In the process of methylation, the Cystathionine Beta Synthase (CBS) genes (CBSA13637G, CBS C19150T, CBS C699T and CBS A360A ) produces the cystathionine beta synthase enzyme. The purpose of this enzyme is to take a substance called homocysteine, with the help of Vitamin B6, and turn the homocysteine into other substances. This is called Transsulfuration. However, when there are genetic variants or snps in the CBS genes, this process can be impaired. Watch the video on this page to learn how it works.
The first step of Cystathionine Beta Synthase (CBS) is to turn homocysteine into cystathionine, which ultimately produces glutathione, the master antioxidant that protects you from damaging free radicals and environmental toxins.
However, there can be problems with this process if there are what are called SNPs (Single Nucleotide Polymorphisms), also sometimes called variants or defects. The video will explain what SNPs are and how they impact the production of the enzyme.
If the genes you inherited from your parents are not what is considered “normal” the CBS gene may not work as it should because of the SNPs in the CBS genes.
There is ongoing research as to what genetic SNPs do in the CBS genes. There are some researches who think it causes the homocysteine to move “too quickly” and other research shows it may hold it back from going down the pathway. (see video)
The NutriGenetic Research Institute will be researching this and providing our findings as they are available.
It’s possible that different CBS genes, when they have SNPs, cause the conversion to slow down, while others may speed it up.
Nonetheless, if someone has some variants or SNPs in the CBS genes, further testing is advised. You may want to work with a health professional to measure your homocysteine, cysteine and the urine sulfites and sulfates.
Variants or SNPs in the CBS genes could result in:
• Low or high homocysteine
• Anxiety or panic attacks
• Diminished glutathione levels
• Excess in ammonia (a by-product of amino acid metabolism)
• Excess sulfites and sulfates
Many practitioners believe that CBS polymorphisms should be addressed first, before addressing other methylation issues, because increasing methylation may create an increase in sulfites and ammonia. This may have detrimental health effects.
The CBS defect can be made worse by variants or SNPs in MTHFR A1298C & NOS. This is because BH4 (in which production is commonly affected by A1298C) and nitric oxide are used to help clean up ammonia. When BH4 supply is limited, the body prioritizes detoxification of excess ammonia above the production of neurotransmitters, causing possible disruptions in mood and brain function. It requires two BH4 molecules to detoxify one ammonia molecule, and if BH4 and NO are compromised, it will exacerbate ammonia detoxification issues.
Another potential problem with CBS up-regulations besides the inhibition of normal glutathione activity, is that there may be a very high loss of methyl groups because they are drawn down through the up-regulated CBS pathway. In this way, CBS up-regulations behave like a toilet that is broken: the water does not refill, and instead flows down the drain continuously. Some information on the internet implies that the CBS699T is an upregulation, although this is being debated.
If there is upregulation, this may create a problem, because methyl groups are essential for other methylation reactions at other critical junctions. Not only would someone with a CBS up-regulation be losing methyl groups, as well as the primary antioxidant defense in every cell (glutathione), any additional methyl groups from diet or supplementation could cause a potential surge in CBS up-regulations. The result of this situation is a potential toxic overload of many substances, such as ammonia, sulfite, sulfate and hydrogen sulfide, and whatever else that comes along for the ride. This can also create excess glutamate, which is an excitatory neurotransmitter, and create stress and potentially over stimulate the adrenal glands.
This is why taking methyl folate or Methyl B12 when you find you have an MTHFR variant can backfire. This is truly a 3D chess game, and difficult to figure out yourself.
It may be best to see a health care professional to guide you through this intricate and sometimes confusing process.