Part 5: Homocysteine and the Reverse Reaction Back to SAH

Part 5: Homocysteine and the Reverse Reaction Back to SAH

I’ve discussed the two recycling pathways of Homocysteine using MTR and BHMT, as well as the clearance pathway via the transsulfuration pathway and the CBS enzyme. In this post, I’ll discuss a fourth pathway or fate of Homocysteine that may be one of the most over looked fates of Homocysteine, yet can have the potentially greatest impact on our health. The pathway I’m referring to is the reverse pathway from where Homocysteine came from. Homocysteine once recycled via MTR or BHMT is converted to Methionine. Methionine is then converted to SAM VAA the MAT enzyme. SAM than participates in a Methylation reaction giving up its methyl group and becomes s-adenosylhomocysteine (SAH). SAH is than rapidly converted to Homocysteine and Adenosine via the enzyme (AHCY). However, the Thermodynamic Equilibrium reaction catalyzed by AHCY favors the reverse reaction of Homocysteine and Adenosine making SAH. Meaning, that SAH is a more sensitive marker for vascular inflammation than HCY. HCY could appear normal and yet SAH be elevated due to the favor of the RXN back toward SAH. So in this situation as Homocysteine levels build, the flow HCY will be back towards SAH, especially if there are hormones in the recycling or clearance pathways. Research has shown that when HCY is high there will be HIGH SAH as well. Interestingly, lowering of HCY does not necessarily correlate with lowering of SAH. Which is why, lowering HCY with vitamins doesn’t necessarily correlate with decreased vascular events. You can lower your HCY by supporting the three other pathways but that does not mean you’ve lowered SAH. SAH could still be elevated due to AHCY...
Part 4: Homocysteine and the Transsulfuration Pathway

Part 4: Homocysteine and the Transsulfuration Pathway

I’ve covered two of the four possible fates of homocysteine. The post will cover the third possible fate and that is the shunting of homocysteine into the transsulfuration pathway. When there is optimal levels of SAM or elevated levels of oxidative stress, the will shift the bulk of homocysteine to the Transsulfuration pathway to provide glutathione, the body’s major antioxidant, as well as other important reactions I won’t be covering in today’s post. This isn’t an all or none response, just a change in the primary flow of the homocysteine. Homocysteine is converted to cystathionine in the first step of the transsulfuration pathway. Two possible pathways/enzymes can be used to get to cystathionine.  The enzyme Cystathionine Beta Synthase (CBS) is used in the presence of Serine to produce Cystathionine and H2O.  The enzyme Cystathionine γ-Lyase (designated as CTH or CSE) is used in the presence of Cysteine to produce Cystathionine and Hydrogen Sulfide. Both reactions require adequate levels of B6. Elevated levels of SAM, Zinc and Hydrogen Peroxide will promote this reaction and Peroxynitrate and Testosterone will inhibit this enzyme. SAM elevations will promote CBS enzyme upregulation by inhibiting the MTHFR and BHMT enzymes, essentially reducing the recycling pathways. SAM will have a stimulatory effect on CBS as well. There are a few SNPs of the CBS enzyme that have been identified. There is some controversy whether these SNPs upregulate enzyme activity or downregulate enzyme activity. Clinically, I’ve seen numerous patients with CBS mutations C677T and A360A that have high levels of homocysteine, the opposite of what we should expect if these are upregulations. In searching the research, there...
Part 3: (Homocysteine) The BHMT Pathway

Part 3: (Homocysteine) The BHMT Pathway

So I’m back with part 3 of our Homocysteine blog series.  In part 2, I covered the primary recycling pathway of Homocysteine in the body which utilizes MTHFR, MTR, Methylation and Zinc to produce Methionine and THF. Because Methylation is such a critical process in the body, there is a backup process for recycling Homocysteine that occurs in the liver and kidneys. This backup process utilizes an enzyme called BHMT. BHMT utilizes Betaine (trimethylglycine from Choline) and Zinc to catalyze the reaction. Betaine is the methyl donor transferring a methyl group to Methionine. Out of the reaction Methionine and DMG (Dimethylglycine) are produced. The Methionine is once again used to produce SAM and DMG is used to produce Sarcosine. Low levels of Zinc, Betaine and/or Choline can slow this reaction. There are BHMT SNPs which can reduce this enzyme’s function. Glucocorticoids can promote the activation of this enzyme. Elevations of SAM and DMG will inhibit BHMT activity. This is a great backup system to support Methylation in the liver and kidney, but this isn’t happening in the rest of the body. Upregulation of this pathway because of blocks in the primary pathway can divert Choline and Betaine away from other important actions to support this pathway. Betaine is produced from Choline or consumed in the diet. Natural foods like beets and spinach are rich in Betaine. Grains are rich in Betaine as well, but not a great source due to their inflammatory effects. So, if increased use Betaine via BHMT pathway and reduced intake in diet, than the body will synthesize it from choline. Heavy conversion of Choline to...
Part 2: The Four Pathways of Homocysteine – Are One Or More of Your Pathways Blocked?

Part 2: The Four Pathways of Homocysteine – Are One Or More of Your Pathways Blocked?

In my last post on homocysteine I discussed homocysteine as an extremely important lab marker that is rarely run. I discussed the optimal range being between 6-8 (some would argue 4-8). I discussed how levels above and below the optimal range can create health challenges by hindering methylation. In this post I want to discuss one of the four pathways of homocysteine in the body. In Part 3 and Part 4 I will describe the other pathways. An elevated homocysteine level is one of the more common findings I see in people with chronic healthcare problems. Elevated homocysteine has been shown to be a contributing factor in vessel damage, high blood pressure, cardiovascular disease, stroke, migraines, Alzheimer’s disease, dementia, macular degeneration, and cancer. So, step one is to make sure you have your homocysteine levels evaluated. The next step is to determine if your level is in the optimal range. And the third step is to determine if it is not in the normal range, why and how to address getting it within range. Homocysteine is critical for health. We need it. It is part of so many vital processes in the body. But if it is high or low, we want to know why. If homocysteine is elevated we can than assume that there is a block in 3 of the 4 possible directions homocysteine can travel once it is formed. If there is a block in one or more of the pathways, homocysteine can become elevated and create damage.   There are four possible fates of homocysteine once it is formed. It can be recycled to methionine via...
The Most Important Blood Test That Is Rarely Ever Run!

The Most Important Blood Test That Is Rarely Ever Run!

The simple blood test that could save your life and why it is rarely ever performed. Did I get your attention? The simple test that could save your life and give you a better indicator of your current state of health is one that is rarely ever performed. What is it? It’s called homocysteine. Most patients have never heard of it. Most doctors never run the test even with their sickest patients. So if doctors don’t run the test, and most people have never heard of it, why would I say getting this test performed could save your life? Read on! What Is Homocysteine? Homocysteine is an amino acid that is broken down from the proteins in our foods directly or made as a result of methylation reactions involving S-adenosylmethionine (SAM). Homocysteine is a critical amino acid needed for multiple processes in the body. One of the most important uses for homocysteine is it’s conversion to methionine which is the substrate for SAM. SAM is the main methyl donor in the body and responsible for 200 plus reactions in the body that occur millions of time per second in our body. I’ve written about methylation and it’s role in body function, dysfunction, disease, and degeneration in other posts. Today I want to discuss homocysteine. It’s importance in our health function and the rate at which we age is so important that this one post may actually wind up being a 2 or 3 post series. Homocysteine plays a pivotal role in the balance between two important pathways in the body; the methionine cycle and the Transsulfuration pathway. The methionine cycle...
Methylation Madness Seminar – Early Bird Registration Is Closing Soon – Don’t Miss Out on the Chance To Take Your Practice To The Next Level

Methylation Madness Seminar – Early Bird Registration Is Closing Soon – Don’t Miss Out on the Chance To Take Your Practice To The Next Level

Join us for Methylation Madness – Level 1. In this first level you will learn Why Methylation Matters To You and Your Patients.  This first level is all about teaching the basics of the methylation pathway: Folate Cycle Methionine Cycle Biopterin Cycle Unea Cycle Kreb’s Cycle Transulferation Mitochondrial function I’ll give you the basics of all of these cycles so that you can have a working knowledge on Monday morning. We will discuss the major genes affecting these pathways. We will discuss the enzymes that produce and the problems that can inhibit these enzymes from working. I will discuss patient management, supplements, testing and an algorithm for supporting these cases. I’ll review case studies. I’ll review how to use what you’ve learned to get the chronically ill well and make an awesome income. This seminar is about massively shortening you learning curve so that you learn and understand this material and are ready to use it Monday morning. Register today by clicking...

Dr. Balcavage is Featured on High Intensity Health Podcast

Dr. Balcavage, Methylation expert, sat down and talked to Mike Mutzel from HighIntensityHealth.com and discusses Methylation, Histamine and Nutrient-Gene Interactions. Dr. Balcavage dives into the science behind common gene SNPs (single-nucleotide polymorphisms) involved in critical methylation pathways. As you’ll learn, methylation is important for balancing hormones producing neurotransmitters, and making cellular energy. And there are many lifestyle factors that affect methylation (i.e., sleep, exercise, and...
The 20 Minute Rule: The Lifestyle Rule That Is Guaranteed To Shed Pounds, Improve Your Mood and Improve Your Quality of Sleep

The 20 Minute Rule: The Lifestyle Rule That Is Guaranteed To Shed Pounds, Improve Your Mood and Improve Your Quality of Sleep

Too often I hear people and patients say they don’t have time for exercise and fitness. I understand that perception (I’ve heard that little voice in my own head) but the reality is that it’s just the little white lie we keep telling ourselves. It provides a great excuse for why we are not healthy and fit. (Just as I wrote that line my 20 minute timer went off and since it’s Tuesday I just knocked out 15 pull-ups). I fully understand that most people don’t have time or want to take the time to drive to the gym, workout, and then drive home. That’s possibly two hours to try and jam into an already hectic schedule. I get it but let’s make this clear, we all need to perform strength training on a regular basis. For those of you already doing it every day and reaping the rewards, this article is not for you. For those of you not doing strength training regularly, read on! By adopting the twenty minute rule for strength training you don’t need to worry about creating or finding time to go to the gym. You don’t have to waste time driving to and from the gym. You don’t have to go anywhere or get any equipment because your body is your equipment and you are going to exercise wherever you are every 20 minutes. This lifestyle rule is the perfect thing for the person who sits at a desk all day. It will get you up and moving throughout the day. Recent research points the detrimental effects of extended periods of sitting. There...
DNA Methylation and Child Proof Outlet Covers

DNA Methylation and Child Proof Outlet Covers

DNA contains our genetic code for who we are. When we need new proteins, enzymes, and cells, specific areas of the DNA called genes are copied to produce these new products. When DNA is methylated (the addition of a carbon and three hydrogen molecules to the DNA), the ability for the gene to express or be copied is blocked. This prevents unwanted proteins and cells from being replicated. The methyl groups bind to areas on the DNA strand called CpG sites. CpG stands for Cytosine-phosphate-Guanine. The CpG site acts like a plug. If the CpG site is filled with a methyl group, the gene can’t replicate. If there is no methyl group attached to the CpG site the gene can be copied. I’ll use an analogy to make this easier to understand. When I want to use my vacuum cleaner I need to plug it into electricity. There are specific spots in my wall where I can plug the cord in called outlets. Our DNA is a long molecule. There are specific areas on the DNA where replication can occur. The CpG sites signify the areas where replication can occur. When a gene needs to replicate to produce new proteins, messengers molecules called “transcription factors” (the plug of my vacuum) are sent to the DNA to bind to the CpG sites (the outlet). When the two combine, the gene is able to be copied. When my kids were little, we put protective covers on our electrical outlets when we weren’t using them to prevent the kids from sticking things in the outlet and getting an unwanted shock. Methyl groups...
The Top 10 Functions of Methylation

The Top 10 Functions of Methylation

What is methylation and why does it matter?  Methylation is a metabolic process that happens in every cell of the human body and is critical to optimal function. Without methylation life doesn’t exist. Methylation is involved in nearly 200 reactions in the human body. The quality of those methylation reactions ultimately determines our level of health and function. So what is methylation? Methylation is the transfer of a chemical fragment called a methyl group (carbon atom linked to three hydrogen atoms) from one molecule to another. These methyl groups act like keys to turn on and off the 200+ methylation reactions in the body. A molecule that donates a methyl group is termed a methyl donor. The most abundant methyl donor in the body is a molecule called SAM (S-adenosylmethionine). Without adequate SAM production and the actual methylation reactions, our health and function can become mildly to severely compromised. So what does methylation actually do? Here are the top 10 functions of methylation: Gene regulation: Methylation is involved in turning off and on our genes. Methyl donors act like “keys” to turn off and on the expression of the genes. At the root of what causes cancer is hypo or hyper methylation (technically it is a combination of both). Biotransformation: The processing of chemicals within the human body is called biotransformation. Methylation is involved in the process of making and degrading chemicals within our bodies, as well processing as those we consume from our environment (xenobiotics). Production of neurotransmitters: Methylation is required to make neurotransmitters which are the chemicals our nerve cells use to communicate with each other. Without...
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