Plutonium Trojan Horse in the Body

Tags

Alzheimers Disease, biologically important metals, breast milk, chromium, Cobalt, copper, iron, manganese, nuclear energy, nuclear power, nuclear waste, nuclear weapons, plutonium, red blood cells, transition metals, transuranic waste, vitamin B-12, WIPP

Plutonium shares some important similarities with biologically important trivalent transition metals, especially iron. This could have importance from a material science point of view, as well.

“Plutonium tricks cells by ‘pretending’ to be iron
By Jared Sagoff July 8, 2011

Plutonium gets taken up by our cells much as iron does,…

Researchers at the U.S. Department of Energy’s Argonne National Laboratory and Northwestern University have identified a new biological pathway by which plutonium finds its way into mammalian cells. The researchers learned that, to get into cells, plutonium acts like a ‘Trojan horse,’ duping a special membrane protein that is typically responsible for taking up iron.

This discovery may help enhance the safety of workers who deal with plutonium, as well as show the way to new ‘bio-inspired’ approaches for separating radioactive elements from other metals in used nuclear fuel.

Because the bodies of mammals have evolved no natural ability to recognize plutonium—the element was first produced in 1941—scientists were curious to know the cellular mechanisms responsible for its retention in the body. The researchers exposed adrenal cells from rats to minute quantities of plutonium to see how the cells accumulated the radioactive material.

Using the high-energy X-rays provided by Argonne’s Advanced Photon Source, the researchers were able to characterize a particular protein known as “transferrin,” which is responsible for bringing iron into cells. Each transferrin is made up of two subunits, known as N and C, that normally bind iron. When another protein—the transferrin receptor—recognizes both the N and C subunits, it admits the molecule to the cell. However, when both the N and C subunits contain plutonium, the transferrin receptor doesn’t recognize the protein and keeps it out.

Contrary to their expectations, the researchers discovered that in one of the mixed states—when an iron-containing N-subunit is combined with a plutonium-containing C-subunit—the resulting hybrid so closely resembles the normal iron protein that the uptake pathway is ‘tricked’ into allowing plutonium to enter the cell.

‘Although the interaction between plutonium and bodily tissues has been studied for a long time, this is the first conclusive identification of a specific pathway that allows for the introduction of plutonium into cells,’ said Mark Jensen, an Argonne chemist who led the research.

… The research was funded by the U.S. Department of Energy’s Office of Science as well as by the National Institutes of Health.” http://www.anl.gov/articles/plutonium-tricks-cells-pretending-be-iron Author manuscript found here: “An iron-dependent and transferrin-mediated cellular uptake pathway for plutonium“, Mark P. Jensen et. al. (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462652/)

From the Jensen et. al. author manuscript: “… Pu is radiotoxic and is strongly retained by organisms1, Pu uptake from an accident, environmental contamination, or a nuclear or radiological attack can pose significant health risks. Plutonium localizes principally in the liver and skeleton in humans where it remains for decades2. It associates in vivo with the iron-containing proteins serum transferrin and ferritin3,4, but despite the danger of plutonium poisoning, the specific molecular-level pathways Pu travels to enter and localize in cells have never been identified2,5…”

Plutonium shares some important similarities with biologically important transition metals, especially iron. “Plutonium is highly redox active with four oxidation states (III, IV, V, and VI) potentially relevant to living organisms, although Pu(IV) has long been considered the most important under physiological conditions.” Pu (IV) is strongly hydrolyzed at physiological pH, and if there are no steric constraints, “Pu4+ tends to form complexes that are about as stable as those of trivalent first row transition metals, notably Fe3+“. The chemical similarities between Iron (Fe) and Plutonium (Pu) “are particularly important to the metal transport protein serum transferrin (Tf). Transferrin functions to strongly bind and carry two Fe3+ ions into cells, but it also binds Pu4+ strongly…” They “found that mammalian cells could acquire Pu through the common Fe uptake pathway of receptor-mediated endocytosis of metallo-transferrins. However, to be taken into the cell by receptor-mediated endocytosis, Pu needed help from Fe.” Plutonium associates in the body with transferrin and ferritin. So, plutonium cannot get into the cell by itself, but it can ride into the cell, on transferrin, along with an iron ion – the so-called “Trojan Horse”. However, it can only fit adequately in one of the two slots available on the transferrin. (“An iron-dependent and transferrin-mediated cellular uptake pathway for plutonium” Mark P. Jensen, Drew Gorman-Lewis, Baikuntha Aryal, Tatjana Paunesku, Stefan Vogt, Paul G. Rickert, Soenke Seifert, Barry Lai, Gayle E. Woloschak, and L. Soderholm http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3462652/pdf/nihms402471.pdf)

In a related study, Atkinson, et. al. 2005, have presented “evidence for a more general pathway for the irradiation of target cells, mediated through the sequestration of heavy-metal radionuclides by the intracellular iron-storage protein ferritin… Since both transferrin and ferritin are capable of sequestering a multitude of other metals, including radioactive heavy metals (8–10)“, they have postulated “that ferritin may be a significant reservoir for radionuclide deposition…” (Atkinson (2005) et. al., “Intracellular sequestration of 223Ra by the iron-storage protein ferritin,” Radiat Res. 2005 Aug;164(2):230-3 See: http://www.ncbi.nlm.nih.gov/pubmed/16038594

“Iron is a biologically important transition metal as it is also vital to life – it is one of the few trace elements needed for organisms to sustain life. It has three main biological roles:
1. Transport oxygen from lungs to cells It is used to bind to enzymes throughout the body, such as in Hemoglobin to transport oxygen throughout the human body in blood.
2. Energy Production Iron is used in the conversation of sugar, fats, and proteins into adenosine triphosphate, ATP.
3. Catalase Production Iron is involved with the production of catalase and this is important because catalase protects the body from free radical damage.
…
Physical Illnesses Associated with Iron[1]
Diabetes
Nervous System Diseases: Parkinson’s disease, Alzheimer’s disease and behavioral abnormalities, including violence, anti-social behavior, ADHD, and autistic characteristics.
Hypertension and Cardiac Conditions
Kidney Problems” http://en.wikibooks.org/wiki/Structural_Biochemistry/Transition_Metals
Some of these diseases could actually be from plutonium mixed with iron, based on the Jensen et. al. study. This could be from chemical and/or radiological poisoning. Uranium, as a heavy metal, is known to damage the kidneys, and believed implicated in diabetes. Plutonium is also a heavy metal:
“There are two aspects to the harmful effects of plutonium: the radioactivity and the heavy metal poison effects. Isotopes and compounds of plutonium are radioactive and accumulate in bone marrow. Contamination by plutonium oxide has resulted from nuclear disasters and radioactive incidents, including military nuclear accidents where nuclear weapons have burned“. http://en.wikipedia.org/wiki/Plutonium

How Plutonium as a Trojan Horse could cause or contribute to Alzheimer’s disease

According to Raven, et. al., 2013, the hippocampus is heavily damaged in Alzheimer’s Disease, whereas the thalamus, is resistant to Alzheimer’s Disease damage. They found that compared with healthy controls, those with Alzheimer’s Disease had increased ferritin iron in the hippocampus, but not in the thalamus. They conclude that hippocampus damage “occurs in conjunction with ferritin iron accumulation“. (Raven EP, et. al., 2013, “Increased iron levels and decreased tissue integrity in hippocampus of Alzheimer’s disease detected in vivo with magnetic resonance imaging,” J Alzheimers Dis. 2013;37(1):127-36, http://www.ncbi.nlm.nih.gov/pubmed/23792695 ) Plutonium attaches to transferrin, in conjunction with iron. Thus, it is found associated with the iron-storage protein ferritin. So, plutonium could be in the brain, along with the iron, irradiating it.

“Does ionizing radiation influence Alzheimer’s disease risk?” Nasrin Begum, et. al. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3483841/
The above Alzheimer’s Disease study focuses on low LET x-ray and gamma-ray exposure, which is considered less dangerous and destructive, than high LET internal alpha radiation, such as plutonium. This is both because high LET alpha is more “destructive per radiation track” and because it stays in the body over time (A time which varies according to radioisotope and the amount of the radioisotope in the outside environment). Low LET gamma-ray exposure can also occur over time either internally, or externally in a contaminated environment, but will be still “less destructive per radiation track” than internal high LET alpha. Low LET Beta radiation is also “less destructive per radiation track” than alpha, but stays in the body over a time period, which varies according to type of radioisotope and according to its presence in the external environment. In other words, if the environment is contaminated the internal radioisotopes will enter into a steady-state condition within the body. Info on BEIR low and high LET radiation was from here: http://www.dep.state.pa.us/brp/radon_division/BEIR%20VII%20Preliminary%20Report.pdf (The document is now gone).

Unfortunately, there are many radionuclides emitted by the nuclear industry and its waste, which can trick the body, including entering the brain: “most caesium compounds are mildly toxic because of chemical similarity of caesium to potassium, allowing the caesium to replace the potassium in the body, causing potassium deficiency.[31] Exposure to large amounts of caesium compounds can cause hyperirritability and spasms,…[2]” http://en.wikipedia.org/wiki/Alkali_metal Potassium is required for nerve function, including brain and heart function: http://www.nlm.nih.gov/medlineplus/ency/article/000479.htm There is even radioactive iron, an activation product from nuclear reactors, though the half-life is comparatively short – 2.7 years, it will still be around for decades. Furthermore, it appears that alpha emitters would be able to activate and re-activate surrounding objects, such as nuclear waste containers: “Neutrons are produced when alpha particles impinge upon any of several low atomic weight isotopes including isotopes of beryllium, carbon and oxygen.” http://en.wikipedia.org/wiki/Neutron_source
Tritium from nuclear reactors and waste binds to form tritiated water, which then can disperse throughout the entire body. The nuclear industry wants us to believe that tritium is safe because it is distributed uniformly! How crazy is that! Related posts for those interested in details: https://miningawareness.wordpress.com/2014/04/10/radioactive-reindeer-chernobyl-guinea-pigs-part-viii-of-a-series/ https://miningawareness.wordpress.com/2014/05/03/radioactive-reindeer-nuclear-guinea-pigs-part-ix-of-a-series/

Some Biologically Important Trivalent First Row Transition Metals, which Plutonium could mimic

Jensen, et. al., 2012, discuss on p. 2 that “In the absence of steric constraints, Pu4+ tends to form complexes that are about as stable as those of trivalent first row transition metals, notably Fe3+”

Manganese: “manganese in human milk is in the trivalent form bound to lactoferrin, the major iron-binding protein.” USEPA (1997) Manganese. Washington, DC, United States Environmental Protection Agency, Integrated Risk Information System (IRIS). http://www.epa.gov/iris/subst/0373.htm. (See more on manganese at bottom of this post).

Although we couldn’t find an abstract, the title is telling: “Transfer of plutonium from milk into cheese.” Miller CL, Payne JG Jr, Bretthauer EW, Moghissi AA, Health Phys. 1972 Jun;22(6):563-5.

Copper has a diverse role in the body, including for connective tissue and bone repair, the immune system, the reproductive system, and the nervous system.

One example of biological use of Cu3+ is Hemocyanin:
“Hemocyanin is an excellent example of the use in proteins. Hemocyanin is an alternative O2 transport protein that involves the binding of O2 to the two Cu2+, which is then oxidized to Cu3+ after binding. It is different from Hemoglobin in that in doesn’t ‘tag along’ with red blood cells, but is contained in hemolymph.” http://en.wikibooks.org/wiki/Structural_Biochemistry/Transition_Metals

However, Cu3+ may be more important to the human body than often thought: “Copper peptide complexes, with low reduction potentials and high stability in aqueous solution, are of special interest in biological redox processes1 due to the probable participation of Cu(III) in the activity of some enzymes and as an intermediate in the enzymatic DNA cleavage mediated by metalloproteins.” (“Oxidative DNA damage induced by S(IV) in the presence of Cu(II) and Cu(I) complexes“, by María V. AlipázagaI; Giselle CerchiaroII; Horácio D. MoyaIII; Nina CoichevI, J. Braz. Chem. Soc. vol.20 no.7 São Paulo 2009 (http://www.scielo.br/pdf/jbchs/v20n7/a15v20n7.pdf)

Cobalt is at the center of vitamin B12. Whether or not plutonium mimics cobalt, Radioactive “Cobalt-60 can also be released to the environment through leaks or spills at nuclear power plants, and in solid waste originating from nuclear power plants. Nuclear Regulatory Commission regulations allow small amounts of cobalt-60 to be released into the air, or poured down drains as part of a liquid.” http://www.epa.gov/radiation/radionuclides/cobalt.html (The NRC encourages dilution, so it is not “small amounts” but rather diluted amounts.)

“Cobalt [3] [4]
Cobalt is at the core of B12 vitamins.The structure of this is based on the corrin ring. It is used to treat anemia because it stimulates the production of erythropoietin which makes red blood cells… We mainly obtain it from the environment by breathing air, drinking water, and eating food that contain cobalt such as meats, dairy, and leafy green vegetables.

Radioactive cobalt can also cause health concerns. This type of radiation is sometimes used to treat cancer patients. Exposure affects include hair loss, diarrhea,and vomiting.

There are several enzymes that contain cobalt and use it as a ligand to bind to methyls and adenosyl. It is thought that cobalt acts by inhibition of enzymes involved in oxidative metabolism and that the response is the result of tissue hypoxia. More specifically, cobalt blocks the conversion of pyruvate to acetyl coenzyme A (coA) and of α-ketoglutarate to succinate [1].” http://en.wikibooks.org/wiki/Structural_Biochemistry/Transition_Metals

Chromium is a transition metal which can occur in a +3, Trivalent, State

“Trivalent chromium (Cr(III)) ion is possibly required in trace amounts for sugar and lipid metabolism, although the issue remains in debate.[4]” http://en.wikipedia.org/wiki/Chromium

“Chromium [5]

In mammals, chromium, a micronutrient, is only required in small quantities in biological systems. While the exact roles that chromium plays in the body is still unknown, research has proposed that chromium helps maintain proper carbohydrate and lipid metabolism. In the late 1950s. Schwarz and Mertz showed the importance of chromium through experiments involving the diets of rats. When the rats were fed with Torula yeast, a diet lacking chromium, the rats were unable to efficiently remove glucose from the bloodstream. Then when the rats were fed with food rich in chromium, the rats were able to maintain a normal glucose level. This experiment became evidence that chromium depends on insulin.

In the 1980s, Wada and Yamamoto were able to isolate the oligopeptide that binds chromium. This peptide is called chromodulin. Chromodulin is a small molecule of about 1500 Da and can bind four equivalents of chromium ions. The most significant characteristic of chromodulin is its ability of effect insulin by conversion of glucose into carbon dioxide or lipid.

In addition, there has also been some studies that suggests chromium and chromodulin play a role in signal transduction. Analysis of how chromodulin activate or inhibit phosphatase and kinase activity in rat adipocytes reveal an effect of small activation of a membrane phosphotyrosin phosphatase and a significant stimulation of insulin receptor tyrosine kinase activity.” http://en.wikibooks.org/wiki/Structural_Biochemistry/Transition_Metals

Additional information on
“Manganese [6]

The human body averagely contains about 10 to 20 milligrams of manganese mostly concentrated in the pancreas, bone, liver, and kidneys. Manganese plays a role as a cofactor to important enzymes in the mitochondria and in the synthesis of glycoproteins. It can also act as a catalyst in enzyme processes involved in the synthesis of fatty acids and cholesterol. In skeletal and connective tissue development, manganese is involved in the process of mucopolysaccharide synthesis which is important in skeletal and cartilage structural matrix. Lack of manganese can lead to formation of abnormal cartilage and skeletal tissue, impaired connective tissue, poor muscle coordination,and impaired glucose tolerance and management of blood sugar levels. In the liver, manganese helps enzymes convert arginine to urea. In addition, manganese accompanies the enzyme pyruvate carboxylase which converts various non-carbohydrate substances into glucose for later use.” http://en.wikibooks.org/wiki/Structural_Biochemistry/Transition_Metals More: http://en.wikipedia.org/wiki/Manganese

“Metal Homeostasis

Transition metals such as zinc, iron, and copper are relatively essential constituents in the sphere of protein structural stability and functionality. Despite the importance of these metals in biological functions, an overabundance or a deficit of any may issue an action that is harmful to cell growth and viability. As a result, organisms must stabilize metal levels through a homeostatic mechanism. To do this, genes that encrypt the transportation of metals and storage of proteins are often regulated at the transcriptional level when there exist a change in metal concentration.

Many studies have exposed that a bad alteration in zinc, iron, and copper can affect various cancers and diseases like Alzheimer’s and Parkinson’s. This leads to opportunities where metal levels might invite more complex diseases in the future. Therefore, it is crucial to develop an inclusive understanding of how metal homeostasis can uncover possibilities that are health-sustaining and potentially health-risky.” http://en.wikibooks.org/wiki/Structural_Biochemistry/Transition_Metals

As noted above, there can be too much of a good thing. Striking a good balance in vitamins and minerals is already a challenge, without the radionuclide Trojan Horses. What to do as our world food and water supply is increasingly contaminated with these deadly radionuclides? Many governments still give the knee-jerk response from 70 plus years ago that one is unlikely to meet these radionuclides in the environment. This is patently false, especially, where there are nuclear reactors or were nuclear weapons tests. Even in Africa there were nuclear weapons tests and are nuclear reactors. There are nuclear reactors in Latin America. There seems to be no clean zone, only contaminated and more contaminated zones.

Time to shut down and contain the nuclear Trojan Horses before it is too late!

(NB: Emphasis has been added throughout the post).