Importance of Methylation, genetic defects and how this affects detox

Genetic Basics

In case you are like me and are struggling to remember your high school genetic education I will try and summarize simply!

Each of us have 23 pairs of chromosomes.
One copy of each chromosome is inherited from the female parent and the other from the male parent. Each chromosome has strands of DNA molecules, which contains genetic information. A gene is a section of that DNA.
Therefore we have 2 sets of genes one from our mother and one from our father.

DNA is made of chemical building blocks called nucleotides. These building blocks are made of three parts: a phosphate group, a sugar group and one of four types of nitrogen bases. To form a strand of DNA, nucleotides are linked into chains, with the phosphate and sugar groups alternating.

The four types of nitrogen bases found in nucleotides are: adenine (A), , thymine (T), guanine (G) and cytosine (C). The order, or sequence, of these bases determines what biological instructions are contained in a strand of DNA.

The basis always pair like this due to their unique structure:

Adenine -> Thymine - pairs by 2 hydrogen bonds
Guanine -> Cytosine - pairs by 3 hydrogen bonds

It is these bases that determine which proteins are made (A protein is a chain of amino acid molecules). If you have a genetic defect then your base is replaced by another base and a different protein will be made. Depending on which gene this occurs on will determine what effect this will have.

Importance of Methylation

It is the process your body goes through to donate methyl groups. A methyl group is 1 carbon and 3 Hydrogen.
Well so what and who cares?
Without this your body cannot:

1. Turn on/off genes, prime example is one of those nasty genes that cause cancer
2. Process neurotransmitters (dopamine, serotonin, epinephrine)
3. Process hormones
4. Build immune cells
5. DNA, RNA synthesis
6. Produce energy (CoQ10, Carnitine, ATP)
7. Produce protective coating on nerves - myelination.

Factors affecting methylation by depleting methyl groups:

1. If cofactors such as minerals & vitamins (Especially zinc, magnesium, B6) are not in balance enzymes are not activated and cannot complete methylation. 
2. Taking too much niacin can deplete methyl groups
3. Heavy metals (mercury etc), alcohol, candida, arsenic (found in supermarket chickens, water) and use up methyl groups.
4. Genetic mutations

Why are you talking about this on a blog for mercury poisoning?

Mercury adversely affects methylation. If you do not have good methylation your immune system will be weak (leading to long term chronic infections) and detox will be inhibited.

Testing

You can still order the 23andme test and receive your data. There will be no health interpretaion. It costs about $118 with US post (more if international post required). You will then need to run the data through genetic genie or livewello to work out any genetic defects.

You can ask your dr to order it through a lab (spectracell), but you will have to ask for specific test, whereas 23andme will come back a lot of genetic data (some genes 23andme may not test for but you can check this on their website). A MTHFR gene test only will cost approx $150. Then you may have to pay for others to be done.

Key Genes to be tested

Guidance	GENE		Purpose
Test & treat first	MTHFR	A1298C	Methylation
		C677T	Methylation
If more improvement needed test these	COMT		Neurotransmitters
	MAO A		Neurotransmitters
	CBS		Homocysteine
	MTR/MTRR		Recylces B12
	GSTM1		Major detoxification gene
	SOD		Major detoxification gene
	GAD		Glutomate to GABA
	HNMT		Processes histamine
	QDPR		recyles BH4
	NOS		Processes ammonia, forms nitric acid from arginine
	SUOX		processes sulfites / sulpher and mutation made worse if CBS upregulated

What does MTHFR C677T defect really mean?

The basics of MTHFR C677T: Individuals with the MTHFR C677T homozygous single nucleotide polymorphism (SNP) in their DNA will have a *crippled* MTHFR enzyme of significantly reduced working capacity resulting in lack of production of a very essential human nutrient called L-5-methyl-folate. Since the body fails to produce this crucial nutrient in adequate amounts, supplementation is absolutely critical to longstanding health. Without supplementation, an essential multi-step metabolic process cannot be fully completed which in turn results in numerous additional important nutrients that cannot be manufactured adequately by the body.

The enzyme DHFR (dihydrofolate reductase) is necessary to convert folate into a form usable by the methylation cycle. It is slow and easily saturated, meaning that a high dose of folic acid will sit there waiting in line to be processed (as it is filtered out by the kidneys). It will hinder the function of folate transporters and elevated levels can interfere with white blood cell function. Methyl-folate bypasses this step downstream, providing the nutrient which is used directly (after absorption and transport to cells) by Methionine Synthase (MTR) to feed into the methylation cycle to produce SAMe which is the primary goal of the cycle.

The upshot is that failure to treat MTHFR C677T can result in the development of *multiple* biochemical deficiencies in human cellular biology, decreased ability to detoxify environmental chemical exposures, increased risk of cancers & cancer aggressiveness, & reduced ability to properly maintain healthy DNA replication & cellular health.

Treatment by supplementation with methyl-folate for most people with the MTHFR C677T SNP is simple & effective. Reducing exposure to toxins, consuming a healthy diet & exercise all help to improve cellular & organ health for those with this condition. Other human polymorphisms such as MTHFR A1298C which can be discovered through genetic testing such as 23andme.com can impact MTHFR and should be addressed when possible, also.

MTHFR C677T is one of the most studied & well documented areas of human cellular biochemistry to date but is not yet taught in most medical schools. Therefore, it should be understood that most physicians will not yet have any knowledge of it.

Sources:

http://www.dummies.com/how-to/content/genetics-for-dummies-cheat-sheet.html

http://en.wikipedia.org/wiki/Introduction_to_genetics

http://www.genome.gov/25520880

http://mthfr.net/

https://www.youtube.com/watch?v=QRHif2aVPvw