Cancer Initiation: Selenium as a nutritional support for the single carbon metabolism and dependent pathways

Friday, January 13, 2017

Selenium as a nutritional support for the single carbon metabolism and dependent pathways

 Introduction

 We have mentioned before that DNA methylation is the currency of cellular differentiation. Although specific DNA methyltransferases have been discovered, the process of methylation is actually very complex, and dependent on a network of nutritional enzymes and vitamins. Because a methyl group has 1 carbon and 3 hydrogen atoms, studies of this complex network is sometimes called single carbon metabolism. (SCM)
 Thus then, if there is a weak link in the network of enzymes that supports single carbon metabolism, the result may be the failure to properly duplicate the methylation patterns during duplication of DNA during the S phase of the cell cycle.  Methylation infidelity can lead to either cancer suppressors that are not expressed in the cell, or oncogenes that are inappropriately expressed and lead to a cancerous clone of cells.
  So then, any factor  which disrupts the complex system we call single carbon metabolism  may ultimately lead to cancer, among many other maladies. By factor, we can either include an nutrient or vitamin which is deficient as well as any environmental or dietary toxin that can interact with SCM enzymes.

 Nutrition

  There are many well known dietary supports of the SCM system. Vitamin b12 is important for the proper cycling and maintenance of glutathione.  Glutathione is a protein that is produced in the body, and is often considered the heart of the SCM system.  Pregnancy is the bodies greatest differentiation event, and vitamins that are important for prenatal health are also SCM supporters. Think b12, folate, and biotin.

 Selenium

  One necessary support of this system that gets considerably less press is selenium. That is because selenium deficiency is historically rare. A beautiful review of selenium is provided by Dr. Jeffrey Dach [2]. Because of the emerging "global economy" and the emergence of "agro-business", populations may not be as closely tied to the soil as it used to be. For that reason, it is important to consider selenium as a component of preventative and healthful nutrition.

 Immunity and cancer defense

 As we have previously discussed, the immune system is also closely tied to DNA methylation, and consequently the SCM system. Specifically we have defined wingspans antigens as those markers that are always suppressed in somatic cells, but trigger an immune response against the host cell when they are expressed. We have proposed that this is an additional level of cancer defense. That is, when DNA is not methylated with proper fidelity upon cell division,  these repressed antigens are expressed, and the immune system is activated. This level of cancer of defense has been termed ( by me ) as the rattlesnake hypothesis. The model of the rattlesnake denotes a symmetry  between the fangs ( danger ) and rattle ( warning ) . In the case of cancer  defense , The symmetry is between telomerase ( danger ) and wingspans antigens ( warning ) . As we have discussed, all cancer cell lines must be immortalized, either by expression of telomerase, or an alternate system of mediators which provide the same outcome. ( maintenance of the cells telomeres. )  ( The ALT system )

Summary

 Selenium is an important component of the single carbon metabolism system which is necessary to support proper DNA methylation. Is any component of the SCM system is deficient, the results may be cancer or autoimmunity as a cancer defense against cells that are showing expression of wingspans antigens as a result of SCM disruption.
  

References


[1 ]Speckmann B1, Grune T.
Epigenetic effects of selenium and their implications for health.
Epigenetics. 2015;10(3):179-90. [PubMed]

[2] Dach, Jeffrey, The importance of Selenium, Part One [jeffreydachmd.com]


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