9URqnRM48A70UJbl5oo31B4Cnuah1H_TZFA
   What is the best way to nitrate tyrosine?Expose it to superoxide radicals and nitrogen dioxide (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. In my opinion, it is absolutely just the opposite!We come to a full circle. Iron is the stressor! That is causing excess loss of magnesium. We have 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 ironic is that?Have a blessed Xmas Season & New Year’s celebration. I’m going to be keeping a low profile from here until the start of 2016. I have got many consults this week, several clients to catch up with, and will be taking the week between Xmas & New Years off for some much needed R&R…God bless you all. Hope you find this post helpful and informative. Come the New Year, we will be focusing more & more on how to correct this metabolic imbalance that pervades the universe.A votre sante!MORLEY M. ROBBINSFor Facebook Discussion:
   https://www.facebook.com/groups/MagnesiumAdvocacy/permalink/942303632504373/