METHYLATION

Methylation

How to determine methylation status in the body?

Methylation or methylation is an organic chemical reaction in which a methyl group (CH3) is added to a molecule. In biological processes, this is an enzyme-dependent process. The methylation is sensitive to influences from the environment and becomes less efficient with aging. Disruptions in methylation are the basis of a large number of age-related disorders. 

WHY  A METHYLATION PANEL?

Important for a good function of the body are the methylation processes of DNA (the genes), proteins (proteins) and phospholipids.
For example, the expression of genes is influenced by, among other things, the methylation of DNA.
DNA methylation in particular causes the suppression of the expression of (harmful) genes. But also stimulation of genes is possible. Diseases associated with a disorder in DNA methylation include Down's disease, neural tube defect, recurrent miscarriage, arteriosclerosis and cancer.

An example of methylation of a protein is the methylation of myelin. Myelin surrounds the nerves and is important for proper transmission of the nerve signals. When the methylation is disrupted, for example as a result of a vitamin B12 deficiency, the myelin sheath is no longer repaired and degraded. Degradation of the myelin sheath results in neuropathy followed by coordination disorders (ataxia) and paralysis. Disruption of the methylation of proteins has also been linked to various other conditions, such as cardiovascular disease and autoimmune diseases, including multiple sclerosis (MS).
Pospholipids can be found in cell membranes, among others. The methylation of phospholipids contributes to the flexibility / fluidity of the cell membranes. A good structure of the cell membrane is necessary for cell functions, including those related to immunity and to prevent nerve damage. An impaired methylation of phospholipids has been associated with, among others, Alzheimer's disease, Multiple Sclerosis (MS) and Amyotrophic Lateral Sclerosis (ALS). Histamine and Dopamine play a role in this process.


In the methylation process two cycles are important, namely the so-called SAM cycle and the Folic acid cycle (see figure below).

The SAM cycle: In this cycle, a methyl group is linked to homocysteine by means of vitamin B12, thereby forming methionine. Methionine is required for the formation of S-adenosyl methionine (SAM). SAM is the only methyl donor for numerous reactions. After release of the methyl group, SAM is converted to S-adenosyl homocysteine (SAH). This can then be hydrolyzed to homocysteine and adenosine. This hydrolysis reaction is reversible (reversible), but the balance is on the SAH side. As the amount of homocysteine increases, an attempt is made to restore balance by converting it to SAH. SAH is a strong inhibitor of all methylation reactions and competes with SAM for the enzyme methyltransferrase. A decrease in the SAM: SAH ratio reduces the activity of the methyltransferase dependent on SAM.

The folic acid cycle: this cycle is needed to close the SAM cycle and keep methionine available for the formation of SAM. Homcysteine can be remethylated to methionine by the active form of folic acid, methyl-tetrahydrofolate (CH3-THF)
In addition, the following folic acid metabolites play a crucial role in methylation under different physiological conditions: Tetrahydrofolate (THF), 10-formyl Tetrahydrofolate (10-formyl-THF) and 5-formyl Tetrahydrofolate (5-formyl-THF).
Disorders that may result from a disturbance in the methylation are:
  • Abnormal immune function
  • Autism
  • CFS
  • Chronic inflammations
  • Diabetes
  • Down
  • Repeated miscarriages
  • Heart and vascular disease
  • Cancer
  • MS
  • Neural tube defects
  • Neurological disorders
  • Problems with cognitive function in Dementia
  • Psychiatric disorders
  • Disturbed balance between Neurotransmitters
  • Alzheimer's diseaseNieuwe alinea
LITERATURE:
1. S.J. James et al, Am J. Clin. Nutr. 2004;80:1611-7
2. J. Pangborn et al, Spring DAN 2004 conference, Washington DC
3. Role of B-Vitamins in biological methylation by Tapan Audhya PhD
Share by: