January 24, 2013

Homocysteine, Methylation and DNA:


In our last Blog update we discussed how high blood homocysteine levels show that 'methylation' reactions are impaired. This has implications for the survival of nerve cells.

Islands in DNA:

Methylation is important for the maintenance of your DNA.  The expression of genes is partly controlled by methylation of short stretches of DNA called 'CpG islands.'  If methylation is impaired, some strands of DNA are far more prone to breaking.  It is thought that homocysteine itself can also cause DNA breakages in neurones (J.Neurosci. 2000;20:6920-26).

Repairing the damage:

Of course, your cells are able to repair DNA. But occasionally mistakes are made; a chemical called 'uracil' can be included in error.  

Uracil has to be removed from DNA, generating yet more temporary breaks.  An enzyme called PARP recognizes damaged DNA and gets it ready for repair.  But in cells with too much DNA damage, such as occurs with impaired methylation, PARP triggers a cascade of events leading to cell death.

This PARP-controlled cell death is the major death pathway for nerve cells, particularly in response to conditions like brain injury, Parkinson’s disease, and stroke.

This is just one pathway linking high homocysteine to death of nerve cells in your brain.

In our next update we will look at other harmful cascades triggered by high homocysteine levels.



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