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The Methylation Pathway Made Easier

 

Screen Shot 2016-04-28 at 11.13.54 AMIt seems to be little more than a modern day catch phrase but methylation is a vitally important process that happens inside each of us.

Whether this pathway is working optimally or is under or over performing can dramatically impact our health and the possible development of an alarming amount of diseases.

Methylation is responsible for many of the most complex and vital processes in the body. The methylation pathways can be found to occur in each cell as well as the liver and the fluid supplying the brain, impacting every system in the body.

Methylation helps determine who we are, what we look like, and how we behave yet even more importantly, it is central to our physical, emotional and mental wellbeing. Without methylation, we could not survive.

 

Vital Functions of Methylation

  1. Methylation of toxic heavy metals, such as mercury and lead, makes them water soluble allowing them to be excreted safely out of the body via urine.
  2. The cells lining our blood vessels must be methylated to repair them. If this process is under functioning (known as under-methylation) cardiovascular disease and hardened arteries can be a detrimental consequence. This condition has been correlated very closely with high homocysteine.
  3. Parts of the DNA in living cells are methylated. In humans, 60% to 90% of the DNA needs to be methylated.
  • Methylation makes embryonic stem cells differentiate irreversibly into different types of body tissue.
  • It suppresses the expression of harmful strands of DNA that have found their way into human DNA over time, such as endogenous retroviruses and mutations.
  • Methylation is very important in neural development and it appears to be essential to long-term memory formation.

4. Abnormal DNA methylation (overmethylation or undermethylation) is associated with the development of cancer; in particular a lower level of white blood cell DNA methylation. In most types of cancer there is over methylation of tumour suppressor genes or  under methylation of oncogenes (cancer-causing genes).

5. Two types of white blood cells (monocytes and lymphocytes) must be methylated. Undermethylation in these cells leads to excessive blood clotting, causing thromboses and strokes. It also leads to impairment of the immune system which is dependent on these white blood cells.

 

 

Why is Methylation so Important?

The methylation pathway is intimately involved in many of our systems including:

  • Nervous System
  • Cardiovascular System
  • Immune System
  • Reproductive System

Is it any wonder that medical scientists and researchers are endeavouring to unravel the secrets of the methylation pathways?

 

Nervous System

Nerve function is highly dependant on proper methylation. We may have all the messengers our body requires yet if the proteins making each nerve’s insulation aren’t methylated,  proper communication between the nerves just isn’t possible.

The breakdown leads to faulty or incomplete nerve transmission that leads many of the symptoms of Autism, (chronic fatigue syndrome (CFS), and multiple sclerosis (MS) as well as physical, emotional, and behavioural changes.

Methylation controls the production and break down of neurotransmitters (NT), which are the chemical messengers in your brain and nervous system. NT’s are simply chemicals that allow brain and body cells to talk to each other. They work in a synchronised fashion so that those in the nervous system are able to communicate with the immune cells, one of the most powerful defences against infection and disease.

Our nervous system must have an efficient communication system in place for sounding the alarm as well as sending messages throughout the body.

 

Cardiovascular System

Methylation is vital for the proper functioning of our cardiovascular system. This pathway mobilises fats and cholesterol, so that they can efficiently be processed and removed from the body without accumulating and clogging blood vessels and attaching to vital organs.

Ultimately, an effective methylation system removes fat and cholesterol that would otherwise lead to heart attacks, strokes, high blood pressure, diabetes, and a newly emerging disorder known as fatty liver disease.

 

Immune System

Methylation also regulates histamine levels, a critical hormone often over-expressed in allergic reactions such as those you may see with seasonal allergies, eczema, asthma, and/or anaphylactic reactions. Histamine reactions range from mild symptoms of sneezing and congestion from animal dander or pollen to life-threatening and even fatal reactions from bee stings or eating simple foods such as peanuts or shellfish.

When optimally functioning, methylation keeps the less wanted genes switched off while it keeps the best genes switched on so that the system runs effectively. This is known as gene expression and cancer and birth defects are examples of where methylation has gone awry.

 

Repair

Methylation also repairs proteins throughout the body, which is critical for optimal function. One such protein, haemoglobin, is an indispensable part of the red blood cell that delivers oxygen throughout the body while carrying waste products back for disposal.

 

Reproductive System

Methylation regulates sex hormone function including oestrogen and testosterone. When one considers that high oestrogen levels may lead to breast cancer whereas low testosterone levels may lead to prostate cancer, we realise that methylation is indeed a vital process.

 

DNA Methylation

DNA Methylation involves attaching work orders to our genetic code in order to gives each cell its’ job description so that one cell is instructed to be a liver cell while another will become a brain cell. This is made possible due to the methylation of RNA, a chemical messenger between cells that is instrumental in individualised cell identity. Methylation influences what goes in and comes out of each cell by making the shell, or cell membrane, more accessible. This allows each cell to fine-tune its needs by adjusting the flow of minerals, such as sodium and potassium, which are also crucial for sending and receiving messages.

Methylation is responsible for making, maintaining, and repairing DNA. If you cannot create and mend what makes you distinctively you, there are going to be serious problems. Methylation regulates the switching on and off of these genes. This is crucial for several reasons, as many of us have more than a few less than desirable variations, particularly cancer causing genes.

 

Undermethylation versus Overmethylation? 

Lets look at histamine – a  critical hormone involved in a number of important functions.

Undermethylation

Undermethylation is associated with low serotonin activity due to histamine not being methylated properly, resulting in an increase of histamine.

When blood contains high levels of histamine, the excess histamine is stored in the blood basophils (a type of white blood cell involved with inflammatory reactions in the body) and brain neurons.

This in turn can result in low levels of neurotransmitters such as serotonin and dopamine – the chemicals responsible for making us feel good. Despite a high energy drive, those suffering from high levels of histamine can often also show symptoms of depression due to low serotonin levels.

People who are under methylators have a genetic tendency to be very low in calcium, magnesium, methionine, and Vitamin B-6 and may have excessive levels of folic acid in nuclei of brain cells.

Overmethylation

Overmethylation conversely causes an overproduction of serotonin, norepinephrine, and dopamine in the brain.  In many cases, high serotonin levels can cause psychological problems including reduced motivation, reduced libido, weight gain, and confusion.

 

Under or over methylation can therefore lead  to:

  • Children with autism have been found to have brain abnormalities which may derive from inadequate methylation of nerve cells during critical stages of brain development in early childhood. Folic acid (in the right form) is essential for methylation and lack of folic acid in pregnant women has long been known to result in brain and spinal abnormalities such as spina bifida. After birth, this methylation process continues to be vital in the development of baby and toddler brains.
  • Developing signs and symptoms of cardiovascular disease such as abnormal blood pressure, enlarged heart, orthostatic intolerance, chest pain or postural orthostatic tachycardia syndrome.
  • Accumulation of abnormal levels of toxic heavy metals
  • Increased susceptibility to a wide range of chronic inflammatory illnesses, including some autoimmune conditions resulting from an inadequate methylation of monocytes and lymphocytes. Understanding methylation provides some insight  in understanding autoimmune and neurological diseases such as multiple sclerosis (MS), seizure disorders, dementia, Lou Gehrig’s, chronic fatigue syndrome (CFS), lupus, fibromyalgia, depression, anxiety, and autism spectrum disorders. So far a definite link has been established between under-methylation of these cells and the development of autoimmune diabetes and Systemic lupus erythematosus (SLE) .
  • Blood which clots more rapidly increasing the risk of  thromboses or strokes.
  • Possible memory impairment and other neurological problems.
  • An increased risk of cancer.
  • A weakened immune system


The Methylation Pathway

So here we go…. (keep in mind that this is extremely simplified)

The body makes different neurotransmitters out of particular amino acids. To do this, it usually changes the amino acid slightly by sticking one or more methyl groups onto the amino acid. This is called Methylation.

A methyl group is one carbon (C) atom with three hydrogen (H) atoms stuck on it. Our body’s can’t make methyl groups out of nothing so it has to have a supply of these methyl groups to work with. The Methylation Cycle is the body’s way of supplying these methyl groups.

Methionine is an amino acid which we get from the protein foods we eat and, once it has undergone methylation, it has given away its methyl group molecules ending up with the totally different amino acid homocysteine.

The primary aim is to have reduced levels of homocysteine and optimal levels of methionine.

 

Step 1

The Methylation Cycle carries methyl groups around the body like cars on a circular track. Being a circle, the pathway could start anywhere. But let’s start where there’s a methyl group attached to a molecule called SAM.

The SAM molecule carries the methyl group to the place where it will be used. 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.

 

Step 2

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.

 

Step 3

The body normally recycles Homocysteine back into SAM via methionine by adding methyl group molecules back onto it; from Step 3 back to point Step 1. 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: Step 1, 2 ,3;  Step 1, 2, 3; Step 1,2,3; 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 substances enable the recycling. They have to be present, or the Homocysteine can’t be changed back into SAM.

 

 

 

The Enzymes Explained

  • MTHFR – stands for Methylenetetrahydrofolate reductase. It converts folic acid to methylfolate (5MTHF)
  • MTR – Methionine Synthase uses methylfolate (folate) and methylcobalamin (B12) to turn homocysteine into methionine
  • MTRR – Methionine Synthase Reductase creates SAM and electrons that make energy in the mitochondria
  • BHMT – The backup system (so to speak) in the liver and kidneys that can also make methionine from choline and TMG
  • CBS – Cystathionine-β-synthase, catalyses the first step of the transsulfuration pathway, from homocysteine to cystathionine. Removes homocysteine from the MTR/MTRR cycle and converts it into cysteine and glutathione
  • AHCY – Adenosylhomocysteinase assists in the conversion of S-adenosylhomocysteine to the compounds adenosine and homocysteine.

 

Diagnosis

If for some reason high homocysteine levels are found this means that somewhere in the recycling half of the methylation cycle some process is not working optimally.

This may be due to:

  • Genetic polymorphisms that reduce the quantity or effectiveness of any enzyme involved in the cycle
  • A deficiency in one or more of the nutrients those enzymes need to do their jobs,
  •  A reduction in gene expression, which could be caused by drugs, infections or other environmental factors.

Emed offers an MTHFR gene test.  The MTHFR gene, technically referred to as Methylenetetrahydrofolate reductase, is a key enzyme required to metabolise homocysteine. Mutations of the MTHFR gene may cause elevated blood levels of homocysteine.

The most common mutation in the MTHFR gene is called C677T. Individuals with two copies of this mutation, i.e. one inherited from their mother and one from their father, are called homozygotes.

This occurs in 5-10% of the population and these individuals are predisposed to developing high blood levels of homocysteine, particularly when their diets are low in folate.

A second mutation in the MTHFR gene, called A1298C, has also been implicated in high blood levels of homocysteine when found in conjunction with the C677T mutation.

Should results come back indicating that there is a genetic polymorphism, Emed recommends having and/or monitoring homocysteine levels as mutations are associated with increased levels of homocysteine. Increased levels of homocysteine in the blood may be associated with an increased risk of heart attacks, strokes, blood clot formation, atherosclerosis, Alzheimer’s disease and other health conditions.

 

Final Word

The Methylation Cycle is a vital and complicated process that has been simplified for the purpose of this article.

That aside it is a process that we should be aware of due to its influence on a number of systems and consequently our health status.

If you are concerned about possible genetic polymorphisms, Emed is equipped to help you determine your MTHFR gene status. Should a genetic abnormality be indicated, our qualified practitioners can guide you with precise supplementation and lifestyle recommendations.

Contact us today for all your enquires.

 

Further Reading 

 

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