COMT and VDR Genes and DOPAMINE and NOREPINEPHERINE…and people sensitive to methyl donors.
Those with the Vitamin D Receptor Taq [VDR Taq (+/+)] mutations do not make Dopamine and therefore Norepinepherine very well.
Those with the Catechol-O-Methyl Transferase [COMT +/+] mutations cannot break down Dopamine and Norepinephrine very well.
A normal VDR [-/-] and the abnormal COMT [+/+] enzyme essentially aggravate the situation so that the concentration of Dopamine may be increased.
When the person has a perfect VDR taq [-/-] and they have the COMT [+/+] mutations then:
The good working VDR taq [-/-] allows them to make plenty of Dopamine.
The lousy COMT [+/+] causes ... ..more
*Circulatory & blood clotting factors
*DNA synthesis & repair via thymidine synthesis
*Gene expression via epigenetic regulations such as histone modification
*Nitric oxide synthesis, aka blood vessel elasticity
*Removal of homocysteine, a potentially toxic and atherogenic amino acid
*Synthesis of powerhouse antioxidants such as Glutathione & SOD
*Neurotransmitter synthesis & degradation - dopamine, serotonin, norepinephrine, glutamate, GABA
*Biotransformation (aka “metabolism & detoxification”) of chemicals, carcinogens & drugs
*Synthesis of immune cells
*B-12 & Folate utilization
*Organ, tissue and fetal development
While their program is expensive it does seem like it would really make one a kind of expert.
Now if I could just find common, insured tests for ... ..more
I found this excellent description in Amy Yasko's forum: ch3nutrigenomics.com. It was posted by one of the members on the site- raji: http://www.ch3nutrigenomics...
This is a private blog, but it is a very rich source of information about methylation, nutrigenomics and dietary supplementation
Here is a copy of the post:
Methyl group: A methyl group is simply a single carbon atom bonded to 3 hydrogen atoms (CH3).
Methylation: Transfer of methyl groups from one chemical to another is called methylation. Essentially any chemical compound that has a methyl group as part of its chemical ... ..more
#Epinephrine is one of the “Fight or Flight” #Hormones This NT is derived from #norepinephrine & released by the #adrenals. Hence, it is also known as #adrenaline . Epinephrine is also essential in #metabolism and regulates attention and mental focus & clarity as well as arousal (alertness & waking up), and thinking. It also inhibits #insulin release and raises the amount of fatty acids in the blood; both of which you’ll require for fuel. This very neurotransmitter induced anxiety and heart racing the moment you heard the word “ #Methyltetrahydrofolate ” or “ #methylation .” Epinephrine also raises your #bloodpressure and speeds up your heart rate.
High levels have been linked to sleep problems, #anxiety and #ADD or #ADHD. Low levels can result in #fatigue , lack of focus, and difficulty losing weight. ..more
There is little known about the A1298C MTHFR mutation. Or so it seems.
Research seems to ignore it almost completely while the C677T MTHFR mutation gets all the attention and glory.
For those who have the A1298C MTHFR mutation, this is frustrating.
Symptoms exist and doctors are saying there is no correlation between the MTHFR A1298C mutation and your symptoms – right?
I’d like to prove them wrong – at least for the symptoms which do correlate with the A1298C MTHFR mutation.
The MTHFR A1298C mutation may affect you if you are either:
--Homozygous A1298C MTHFR mutation
--Compound heterozgous A1298C + C677T ... ..more
The Major Tasks of Methylation
In order to provide a brief overview, the following methylation tasks have been vastly streamlined. In reality, there is an endless array of both direct and indirect Methylation activities within the human body. Even so, this summary should provide greater understanding of this highly complex pathway, as well as the complications that can arise from various defects or toxic exposures.
Methylation is responsible for the following:
1. Nervous system function (brain, spinal cord, & nerve cells). It’s critical for the insulation around nerves (myelin), which allows signals to properly transmit via this sheath, or outer ... ..more
Vitamin D Receptor “Determines donors”
VDR Taq tt = -/- (green, no defect) tolerates fewer methyl donors
VDR Taq TT = +/+ (red, complete defect) tolerates more methyl donors
Partial or complete defects may mean you will not readily absorb Vit D from sun exposure. This may also contribute to seasonal depression, particularly when the sun is at it's lowest in the fall/winter season. Many studies in the past decade have noted a strong correlation between Vitamin D deficiency and neurological degeneration. In fact, aside from having implications in Parkinson’s and dementia, this SNP is highly associated with Multiple Sclerosis ... ..more
Methylenetetrahydrofolate reductase (MTHFR) supports one's health, well-being and detoxification and can be defective in a fairly large percentage of our population. About 45% of Caucasians, 70% of Hispanics and about 30% of southern Italians have a genetic defect.
The MTHFR gene produces the MTHFR enzyme. This enzyme is responsible for the circulating form of folate. Folate is very important in homocysteine regulation. The MTHFR enzyme metabolizes folic acid into 5-MTHF, which is needed to combine with homocysteine to break it down and to facilitate methylation (detoxification) processes in the body. The MTHFR enzyme is essential for the body to ... ..more
It is important to understand the basics of methylation, and although a more detailed study of #methylation chemistry may be interesting, for our needs, it is not really necessary to study it here as it will only serve to confuse matters, so only the most important aspects will be considered.
Put simply, the methylation process makes #neurotransmitters (mood building blocks), and the issue of a person being an under or over methylator can be confusing, because there is contradiction between the various sources of information on the methylation process. For our purposes, we'll say that an over methylator is ... ..more
MAO-A (Monoamine oxidase A) is a critical enzyme involved in breaking down important neurotransmitters such as serotonin, norepinephrine, and dopamine. While a homozygous (+/+) mutation is very common, prolonged periods of stress, violence, or trauma can lead to epigenetic changes that further decrease enzyme activity. On the table above, males only have one allele since the gene is inherited through from their mother since it is located on the X chromosome.
Males are more likely to have this mutation, represented on the table as homozygous (+). Only females can be heterozygous (+/-) for this mutation.
When a (+/+) MAO-A mutation is combined with a ... ..more
CBS (cystathionine beta synthase) catalyzes the first step of the transsulfuration pathway, from homocysteine to cystathionine. Dr. Yasko considers addressing CBS mutations as first priority aside from addressing the gut.
This enzyme converts homocysteine to cystathionine. In a separate reaction, cystathionine is then converted to cysteine which in turn goes to taurine or glutathione among other things.
CBS defects are actually upregulations. This means the enzyme works too fast. Therefore, it is common to see low levels of cystathionine and homocysteine since there is a rapid conversion to taurine. This leads to high levels of taurine and ammonia.
The upregulation ... ..more
#Sympathetic Nervous System “Fight or flight” or “Type A’s”
There are 3 basic #SNS Dominant subtypes: Basic, Extreme, & Inefficient SNS Dominant types. The following is a summary of the average SNS Dominant types.
Personality traits vary widely in this group depending on whether they are more analytical vs. emotional. For instance, more emotionally based SNS Dominants are likely to be more volatile and “nervous” whereas the more analytical type does not.
The sympathetic nervous system (SNS) activates the glands and organs that defend the body against attack, whether it is running from a saber toothed tiger or you are struggling with a dreadful job and difficult boss. It is called the fight or flight system and once activated, it directs more blood to the muscles, #adrenals and the brain yet away from the digestive organs and skin. The adrenals pump out #epinephrine while the sympathetic nerve endings throughout the body release #norepinephrine . This system is #catabolic , which simply means that energy is used to prepare for defense, rather than for nourishment, healing, or waste removal. #Sympathetic activity triggers the thyroid and adrenal glands to provide extra energy for fighting or running away. The heart rate and blood pressure also increase, just as the blood flow to the digestive system and kidneys decreases. This process is largely due to the intensified release of stimulating chemicals, known as #neurotransmitters #epinephrine and #norepinephrine . While this activity is critical for survival, those who have chronic activation of the SNS often develop #anxiety, #insomnia , heart racing or disease (heart failure), and adrenal #fatigue . They also have “goose bumps” more frequently than other types and tend to do best in warmer weather. A Sympathetic Dominant Nervous System often leads to significant gastro-intestinal issues due to the poor #digestion of meats and fats. These folks often feel as though food "sits like a rock in my gut". Due to the rising levels of Norepinephrine (the body’s flight or fight neurotransmitter), digestion shuts down to reserve precious resources for survival. Chronic activation can lead many to feel agitated, jittery, wired, & restless as well as prone to sleep disturbances and anxiety. They may also experience the vicious cycle of the “Wired but tired” sensation when eating an inappropriate diet or taking the wrong supplements, which in their case, is filled with sweets and other junk foods or heavy proteins. When a dysfunctional sympathetic nervous system reigns supreme, one may experience anxiety, stress, or feelings of panic, which should normally only occur in response to a perceived threat. Subsequently, they may overreact to even the mildest of daily troubles.
These individuals often start out thin and active yet poor diets—usually filled with sweets and starchy carbs often lead to later weight gain. When busy or stressed, they frequently forget to eat regularly, if at all. They are often pale, do not tolerate cold weather and tend to have colder hands & feet. Such individuals are often impatient and easily frustrated or angered, yet it appears to quickly pass. They often make for volatile partners and bosses, in that they frequently explode; yet minutes later have already moved on. They are also frequently viewed as “intense,” “aloof,” or “bold,” and have a tendency of “sticking their foot in their mouths” by being too aggressive or forward. Nevertheless, #genetic & environmental factors influence this area considerably.
They are also very driven, ambitious, and motivated people who may excel in academics or in high energy vocations that require multi tasking and social interaction. Many also enjoy a stimulating debate or confrontation (attorneys, politicians, generals). When healthy ... ..more
A chemical made in the BH4 cycle, which is used to produce dopamine and serotonin, neurotransmitters strategic in regulating mood, sleep, attention and focus, reward seeking behavior, addiction, and sense of wellbeing. BH4 is also critical in the urea cycle (waste facility) for cleaning up ammonia and making nitric oxide. A shortage of this important chemical has widespread repercussions.
Tetrahydrobiopterin BH4 Cycle produces the BH4 used for making neuro-talkers (dopamine, epinephrine, nor-epi, serotonin, & melatonin). It cleans up toxic ammonia in The Waste Cycle & makes Nitric oxide to protect the heart & brain.
Though controversy exists regarding this cycle’s function, Dr. Yasko’s theory indicates that The Big Motherflipper (MTHFR A1298C) may drive this cycle in the reverse direction and several independent studies support this finding. This leads to a chemical exchange among BH2 to BH4, a multi-purpose product that is used in both the Waste Facility (urea cycle) and BH4 Industry. Within the Better Health 4 Life Industry, BH4 produces chemicals known as neurotransmitters, or neurotalkers (NTs), including dopamine, serotonin, melatonin, norepinephrine, and epinephrine. NTs are central for the communication between nerves and cells as well as stabilizing the crisis response, mood, and sleep cycles. Chronically low BH4 levels increase the risk for ADD/ADHD, Bipolar Disorder, OCD, insomnia, depression, anxiety, and many other quality of life issues. Think of this company as AT&T with a philanthropic twist since it donates BH4 to the Waste Facility for environmental clean up as well as supporting the community in health & wellbeing.
The Waste Facility uses BH4 to clean up toxic ammonia and generates nitric oxide, an element that keeps blood vessels open and free of plaque. Yet if BH4 is scarce, it cannot clean up waste or deliver vital nutrients to the Power Plant (fumarate) so that noxious chemicals back up into SAM’s Corporation. Given the fact that it takes 2 grains of BH4 to clean up 1 granule of ammonia, as well as 2 of BH4 to create just 1 bit of nitric oxide, its easy to see how problems might arise. This underscores the BH4 Industry’s role throughout the community since unlike an actual factory; it isn’t permitted to shut down for repairs or maintenance.
While there are many factors that may impact this cycle, several are listed below:
1. A ... ..more
Think “nervous, nimble and nightmares” with Nor-epi. This is due to nor-epinephrine’s #adrenalin effects on the body as the main “fight or flight” #neurotransmitter . It’s essential for action in order to ward off attackers and initiate battle or escape. When we encounter something frightening, such as the sound of someone in your house at 3am, your nervous system releases nor-epinephrine. Once tired, you’ll suddenly feel the need to spring into action! Your heart starts to pound and hearing and vision become extremely acute while muscles tighten for attack. Unless you panic, you’ll also have clearer ... ..more
#Histamine is most commonly known for it's role in #allergic reactions but it is also involved in other neurological functions and can affect your #emotions as well as behavior. Histamine helps control the #sleep -wake cycle and promotes the release of epinephrine and #norepinephrine . This may be the explanation for red ears and #flushed cheeks in susceptible children and adults with high histamine levels.
High levels have been linked to obsessive-compulsive ( #OCD ) tendencies, #depression , and #headaches . Low levels can contribute to #paranoia , low #libido , #fatigue , and multiple medication sensitivities.
it is important to consider that those with the #CBS ... ..more
Lithium has been known for years to be useful for #bipolar disorder. Despite all that is known about lithium and its impact on biochemical pathways, no one has defined the mechanism by which lithium has its impact on bipolar disorder. It is likely to be an effect on multiple pathways. There are a number of enzymes in the body that are known to be impacted and inhibited by lithium.
Lithium comes together with methylation at #COMT, the enzyme catechol-o-methyl-transferase. COMT breaks down #dopamine and #norepinephrine. Dopamine is a critical #neurotransmitter for motivation, focus and attention, among other functions ... ..more
#Homocysteine is a toxic waste by-product of protein and amino acid metabolism, and #methylation in the body is going on constantly, converting this damaging homocysteine into the #antioxidant #glutathione.
Methylation also converts homocysteine into an important biochemical called #SAMe , a vital methyl donor for the production of the all important neurotransmitters dopamine, serotonin and their derivatives. This is how the body makes good use of this toxic element.
Keeping homocysteine at a healthy, low level is extremely important for keeping our risk of heart disease, stroke and Alzheimer's disease as low as possible. High levels of homocysteine, if left ... ..more
CBS C699T cystathionine beta synthase AKA The Hole in the Bucket. This Priority # 3 Mutation
Tip! It is crucial to address any gut issues before you thoroughly address the CBS defect. Since chronic gut issues lead to higher bacterial loads, thus leading to higher ammonia production as well as leaky gut (reducing nutrient absorption and increased risk for food sensitivity) this area is paramount. You can begin to address the CBS prior to fully addressing gut issues though they should be done in concert. Since the CBS is one of the most important issues to address, I’ve decided to ... ..more