MTHFR C677T and A1298C…how they don't work correctly By Carol Savage
MTHFR C677T...METHYLATION CYCLE...Epigenetics [SAMe and methylation of our DNA]
The MTHFR C677T snps causes the enzyme to be unable to utilize the cofactor FAD/FADH2 properly. The snp mistake [C677T] causes the enzyme to be temperature labile. As a result, the cofactor FAD disengages and subsequently L-Methyl Folate [5-MTHF] cannot be made. So, MTHFR C677T interferes with the forward action of the MTHFR enzyme and subsequently interferes with the conversion of Homocysteine into Methionine and the making of SAMe.
L-Methyl Folate is most beneficial to ... ..more
MTHFR and L-METHYL FOLATE… Some Basic Information By Carol Savage M.D.
If you have the MTHFR Gene Mutations C677T and or A1298C and are already taking some L-Methyl Folate [5-MTHF] and Vitamin B12 you might also consider the following:
FOOD Eat plenty of Green Vegetables and beans to get some Dihydrofolate [DHF] and Vitamin B2 [Riboflavin] and many other naturally occurring minerals and vitamins that the body needs etc.
DIHYDROFOLATE [DHF] Dihydrofolate is needed to provide the earlier FOLATE PATHWAYS [the reactions that occur prior to the MTHFR enzyme] with the kinds of folates that they need in order ... ..more
The MTHFR gene provides instructions for making an enzyme called methylenetetrahydrofolate reductase. This enzyme plays a role in processing amino acids, the building blocks of proteins. Methylenetetrahydrofolate reductase is important for a chemical reaction involving forms of the B-vitamin folate (also called folic acid or vitamin B9). Specifically, this enzyme converts 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate. This reaction is required for the multistep process that converts the amino acid homocysteine to another amino acid, methionine. The body uses methionine to make proteins and other important compounds.
How are changes in the MTHFR gene related to health conditions?
homocystinuria - caused by mutations ... ..more
By Helen Janneson Bense
A1298C single nucleotide polymorphism (SNP) affects the enzyme known as 5,10 MethyleneTetraHydroFolate Reductase (MTHFR). This polymorphism involves a down regulation of the MTHFR enzyme, responsible for the backwards reaction of the folate cycle, where 5-methylfolate (5MTHF) is converted into tetrahydrofolate (THF). This reaction is most important for the production of BH4 – tetrahydrobiopterin. Each turn of the folate cycle and conversion of 5MTHF to THF produces 1 molecule of BH4. In heterozygous and homozygous states, enzyme activity will be compromised by
approximately 30% and 70% respectively.
Functions of BH4
Cofactor for all three isotypes of nitric ... ..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
ACAT is Acetyl-Coenzyme A Acetyltransferase [ACAT] [mitochondria]
A block at this point in [ACAT] can lead to increased levels of MMA (Methylmalonic Acid)." ...."MMA may inhibit Succinate CoQ Reductase. The enzyme succinate CoQ Reductase is important in electron transport."
Methylmalonic Acid [MMA] is related to Vitamin B12 biochemistry.
#ACAT is treated with Adenosylcobalmin (for high MMA), bile salts, policosanol, pancreatic enzymes, vitamin K, vitamin E, lactoferrin, nucleotides, and CQ10. ...but which ones, how much and how long you take each of these (if at all) depends on your other mutations as well as biochemical testing. Things you want to monitor ... ..more
ACAT Acetyl-Coenzyme A acetyltransferase AKA A bad Gut & Oxalates issues. This is Priority mutation # 2.
Although this mutation is fairly uncommon, it significantly impacts the Energy Cycle (citric acid cycle) and mitochondrial function. The influences are wide and far ranging and include bile salt production, cholesterol, fatty acids, and the processing of oxalates. Notwithstanding a partial or full defect, many have a “functional” variation due to the impact of aluminum, heavy metals, and toxins as well as other defects that impact this area such as the NOS, MTHFR, & CBS. Upon viewing the methylation community diagram, it is important to note that the energy cycle is closely connected to each sequence, yet it is intimately linked to both the waste cycle and SAM’s Corporation.
Since the energy cycle is essential for processing and converting all dietary nutrients (glucose, fats, proteins) into useable forms of energy, a breakdown anywhere down the line might trip an internal alarm. This is analogous to your car’s “low fuel” gauge. Just as any industry processes coal, gas, or oil for energy production, your body must have the essential nutrients in order to properly function. If you visualize the energy cycle as a clock, each hour represents an area in which one nutrient or substance converts into a more compatible form of energy. Depending on digestive function, diet, rate of absorption, and the presence of any genetic quirks, a problem might occur at any point within the device. This may lead to significant chemical imbalances within your body chemistry as well as mitochondrial dysfunction or disorders.
The ACAT plays a key role in creating bile salts, which is crucial for cholesterol and other membrane lipid balances. While we tend to view cholesterol and other fats as the “bad guys” in the war against disease, these compounds are critical for general health and wellbeing. Whether it’s the coating surrounding a nerve, cell, or organ, cholesterol is essential in its production. Think of your home’s electrical wiring and the thick, plastic or rubber coating normally found protecting it. An exposed wire is vulnerable and may “short out,” so that the impulse isn’t transmitted. Similarly, the body’s nervous system requires the protection afforded from a nice, thick fatty coating or fundamental connections may never be made. An exposed nerve may lead to a misfire, which is often the source behind the early symptoms found in neuroimmune disorders. This often includes signs such as tremors, muscle fasciculations, weakness, and fatigue as well as word groping and poor concentration and retention. Without cholesterol, you also cannot make several vital hormones, including, your sex hormones (estrogen & testosterone) or insulin. Therefore, low cholesterol levels are not as beneficial as one would initially think.
Finally, if a chronically ill person has had heavy aluminum or other toxic exposures along with a partially functioning ACAT, energy production is likely to stall to a near standstill. Moreover, as outlined in the energy cycle, other problems may include:
1. More B-12 depletion, which has ramifications throughout the entire system.
2. Cholesterol & fatty acid imbalances, often leading to toxic fatty acid buildup & high cholesterol.
3. Decreasing bile salts & increased taurine production as well as poor cell wall function since they all rely
on the proper breakdown of cholesterol through the ACAT.
4. Poor breakdown of fats, carbohydrates, & proteins to fuel other cells, nerves, tissue, & organs.
5. Rising oxalate levels that may cause painful urination and bladder & kidney stones.
6. Co Q-10 reduction, which is also necessary for mitochondrial function & energy.
7. Limited energy for the Waste Facility & SAM’s Corp. due to less conversion of methionine to SAMe. In
having over 400 methylation functions, SAMe is critical for the entire community.
As the energy factories of each cell, mitochondrial damage has significant implications. In fact, anything that demands more energy, including the gut and the brain, are particularly vulnerable. Significant blocks may limit the availability of bile salts; hence the digestive process is doubly burdened. This provides a valid reason for many unexplained digestive problems, while explaining poor growth & development as well as failure to thrive. Well-studied toxins such as aluminum, lead, mercury, and MSG also greatly impact this factory. This is one reason those with known mitochondrial disorders are discouraged from eating foods with pesticides, MSG, and aluminum. Ultimately, anyone with multiple risk factors is especially prone to mitochondrial dysfunction.
Monitor for oxalates, high taurine, MMA, and/or methionine levels as well as low cholesterol.
Ethanolamine and the ... ..more
Summary of analogies used in methylation community: CEOs: Directs each corporation in organized steps
Supervisors: Enzymes such as MTHFRs, COMT, SHMT, and BHMT
Enzymes are proteins that are produced by living cells and regulate the body’s process to breakdown products, such as ammonia.
Employees: Chemicals, proteins, DNA, etc.
Work tags: Methyl groups (Homocysteine, SAM, Methionine) The Chain Gang: Homocysteine (HCY)
Synopsis of the Cycles
1). Power Plant = Citric Acid Cycle =
Formerly known as the Kreb’s cycle) Recognized as the mitochondrial or energy cycle
2). Garbage Dump (& Recycling) =
The urea cycle, ammonia cleanup & nitric oxide production (heart/blood vessel protection)
3). Better Health 4 Life Corp (BH4) = Communications “AT&T” & toxic waste cleanup Neurotalkers: Dopamine, Serotonin, & Norepi
4). SAM’s Corp. = Methionine Cycle =
The major producer of methyl donors and the passageway to the garbage dump (NOS) & liver via the CBS enzyme
5). Farmer Folate = Folate Cycle =
Homegrown” RNA & DNA, methyl groups and Homocysteine (HCY) regulation
The Meaning of Methylation
Methylation is truly a multi-tasking marvel that allows us to be “healthy and human.” Though this highly intricate process occurs within each cell as well as in the fluid supplying the brain and within the liver, it is responsible for the most vital undertakings throughout body chemistry. Methylation determines who we are, what we look like, and how we behave and it is central to our physical, emotional, and mental wellbeing. Without methylation, we could not survive; hence, it is the perfect pathway to focus on for understanding autoimmune ... ..more
The Citric Acid Cycle AKA “The Power Company” is essential for processing and converting all dietary nutrients (vitamins, minerals, fats, amino acids) into useable forms of energy just as any power industry processes coal, gas, or oil for energy production. If you visualize this cycle as a clock, each hour represents an area in which one nutrient converts into a more compatible form of energy. Depending on digestive function, diet, rate of absorption, and the presence of any genetic quirks, a problem might occur at any point within this clock. This may lead to significant metabolic (chemical processing) imbalances within ... ..more
The Folate Cycle Produces organic, homegrown RNA & DNA. Converts folate into usable forms to keep HCY* in check & sends on to SAM’s for more work tags. *HCY/Homocysteine
The Folate Cycle is the “Organic Farming Region” where everything is homegrown. This Region grows “organic” work tags (methyl groups) and is instrumental in the front-line production of new RNA and DNA. Still, this plantation is a bit old fashioned, employing a chain gang (homocysteine) to help them get the work done. Though rarely considered in everyday life, RNA & DNA are essential to making you unique, as well as directing health ... ..more
High dose #FolicAcid is the worst thing a person with the MTHFR gene mutation should take.
If a doctor tells a person with the #MTHFR gene mutations to take Folic ACID then that doctor does not really understand anything about the #L-Methyl Folate receptors on the Blood Brain Barrier [BBB]. The doctor does not realize that high dose Folic ACID is just going to block up the L-Methyl Folate Receptors on the BBB. When Folic ACID gets into the L-Methyl Folate Receptors it BLOCKS the receptor and it doesn't get into the brain and neither does the L-Methyl ... ..more
The Methionine Cycle is the major work tag (methyl donor) manufacturer. SAMe has over 400 functions in the community. Also serves as the main route through to liver & Waste cycle.
Methionine (SAM) Cycle AKA “SAM’s Corporation,” As SAMe has over 400 known methylation reactions, SAM’s Corporation is the chief work tag producer. It’s also where most of the action occurs since it contains the major thoroughfare to the liver (CBS & transsulfuration). While this often works to its’ advantage, it can also pose a safety risk since failure along this route may result in calamity (see Waste Facility ... ..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
It produces a defective MTHFR enzyme of different varieties i.e. it functions less than optimally, such as performing at only 40% of its capacity, or 70% of its capacity. It can mean you won’t break down toxins or heavy metals well i.e. you could find yourself with high iron, or high copper, or high mercury….etc. High copper can also cause low iron.
The defective enzyme doesn’t break down folate vitamins properly (of which folic acid is the precursor to), which can cause high homocysteine, which can increase your risk of coronary heart disease (arteriosclerotic vascular ... ..more
STEP ONE: Layering in The Foundation
Knowing your Nervous system #dominance is an integral part in establishing the treatment process.
A). Remove or limit triggers:
Processed foods contain excitotoxins, dyes, and #toxic preservatives. It is also crucial to remove obvious food #allergies . Please see Resqua pages on #excitotoxins for more information. This is simply defined and discussed in detail.
B). Begin general support:
Provide a good foundation for your nervous system type and begin nutritional support. Though life threatening reactions would be extremely rare (and to my knowledge, unheard of), moving too quickly can result in more intense symptoms of ... ..more
MULTICHEMICAL SENSITIVITY…and #MTHFR
The MTHFR Enzyme is in charge of making #L-Methyl Folate which is the final product of that enzymatic reaction.
L-Methyl folate [5-MTHF] is needed to convert #HOMOCYSTEINE into #Methionine.
With an insufficient amount of L-Methyl Folate there may be a buildup of HOMOCYSTEINE. Too much Homocysteine can cause all sorts of problems such as:
1. Increased blood clotting
2. Irritation and damage to the intima [inner lining of blood vessels]
3. Interfere with cartilage development and healing
As a result of the elevated HOMOCYSTEINE the person will be at greater risk of ... ..more