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
Urine & stool changes throughout #detoxification . Oftentimes, the urine will change in color and/or clarity as you layer in important cofactors and #methyl groups. The following rules typically apply and if in doubt, obtain a UTM/UEE or fecal metals. Bear in mind that #cadmium precedes lead whereas #nickel often precedes #mercury. You may also see high cadmium levels due to the presence of #HPylori. Moreover, high viral #titers tend to coincide with the presence of heavy metals. Dr. Yasko has found that in some cases, the mercury and other metals were not eliminated (even with chelation therapy) until the ... ..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
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
1) Biopterin/Neopterin: For those with A1298C mutations, #BH4 (also known as tetrahydrobiopterin) levels are typically quite low. This test provides insight to how low these levels are and why. If neopterin levels are high, then I am considering the possibility of a lingering infection, inflammation or chronic immune response that is preventing #biopterin from being formed. Thus, this test provides information not only potentially low biopterin levels but also why they may be low.
If a doctor simply prescribes BH4 without understanding the need to address the inflammation and chronic infections, it is band-aide treatment over a gaping wound ... ..more
The methylation pathway can be likened to the body’s chief housekeeping and maintenance systems. It is responsible for many of the most complex and vital undertakings throughout the body, occurring each time the body takes one substance and turns it into another. This chemical exchange occurs between enzymes, amino acids, proteins, and other molecules in order to maintain cell function. Methylation regulates gene expression, allowing beneficial genes to function while keeping less desirable genes at bay. It also provides the backbone for the immune system, DNA, RNA, cellular repair, detoxification, hormone regulation, and communication between the cells and ... ..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
Understandably, human beings adapt much more readily to positive reinforcement, avoiding the negative experiences. While there are many approaches to #detox , experience has shown that it takes commitment on par with taking a seminar or, when really ill, getting through a longer flu or hospitalization. It takes an extensive amount of time, energy, and dedication, which is often extremely difficult for those who work full-time and/or have a difficult time slowing down. Regardless of the strategy, if you relegate the process to moments of “when I get time,” you cannot be successful. Many make the mistake of trying to ... ..more