What’s All The Fuss About Homocysteine?
What can you do to make sure you homocysteine does not become a problem? If homocysteine is a problem, what do you do?
- First, we need to gain an awareness of how the body uses and metabolizes homocysteine.
- Second, you will want to ensure you are getting enough B vitamins, folate and trimethylglycine (TMG).
B vitamins, folate and TMG all work in the body as cofactors with enzymes. Enzymes need specific cofactors bound to them in order for them to function. Vitamin cofactors make the metabolizing homocysteine possible. It does not matter if you have mutations in enzymes such as methylenetetrahydrofolate reductase (MTHFR) or beta-homocysteine S-methyltransferase (BHMT) that reduce your body’s capacity to metabolize homocysteine. If your body’s enzymes do not have a sufficient amount of vitamin cofactors to use, you are going to run into problems because your enzymes are not working for you, they are working against you.
Managing homocysteine levels through supplementation can help normalize the long term effects of genetic mutations affecting homocysteine metabolism. For example, If you have the C667T MTHFR mutation you will have about 25% higher homocysteine levels than people with a properly functioning MTHFR enzyme. You will benefit from adopting a specific supplementation strategy by ensuring your enzymes will always have access to the necessary vitamin cofactors. Often, medical professionals test homocysteine levels neglecting genetic mutations that are strongly influencing homocysteine levels like MTHFR mutations. We recommend to everyone they get checked to see if they have an MTHFR mutation. MTHFR mutations do not directly cause the problems of too much homocysteine but are the root of the problem. An MTHFR test should be given to anyone who is trying to get pregnant or suspects they may have hyperhomocysteinemia. The metabolically inefficient nature of MTHFR mutations leads to a buildup of homocysteine within the body.
Too much homocysteine leads to hyperhomocysteinemia. A condition increasing the likelihood of adverse events during pregnancy such as pre-eclampsia, placental abruption, neural tube defects (NTDs), Intrauterine growth retardation (IGR), recurrent pregnancy loss, and fetal death in utero. Hyperhomocysteinemia also contributes to the development of cardiovascular issues and mental illness.
At first glance, trying to understand homocysteine can be overwhelming. In the graphic below you can see many reactions taking place. We are going to be focusing primarily on reactions relating to homocysteine (located in the bottom right corner). You can see that methylfolate (5-MTHF) is the end result of the folate cycle (folate → 5-MTHF). The process of converting homocysteine to methionine is called methionine salvage and the converting homocysteine into cysteine is called transsulfuration. We will go over both the processes of methionine salvage and transsulfuration in detail.
The enzyme methionine synthase, along with its cofactor B12, catalyzes the reaction between 5-MTHF and homocysteine. This process produces methionine. If there is not enough B12 available in the system, or not enough 5-MTHF, methionine salvage will take much longer or will not happen at all. Not enough methionine synthase activity leads to less methionine salvage. Less methionine salvage leads to less methionine production and a buildup of homocysteine. When homocysteine begins building up, you become at risk for developing hyperhomocysteinemia that can lead to a variety of health related conditions.
Homocysteine And Methionine
Methionine is an essential amino acid, meaning it cannot be made by the body. The standard American diet contains high levels of methionine because meat contains high levels of methionine. Unless you are vegetarian, vegan, or have a deficiency in hydrochloric acid (HCL) production, you do not need to worry about being deficient in methionine. Methionine plays a role in the formation and maintenance of blood vessels, cartilage, and is an important building block of many proteins such as melatonin (helps you fall asleep) and carnitine (fat metabolism). Foods containing high levels of methionine include:
- Brazil nuts
- Cashew nuts
- Sesame seeds
- Chia seeds
- Sour cream
Methionine is the precursor molecule to s-adenosyl methionine (SAM), the primary methyl donor. Low levels of SAM results in major methylation problems throughout the body. When SAM donates a methyl group it turns into s-adenosyl-l-homocysteine which is then made back into homocysteine.
Homocysteine And Cysteine
Cysteine is made by homocysteine through two metabolic reactions and is the process of transsulfuration. First homocysteine is made into cystathionine, through a reaction between homocysteine and cystathionine beta-synthase (CBS), an enzyme using vitamin B6 as a cofactor. Cystathionine goes through another reaction with another enzyme called cystathionine gamma-lyase (CGL) to produce cysteine. When cysteine reacts within the body is does so through oxidation, meaning it donates electrons to other molecules for the formation of new molecular bonds.
Cysteine is a highly reactive molecule participating in many reactions throughout the body. It contains a sulfur group allowing cysteine to form strong bonds with other molecules. Cysteine contributes in the formation of many functional proteins in the body. The most important of these proteins is glutathione. Glutathione is a powerful antioxidant made from cysteine, glutamate, and glycine. Life without glutathione would not be possible. It is vital for survival.
There are two potential pathways for homocysteine to go down. It can be made into methionine with the help of the MTR and BHMT enzymes or made into cysteine. Depending on the biochemical environment within your cells and within your body overall, one of the two pathways will be given priority over the other. Both pathways require different enzymes and different B vitamins that work together to give your body methionine, cysteine and/or glutathione to use.
There are essential B vitamins we need for our folate and homocysteine metabolism to run smoothly. The major pathway to make homocysteine into methionine requires B12 and the minor pathway requires betaine-homocysteine S-methyltransferase and TMG as a cofactor. Both enzymes responsible for the major and minor pathways transforming homocysteine into methionine require cofactors that are B vitamins (B12 and trimethylglycine) Homocysteine to cysteine requires vitamin B6. If at any time there is too much or too little B vitamins, this system can easily become unstable. Making sure you are getting the proper amount of B vitamins is important for keeping the folate and cysteine pathways functioning optimally.