Methylation

The Methylation Cycle

Explanation of the Methylation Cycle. The body makes different neurotransmitters out of particular amino acids. To do this, it usually changes the amino acid slightly. It does this mostly by sticking one or more methyl groups onto the amino acid.

To summarise, methylation is involved in many of our most vital bodily functions, by offering support and/or managing, such processes as:
1) Detoxification
2) Controlling inflammation
3) Maintaining DNA
4) Immune function
5) Energy production
6) Mood balancing

Some of the conditions linked to poor methylation include but not limited to; cardiovascular disease, cancer, diabetes, neurological conditions, autistic spectrum disorders, chronic fatigue syndrome, Alzheimer’s disease, miscarriages, fertility, and problems in pregnancy, allergies, immune system, digestive problems, mood and psychiatric disorders as well as the aging process.

A methyl group is one carbon (C) atom with two hydrogen (H) atoms stuck on it. The result looks a bit like Mickey Mouse -- a big round thing (the face) with two smaller round things (the ears) at the top. The body can't make methyl groups out of nothing. So it has to have a supply of these units to work with. The Methylation Cycle is the body's way of supplying these methyl groups. The diagram below is a simplified view of the Methylation Cycle. Let's see how it works.

From A to B. The Methylation Cycle carries methyl groups around the body like railcars on a circular track. Because the track goes around in a circle, we could start anywhere. But let's start at the bottom, at point A. There a methyl group is attached to a molecule called SAM. The SAM molecule carries the methyl group to the place where it will be used -- point B. When it gets there methylation happens. Methylation is just a word meaning that the methyl group is popped off the SAM molecule and stuck on an amino acid to make a neurotransmitter.

From B to C. What happens to the SAM molecule when the methyl group is taken off? When the methyl group is gone, the molecule is not SAM anymore. It turns into a different molecule called Homocysteine. Now we've moved from point A all the way to point C.

From C back to A. Here's where things get tricky. The body normally recycles Homocysteine back into SAM -- from point Cback to point A. A new methyl group is added to turn the molecule back into SAM again. Then the cycle is complete. The molecule goes round and round -- A-B-C-A-B-C-A-B-C, etc -- carrying methyl groups where they are needed. That's why we call it a Cycle. But that can happen only if there's enough of certain vitamins and nutrients around -- vitamin B12, folic acid, and a nutrient called TMG. These things enable the recycling. They have to be present, or the Homocycteine can't be changed back into SAM.

A depressing shortage. So what happens if the required nutrients just aren't there? Look at the diagram to the right. The Homocysteine doesn't get recycled. Instead, it simply piles up at point C unchanged. Big dollops of it accumulate. Because Homocycteine isn't being changed back into SAM, a shortage of SAM soon develops. And when there is a shortage of SAM, not as many neurotransmitters are made. So soon there is a shortage of neurotransmitters, too. The shortage includes Serotonin and Norepinephrine, those anti-depression neurotransmitters. A "chemical imbalance" -- the very kind the antidepressant ads talk about -- has appeared. The individual gets depressed.

Insight! Now we see why deficiencies of specific vitamins and minerals can lead to depression. The shortages tied to depression are of the very nutrients required to keep SAM circulating. When they aren't there, the SAM dries up. That's why supplementing with those vitamins and minerals can help with depression.

Why SAMe works. Understanding the Methylation Cycle also helps us understand why the supplement SAMe can help relieve depression.

SAMe is a special form of SAM designed to be taken orally. Taking SAMe increases the available supply of SAM in the body. That leads to increased methylation, and so to increased production of neurotransmitters. It quickly revs up the methylation process to bring neurotransmitter production back up. That can quickly relieve depression.

SAMe doesn't help with recycling Homocysteine, though. That substance continues to build up. Even so, supplementing with SAMe can provide a band-aid solution. It can power up methylation until something can be done to bring Homocysteine recycling back to normal.

References.

http://www.news-medical.net/life-sciences/What-is-DNA-Methylation.aspx

http://www.sabiosciences.com/pathwaymagazine/pathways8/epigenetic-modifications-regulate-gene-expression.php

https://www.ncbi.nlm.nih.gov/pubmed/11343896

http://onlinelibrary.wiley.com/doi/10.1576/toag.12.1.037.27556/pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107542/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3174260/

https://www.ncbi.nlm.nih.gov/pubmed/18407786

http://science.sciencemag.org/content/293/5532/1068

https://www.ncbi.nlm.nih.gov/pubmed/15705854

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4422757/

https://www.ncbi.nlm.nih.gov/pubmed/23359152