Compilation of data

COMT/TXNRD2 Catechol-O-methyltransferase, COMT rs769224 (aka, -61 P199P), rs2239393 (aka, A 26166G), rs6269 (aka, A-1324G), rs933271 (aka, A2953G), rs174675 (aka, A309G), rs1544325 (aka, A7406G), rs4646316 (aka, C27870T), rs174696 (aka, C28914T), rs174699, (aka, C30196T), rs9332377 (aka, C31430T). rs8192488 (aka, C438T), rs165599 (aka, G*522A), rs739368 (aka, G14834A), rs165656 (aka, G24601C), rs165774 (aka, G28299A0, rs4633 (aka, H62H), rs5993883 (aka, T13376G), rs4646312 (aka, T24075C), rs740601 (aka, T26501G), rs4680 (aka, V158M). COMT/TXNRD2 rs737866 (aka, A4251G), rs2020917 (aka, C4622T), rs737865 (aka, T4239C).

The COMT gene codes for an enzyme that breaks down catecholamines

The COMT gene provides instructions for making an enzyme called catechol-O-methyltransferase

Two versions of this enzyme are made from the gene. The longer form, called membrane-bound catechol-O-methyltransferase (MB-COMT), is chiefly produced by nerve cells in the brain.

Other tissues, including the liver, kidneys, and blood, produce a shorter form of the enzyme called soluble catechol-O-methyltransferase (S-COMT)

This form of the enzyme helps control the levels of certain hormones.

In the brain, catechol-O-methyltransferase helps break down certain chemical messengers called neurotransmitters.

These chemicals conduct signals from one nerve cell to another. Catechol-O-methyltransferase is particularly important in an area at the front of the brain called the prefrontal cortex, which organizes and coordinates information from other parts of the brain.

This region is involved with personality, planning, inhibition of behaviours, abstract thinking, emotion, and working (short-term) memory.

To function efficiently, the prefrontal cortex requires signalling by neurotransmitters such as dopamine and norepinephrine. Catechol-O-methyltransferase helps maintain appropriate levels of these neurotransmitters in this part of the brain.

Variations in the COMT gene also may be associated with mental illness in people without 22q11.2 deletion syndrome.

Researchers have looked extensively at the potential connection between changes in the COMT gene and the risk of developing schizophrenia.

Most studies have focused on the effects of a particular common variation (polymorphism) in catechol-O-methyltransferase. This variation alters a single protein building block (amino acid) in the enzyme, replacing the amino acid valine with the amino acid methionine. In the longer form of the enzyme, this variation occurs at position 158 (written as Val158Met).

In the shorter form of the enzyme, it occurs at position 108 (written as Val108Met).

Researchers often shorten this notation to Val108/158Met. The change affects the stability and activity of catechol-O-methyltransferase, which alters the enzyme’s ability to break down neurotransmitters in the prefrontal cortex.

Studies of the Val108/158Met polymorphism in people with schizophrenia have had mixed results.

While most studies report no evidence of heightened risk with either methionine or valine at this position, some studies have found a slightly increased risk of schizophrenia in people with valine at position 108/158. Having valine at this position is associated with differences in thought processes that are common in people with schizophrenia, including problems with working memory, inhibition of behaviour, and attention.

Other changes in the COMT gene may also contribute to these differences. Variations in the COMT gene are among many factors under study to help explain the causes of schizophrenia.

A large number of genetic and lifestyle factors, most of which remain unknown, likely determine the risk of developing this condition.

The Val108/158Met polymorphism has also been associated with other disorders that affect thought (cognition) and emotion.

For example, researchers have studied this variation as a possible risk factor for bipolar disorder, panic disorder, anxiety, obsessive-compulsive disorder (OCD), eating disorders, and attention-deficit/hyperactivity disorder (ADHD).

Studies suggest that these conditions may be related to inefficient processing of information in the prefrontal cortex.

As with schizophrenia, however, many factors play a part in determining the risk of these complex disorders.

https://medlineplus.gov/genetics/gene/comt/ 

(1)

Authors of a Meta-analysis of Violent Behaviour in Schizophrenia in 2012 concluded that those individuals with the Met allele in the COMT gene had a modest elevated risk of violence.  (2)

Catechol-O-methyltransferase is one of several enzymes that degrade catecholamines, catechol estrogens, and various drugs and substances having a catechol structure.

In humans, catechol-O-methyltransferase protein is encoded by the COMT gene. Catechol oxidase is the enzyme that initiates oxidisation in fruit in the presence of oxygen.

That is why fruit browns once it has been cut.

Catechol oxidase are ubiquitous; they’re an extremely common group of enzymes and  they’re commonly found  in fruits & vegetables.

It assists plants to repair when they are damaged, as the enzyme converts to another substance (ortho-quinone) that acts as an antiseptic and helps fight bacteria and fungus.

Catechol-O-methyltransferase (COMT; EC 2.1. 1.6) is one of several enzymes that degrade catecholamines (neurotransmitters such as dopamine, epinephrine, and norepinephrine), catechol estrogens, and various drugs and substances having a catechol structure.

COMT is an enzyme that facilitates the degradation of active dopamine in the synapse and is expressed in the pyramidal neurons of the prefrontal cortex and hippocampus (Papaleo et al., 2008).

The COMT gene provides instructions for making an enzyme called catechol-O-methyltransferase

Two versions of this enzyme are made from the gene. The longer form, called membrane-bound catechol-O-methyltransferase (MB-COMT), is chiefly produced by nerve cells in the brain.

Because COMT is a methylation gene, it’s essential to get adequate B vitamins to support COMT, especially B2, B6, B9, and B12 as well as magnesium.

To support COMT methylation, others suggest people with COMT Met/Met also take SAMe.

Always consult a  professional prior to commencing health supplements

There is a safe procedure to restoration of our health

Attempting to self diagnose and self treat may result in a worsening of symptoms or a reaction known as Herxheimers’

Genetic variations in catechol-O-methyltransferase (COMT), an enzyme that degrades catecholamines (e.g., norepinephrine, epinephrine, dopamine and catechol estrogens), dysregulates sympathetic function and increases fatigue.

The COMT gene is also essential in methylation

This is a biochemical process where atoms are transferred from one substance to another

It helps manage or contribute to several vital processes including:

• Inflammation

• Neurotransmitter synthesis

• Cardiovascular function

• Detoxification of certain chemicals and substances

• Energy production

• The expression of DNA and certain genes

• Immune function

(3)

The expression of DNA and certain genes Immune function Between 20 and 30 percent of Caucasians with European ancestry have a COMT mutation. This mutation limits the body’s ability to break down and remove neurotransmitters (NTs) by 3-4 times. These NTs are responsible for planning, behavioural inhibitions, short-term memory, and stress reactions. This will result in difficulty of your body to cope with high levels of circulating neurotransmitters during stressful periods.

Neurotransmitters may also remain higher for longer periods of time extending the stress response, there COMT genes may be a determinant of

• Your stress levels

• How you respond to both negative and positive emotions How you react to stress.

• Your stress resiliency

A loss of one copy of the COMT gene in each cell leads to abnormal regulation of catechol-O-methyltransferase levels in the brain.

Researchers believe that changes involving this enzyme in the prefrontal cortex may help explain the increased risk of behavioural problems and mental illness associated with 22q11 (4)

In Met carriers, more childhood trauma was associated with decreased hippocampal activation, whereas in the Val/Val group childhood trauma was related to increased hippocampal activation.

A loss of one copy of the COMT gene in each cell leads to abnormal regulation of catechol-O-methyltransferase levels in the brain.

https://medlineplus.gov/genetics/gene/comt/

According to Dr Lam, the COMT gene is also essential in methylation. This is a biochemical process where atoms are transferred from one substance to another. It helps manage or contribute to several vital processes including:

Inflammation

Neurotransmitter synthesis

Cardiovascular function

Detoxification of certain chemicals and substances

Energy production

The expression of DNA and certain genes

Individuals with the slow COMT enzyme have higher and faster alpha wave frequency during wakefulness, REM and NREM sleep, which is thought to come from higher levels of dopamine.

https://www.toolboxgenomics.com

People with chronic fatigue tend to have higher catecholamine levels

Specific gene variants can reduce COMT activity. They have been associated with chronic fatigue of multiple origins.

Genetic variations in catechol-O-methyltransferase (COMT), an enzyme that degrades catecholamines (e.g., norepinephrine, epinephrine, dopamine and catechol estrogens), dysregulates sympathetic function and increases fatigue.

It has been suggested that if you have a difficult time methylating because of COMT (or other genes like MTHFR) you might benefit by  limiting strenuous exercise. (3)

Fasting can increase catechols, which can bog down COMT.

So eating regularly and maintaining blood sugar is essential.

https://www.psychologytoday.com/

A loss of one copy of the COMT gene in each cell leads to abnormal regulation of catechol-O-methyltransferase levels in the brain

https://medlineplus.gov/genetics/gene/comt/

Researchers believe that changes involving this enzyme in the prefrontal cortex may help explain the increased risk of behavioural problems and mental illness associated with 22q11.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3862513

The COMT gene provides instructions for making an enzyme called catechol-O-methyltransferase.

An estimated 20-30% of Caucasians of European ancestry have a COMT gene variation which limits the body’s ability to remove catechols (a specific type of molecule that includes dopamine, norepinephrine, estrogen, etc.) by 3-4 times.

This “slow” variation of the COMT gene is called Met/Met, AA, or +/+. COMT is also associated with greater levels of cortisol and HPA axis dysfunction (which is largely responsible for the body’s ability to calm itself and de-stress).

COMT is a methylation gene, and as such it  is essential to get adequate B vitamins to support COMT, especially B2, B6, B9, and B12 as well as magnesium.

To support COMT methylation, others suggest people with COMT Met/Met also take SAMatechol-O-methyltransferase

(COMT; EC 2.1. 1.6) is one of several enzymes that degrade catecholamines (neurotransmitters such as dopamine, epinephrine, and norepinephrine), catechol oestrogens, and various drugs and substances having a catechol structure.

The COMT gene provides instructions for making an enzyme called catechol-O-methyltransferase.

Two versions of this enzyme are made from the gene. The longer form, called membrane-bound catechol-O-methyltransferase (MB-COMT), is chiefly produced by nerve cells in the brain.

catechol-O-methyltransferase is one of several enzymes that degrade catecholamines, catechol estrogens, and various drugs and substances having a catechol structure.

In humans, catechol-O-methyltransferase protein is encoded by the COMT gene.

Catechol-O-methyltransferase is encoded by COMT and is one of several enzymes that degrade catecholamines such as

dopamine, epinephrine, and norepinephrine.

Catechol-O-methyltransferase also plays a role in oestrogen breakdown.

NOTE: Recall that GABA may be called into action to keep high dopamine levels in check. As a result, GABA levels may be low in those with

COMT V158M/H62H homozygous SNPs.

GABA is our calming neurotransmitter

The sympathetic nervous system may dominate over parasympathetic nervous system in those with COMT V158M/H62H homozygous SNPs, so stress management techniques (e.g., life style and dietary changes to remove extraneous inflammatory influences, jettisoning toxic relationships, Heart Math techniques, yoga, etc.) are helpful.

Adrenal support (e.g., glandulars, vitamin B-5 and vitamin B-6, adpatogens, etc.) may also be key to reversing effects of stress/sympathetic nervous system tendency conferred by long-term, poor catecholamine breakdown due to COMT V158M/H62H homozygous SNPs. (5)

According to Dr Wilson, COMT, an RNA copying error, affects catechol methyltransferase.

This is one of several enzymes that degrades catecholamines such as dopamine, epinephrine, and norepinephrine.

As a result, a problem with this imbalance can cause a varying degree of irritability, agitation, anxiety and other symptoms associated with a high level of catecholamines.

In most cases, CBS and COMT problems are not usually DNA defects.

They are best described as a mild genetic variants or weak expressions of certain genes.

They are problems with RNA and protein synthesis, which is highly dependent upon proper nutrition and can be ruined by toxic metals. (6)

DNA replication errors are a powerful source of human disease.

The mutations that are generated by these errors give rise to mutant proteins that drive the pathology of countless genetic diseases.

Mutant proteins can also be generated by errors that occur during other processes though, including transcription and translation.

Problems with mRNA, known as transcription errors occur from at least two templates that allow errors to occur repeatedly at the same position: templates that are naturally error prone, and templates that are artificially error prone due to DNA damage.

Several lines of evidence now demonstrate  that transcription errors are not always random or temporary, and that they can have lasting consequences for human health.

Observations of transcriptions errors have found that they have occurred repeatedly at the same position, and as a result, have produced a continuous stream of a single, mutated protein, thus, effectively mimicking a mutation.

There at least two templates known that occur at the same position, being templates that are artificially error prone due to damaged or defective DNA, or templates that are naturally error prone.

This demonstrates that DNA damage is not necessarily converted into a mutation to produce a mutant, or defective protein, as the damage itself is enough to be sufficient.

Also Reactive Oxygen Species (ROS) are an ample source of DNA damage that results in transcription errors and live for an extended amount of time, accumulating damage to the genome easily.

Additionally, post mitotic cells (mitotic cell division is the formation of new cells that have the identical nature of genetic material in them) are known to possess limited DNA repair capacity, which promotes further damage persistence.

It has been found that transient transcription errors compromise cellular health without the need to mimic mutations.

Even a single errant transcription is capable of altering the fate of a cell. It has been noted in bacteria studies that errors that open up a membrane channel, to allow molecules to enter the cell that stimulate additional channels to open.

The consequence of this results in amplification of cellular activity that allows heritable changes in the physiology of the cell and all its progeny. (7)

As the central dogma of molecular biology, genetic information flows from DNA through transcription into RNA followed by translation of the message into protein by transfer RNAs (tRNAs).

However, mRNA translation is not always perfect, and errors in the amino acid composition may occur.

Mistranslation is generally well tolerated, but once it reaches superphysiological levels, it can give rise to a plethora of diseases.

The key causes of mistranslation are errors in translational decoding of the codons in mRNA.

Such errors mainly derive from tRNA misdecoding and misacylation, especially when certain codon-paired tRNA species are missing.

Substantial progress has recently been made with respect to the mechanistic basis of erroneous mRNA decoding as well as the resulting consequences for physiology and pathology. (1) a

 

REFERENCES

1. a Ou X, Cao J, Cheng A, Peppelenbosch MP, Pan Q. Errors in translational decoding: tRNA wobbling or misincorporation? PLoS Genet. 2019;15(3):e1008017-e.

1. Sterling Hill Compiled by Cynthia Smith B, JD, With contributions by Sterling Hill Erdei and Carolyn Ledowsky N. SNPBit Compendium 2019

1. www.drlwilson.com_ARTICLES_FOLIC ACID DEFECTS.
2. Medicine NLo. COMT gene catechol-O-methyltransferase. Medline Plus. 2021.

2. Singh JP, Volavka J, Czobor PCl, Van Dorn RA. A Meta-Analysis of the Val158Met COMT Polymorphism and Violent Behavior in Schizophrenia. 2012.
3. Hoenemeyer TW, Baidwan NK, Hall K, Kaptchuk TJ, Fontaine KR, Mehta TS. An Exploratory Analysis of the Association Between Catechol-O-Methyltransferase and Response to a Randomized Open-Label Placebo Treatment for Cancer-Related Fatigue. Frontiers in psychiatry. 2021;12:684556-.
4. Philip N, Bassett A. Cognitive, behavioural and psychiatric phenotype in 22q11.2 deletion syndrome. Behav Genet. 2011;41(3):403-12.
5. Sterling Hill Compiled by Cynthia Smith B, JD, With contributions by Sterling Hill Erdei and Carolyn Ledowsky N. SNPBit Compendium 2019.
6. Wilson D. www.drlwilson.com_ARTICLES_FOLIC ACID DEFECTS.
7. Anagnostou ME, Chung C, McGann E, Verheijen BM, Kou Y, Chen L, et al. Transcription errors in aging and disease. Translational Medicine of Aging. 2021;5:31-8.

 

DNA vs. RNA – A comparison chart

DNA vs. RNA – A comparison chart (1.a)

Comparison	DNA	RNA
Full Name	Deoxyribonucleic Acid	Ribonucleic Acid
Function	DNA replicates and stores genetic information. It is a blueprint for all genetic information contained within an organism.	RNA converts the genetic information contained within DNA to a format used to build proteins, and then moves it to ribosomal protein factories.
Structure	DNA consists of two strands, arranged in a double helix. These strands are made up of subunits called nucleotides. Each nucleotide contains a phosphate, a 5-carbon sugar molecule and a nitrogenous base.	RNA only has one strand, but like DNA, is made up of nucleotides. RNA strands are shorter than DNA strands. RNA sometimes forms a secondary double helix structure, but only intermittently.
Length	DNA is a much longer polymer than RNA. A chromosome, for example, is a single, long DNA molecule, which would be several centimetres in length when unravelled.	RNA molecules are variable in length, but much shorter than long DNA polymers. A large RNA molecule might only be a few thousand base pairs long.
Sugar	The sugar in DNA is deoxyribose, which contains one less hydroxyl group than RNA’s ribose.	RNA contains ribose sugar molecules, without the hydroxyl modifications of deoxyribose.
Bases	The bases in DNA are Adenine (‘A’), Thymine (‘T’), Guanine (‘G’) and Cytosine (‘C’).	RNA shares Adenine (‘A’), Guanine (‘G’) and Cytosine (‘C’) with DNA, but contains Uracil (‘U’) rather than Thymine.
Base Pairs	Adenine and Thymine pair (A-T) Cytosine and Guanine pair (C-G)	Adenine and Uracil pair (A-U) Cytosine and Guanine pair (C-G)
Location	DNA is found in the nucleus, with a small amount of DNA also present in mitochondria.	RNA forms in the nucleolus, and then moves to specialised regions of the cytoplasm depending on the type of RNA formed.
Reactivity	Due to its deoxyribose sugar, which contains one less oxygen-containing hydroxyl group, DNA is a more stable molecule than RNA, which is useful for a molecule which has the task of keeping genetic information safe.	RNA, containing a ribose sugar, is more reactive than DNA and is not stable in alkaline conditions. RNA’s larger helical grooves mean it is more easily subject to attack by enzymes.
Ultraviolet (UV) Sensitivity	DNA is vulnerable to damage by ultraviolet light.	RNA is more resistant to damage from UV light than DNA.