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Decoding The MAO-A Gene: What It Means For Your Well-being

Aira on June 12, 2024

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Decoding The MAO-A Gene: What It Means For Your Health

Date of Content: May 21, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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Disclaimer: This article does not include all possible risk variants for the MAO-A gene and is for informational purposes only. This article is not intended for diagnosis. Please talk to a healthcare professional if you have symptoms associated with these variants.

What is The MAO-A Gene?

The MAO-A gene, on the X chromosome (Xp11.3), encodes the enzyme monoamine oxidase A, which is essential for breaking down certain neurotransmitters in the brain. The monoamine oxidase A (MAO-A), plays a crucial role in regulating the levels of neurotransmitters such as serotonin, norepinephrine, and dopamine. These neurotransmitters are vital for mood regulation, arousal, and emotional responses.

Common Polymorphisms

The MAO-A R297R synonymous polymorphism is caused by a specific single nucleotide polymorphism (SNP) in the monoamine oxidase A (MAO-A) gene, where the nucleotide at position 941 in the DNA sequence can vary. This SNP is also known by its reference SNP ID, rs6323 G>T.

Impact on Health and Behavior:

  • Aggression and Behavioral Traits: Variations in the MAO-A gene, including the R297R polymorphism, have been studied for their role in aggressive behavior and other psychiatric conditions. Research suggests that specific variants of the MAO-A gene can influence susceptibility to stress and aggression.
  • MAO-A Activity: The R297R  and other polymorphisms are associated with variations in the MAO-A enzyme activity. Some studies indicate that individuals with certain variants may have higher or lower MAO-A activity, which can affect the breakdown of neurotransmitters and subsequently influence mood and behavior.

More on this below.

Which Aspects of Your Health Is Influenced by MAO-A Gene?

Mood Regulation

The MAO-A enzyme breaks down neurotransmitters like serotonin, norepinephrine, and dopamine, which are critical for mood regulation. Abnormal activity of MAO-A can lead to imbalances in these neurotransmitters, contributing to mood disorders such as depression and anxiety. Individuals with specific variants of the MAO-A gene may be more prone to experiencing these conditions.

A 2009 study investigated how genetic polymorphisms in different genes influenced placebo responsiveness in major depressive disorder. Placebo (a treatment with no active ingredient) response varies greatly between individuals. Researchers feel this response works through brain pathways related to rewards controlled by chemicals called monoamines (like serotonin and dopamine). Since genetics strongly influences these chemicals’ activity in the brain, researchers hypothesized that common genetic variations (polymorphisms) that affect the activity of these chemicals would be related to how much a person improves when treated with a placebo for major depressive disorder. Findings revealed that subjects with MAO-A polymorphisms coding for the higher activity form of the enzyme (rs 6323 genotype GT or GG) exhibited a significantly lower placebo response than those with other genotypes.

Behavioral Control

MAO-A activity influences behaviors related to impulse control and aggression. Genetic variations in the MAO-A gene, sometimes called the “warrior gene,” have been associated with increased aggression and antisocial behavior, especially under stressful conditions. These behavioral tendencies can impact social interactions and overall mental health.

In a 2008 study combining psychology and behavioral economics, researchers found that aggression increased in intensity and frequency as provocation levels rose, particularly among individuals with the low-activity MAOA (MAOA-L) variant. Participants punished those they believed had taken money from them by administering varying amounts of spicy sauce. Results showed that the MAOA genotype significantly affected aggressive behavior, especially under high provocation.

Stress Response

The MAO-A gene plays a role in how the body responds to stress. Variants of the MAO-A gene can affect the breakdown of neurotransmitters involved in the stress response, potentially leading to heightened stress sensitivity and altered coping mechanisms. It can influence susceptibility to stress-related disorders.

A 2018 study investigated the influence of stressful life events on aggression among Chinese adolescents in the context of gene polymorphisms. The two genes considered were COMT and MAO-A. Results showed that adolescents carrying the lower-activity-causing MAOA T-allele of the T941G polymorphism showed more aggression with increased interpersonal problems. Additionally, adolescents with the lower activity genotype of the COMT Ala22/72Ser polymorphism and MAOA  T941G T-allele exhibited more aggression under high academic pressure.

Cognitive Function

The MAO-A gene indirectly affects cognitive function by regulating the levels of neurotransmitters that are important for cognitive processes, including attention, memory, and learning. Imbalances in neurotransmitter levels due to altered MAO-A activity can impair cognitive abilities and contribute to neurological conditions.

A 2018 study investigated the association between MAOA gene polymorphisms and attention deficit hyperactivity disorder (ADHD) in Korean children. ADHD, a common neurodevelopmental disorder, is thought to be linked to dopaminergic, serotonergic, and noradrenergic pathways, with MAOA playing a crucial role in neurotransmitter catabolism. Results showed significant associations between the rs6323 G>T polymorphism and ADHD in girls, with the TT genotype acting as a protective factor.

Also read: A Walkthrough of the LifeDNA Personality and Cognition Report

Response to Medications

Individuals with different MAO-A gene variants may respond differently to certain medications, especially those affecting neurotransmitter levels, such as antidepressants (including MAO inhibitors). Understanding one’s MAO-A gene status can help personalize treatment for mental health conditions.

Get your LifeDNA Methylation Genes report to understand your MAO-A gene polymorphisms in more detail. 

Vitamin B2 and MAO-A Enzyme

Vitamin B2, or riboflavin, is a water-soluble vitamin that is vital for many cellular processes. It functions mainly as a precursor to the coenzymes flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD). FMN and FAD are critical for the activity of various flavoproteins. Flavoproteins are a group of proteins that contain a flavin molecule and are mainly involved in reactions related to energy production and detox. These flavoproteins play a significant role in redox reactions. Redox reactions are highly specialized reactions that help animals, including humans, break down complex compounds into usable energy (respiration).

Riboflavin, as a precursor to FMN and FAD, indirectly influences the activity of MAO-A. MAO-A is also a flavoprotein. Like other flavoproteins, it requires FAD as a cofactor for its enzymatic activity. Thus, adequate levels of riboflavin are essential for the optimal functioning of MAO-A.

  • Riboflavin ensures the availability of FAD, which is necessary for the catalytic activity of MAO-A.

Some studies suggest that riboflavin might influence the expression of genes involved in redox regulation, potentially affecting MAO-A activity.

Managing Implications of MAO-A Gene Polymorphisms

Regular Monitoring

Regular psychiatric evaluations and monitoring are crucial for managing symptoms effectively. These check-ups allow healthcare providers to adjust treatment plans as needed, ensuring that the therapeutic approach remains effective and responsive to changes in the individual’s condition.

Therapy

Cognitive Behavioral Therapy (CBT) is effective in managing symptoms of depression, anxiety, and aggression by helping individuals change negative thought patterns. Dialectical Behavior Therapy (DBT) can be beneficial for those with mood regulation issues and impulsive behavior. Family therapy can also provide significant support by improving family dynamics and fostering a supportive environment.

Stress Management

Techniques such as mindfulness, meditation, and relaxation exercises can significantly reduce stress and improve emotional regulation. These practices help individuals manage their responses to stressors, which can mitigate the impact of MAO-A gene variations on behavior and mood.

Diet

Maintaining a balanced diet abundant in fruits, vegetables, whole grains, and lean proteins supports overall brain health. A healthy diet can positively influence neurotransmitter function and mood stability.

Exercise

Regular physical activity is an excellent way to manage stress, improve mood, and reduce symptoms of anxiety and depression. Exercise boosts the production of endorphins and other neurotransmitters that enhance mood and overall mental health.

Sleep Hygiene

Ensuring adequate and regular sleep is vital for maintaining mood and mental health. Establishing a consistent sleep schedule and creating a restful sleep environment can help manage the symptoms associated with MAO-A gene variations.

Genetic Counseling

Genetic counseling provides valuable information about the implications of MAO-A gene variations. Counselors can support individuals and families in understanding these variations and making informed decisions about management and treatment options.

Support Groups

Joining support groups can provide a sense of community and shared experience for individuals with MAO-A gene variations. These groups offer emotional support and practical advice from others facing similar challenges, which can be incredibly beneficial.

Regular Check-ups

Scheduling consistent follow-up appointments with healthcare providers ensures regular monitoring of the symptoms and adjusting the treatment plans as necessary. Regular check-ups also help promptly address changes in the individual’s condition and maintain effective management strategies.

Medication

Antidepressants such as SSRIs and SNRIs can help manage mood disorders linked to MAO-A variations by balancing neurotransmitter levels. MAO inhibitors (MAOIs) might be prescribed in some cases, though they require careful dietary management due to potential side effects. Mood stabilizers can also be beneficial for those experiencing mood swings and aggression, helping to maintain emotional stability.

References

  1. https://medlineplus.gov/genetics/gene/maoa/
  2. https://journals.lww.com/psychopharmacology/abstract/2009/08000/monoamine_oxidase_a_and.12.aspx
  3. https://www.pnas.org/doi/full/10.1073/pnas.0808376106
  4. https://www.frontiersin.org/journals/psychology/articles/10.3389/fpsyg.2018.01079/full
  5. https://www.mdpi.com/1648-9144/54/3/32 
  6. https://www.mayoclinic.org/tests-procedures/cognitive-behavioral-therapy/about/pac-20384610

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I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
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Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
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It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
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I got some pretty useful insight that helped me with my diet.
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*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

The LifeDNA Methylation Genes Report: A Walkthrough

Aira on June 12, 2024

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The LifeDNA Methylation Genes Report: A Walkthrough

Date of Content: May 21, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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The Methylation Cycle in Brief

The methylation cycle is a complex series of biochemical reactions involving various enzymes. To simplify, we will outline the core concept of this cycle to provide a clear context for the roles of specific genes discussed later in this article. This foundational understanding will enhance our exploration of how these genes influence the cycle and various aspects of health and disease.

  • Central to the methylation cycle is the conversion of homocysteine to methionine by the enzyme methionine synthase. 
  • This reaction requires methylcobalamin (a form of vitamin B12) and 5-methyltetrahydrofolate (produced from folate by the enzyme MTHFR). 
  • Methionine can then be converted to S-adenosylmethionine (SAMe), the primary methyl donor in the body. 
  • After donating a methyl group, SAMe becomes S-adenosylhomocysteine (SAH), which is converted back into homocysteine, completing the cycle.
MTR and MTRR

Importance of Healthy Homocysteine Levels

Homocysteine levels are significant because elevated levels of homocysteine, a sulfur-containing amino acid, are associated with an increased risk of cardiovascular diseases, including coronary artery disease, stroke, and peripheral arterial disease. High blood homocysteine levels can damage the lining of arteries, promote blood clot formation, and increase oxidative stress, all of which contribute to the development and progression of atherosclerosis. 

Additionally, elevated homocysteine is associated with other health issues such as cognitive decline, dementia, and certain birth flaws. Monitoring and managing homocysteine levels through diet, lifestyle changes, and, in some cases, medication, can be crucial for maintaining cardiovascular health and preventing related complications.

The LifeDNA Methylation Genes Report

The LifeDNA Methylation report focuses on the methylation cycle of genes to offer insights into various health and wellness aspects.

It is crucial to understand that this report does not diagnose any medical condition, substitute for professional healthcare advice, or provide medical treatment. These genetic variants are prevalent, found in 30-50% of the population, indicating their common occurrence in human DNA.

Genes Covered in the Methylation Report

  • CBS (Cystathionine Beta-Synthase): CBS converts homocysteine into cystathionine, a crucial step in the body’s process of detoxifying itself and producing glutathione, a vital antioxidant.
  • MTHFR (Methylenetetrahydrofolate Reductase): MTHFR plays a critical role in the methylation cycle by transforming a form of folate into another that is crucial for converting homocysteine into methionine, a necessary component for DNA methylation. Read our full analysis of the MTHFR gene.
  • COMT (Catechol-O-Methyltransferase): COMT helps break down neurotransmitters such as dopamine, epinephrine, and norepinephrine, regulating brain chemicals that affect mood and stress responses. Read our full analysis of the COMT gene.
  • MTR (Methionine Synthase): MTR helps complete the production of methionine from homocysteine, using a form of vitamin B12, essential for recycling homocysteine and regenerating methionine.
  • MTRR (Methionine Synthase Reductase): MTRR helps regenerate a form of vitamin B12 that MTR needs to keep producing methionine and manage homocysteine effectively.
  • MTFD1 (Methylenetetrahydrofolate Dehydrogenase 1): MTFD1 manages folate within the body and is crucial for producing certain DNA building blocks.
  • SHMT (Serine Hydroxymethyltransferase): SHMT converts serine and tetrahydrofolate into glycine and another form of folate, linking amino acid and folate metabolism.
  • VDR (Vitamin D Receptor): VDR binds with vitamin D and controls the genes’ activity in immune response and cell growth.
  • ACAT (acetyl-CoA acetyltransferase): ACAT is crucial for cellular energy production. It converts acetyl-CoA into malonyl-CoA, a key molecule in fat metabolism.
  • AHCY (Adenosylhomocysteinase): AHCY breaks down a compound into homocysteine and adenosine, crucial for maintaining the body’s methyl group balance.
  • BHMT (Betaine-Homocysteine S-Methyltransferase): BHMT helps convert homocysteine to methionine using betaine, essential for liver function and fat metabolism.
  • MAO-A (Monoamine Oxidase A): MAO-A breaks down vital neurotransmitters like serotonin and norepinephrine, helping regulate their levels in the nervous system.

NOS3 (Nitric Oxide Synthase 3): NOS3 produces nitric oxide, which helps control blood vessel dilation, blood pressure, and heart health.

How to Interpret Your Report?

To understand the report,  make a note when a variant in these genes is found,as this can indicate potential health risks or areas for improvement. Recommendations include dietary changes, lifestyle adjustments, or supplements. Always consult your healthcare professional or a genetic counselor when reviewing such reports. They can provide expert guidance on the implications of your methylation genes status and recommend personalized interventions based on your genetic makeup.

Non-Genetic Factors that Increase Your Homocysteine Levels

Watch out for these factors that contribute to higher homocysteine levels:

Dietary Changes

Lifestyle Factors

  • Smoking: Tobacco use has been shown to elevate homocysteine levels due to its negative impact on vitamin absorption and metabolism.
  • Excessive Alcohol Consumption: Drinking large amounts of alcohol can interfere with the metabolism of B vitamins, leading to higher homocysteine levels.
  • Lack of Exercise: A sedentary lifestyle can contribute to elevated homocysteine levels. Regular physical activity helps metabolize homocysteine efficiently.

Health and Medical Conditions

  • Kidney Disease: Impaired kidney function can lead to decreased clearance of homocysteine from the blood.
  • Hypothyroidism: An underactive thyroid can interfere with homocysteine metabolism, resulting in elevated levels.
  • Psoriasis: This condition can increase homocysteine levels due to increased turnover of skin cells, which raises the demand for B vitamins involved in homocysteine metabolism.

Additional Factors

  • Age and Gender: Homocysteine levels tend to increase with age and are generally higher in men compared to women.
  • Genetic Factors: Certain genetic variations, such as mutations in the MTHFR gene, can affect the metabolism of homocysteine, leading to higher levels.

Optimize Your Homocysteine Levels Naturally

To optimize homocysteine levels through diet, focus on the following strategies:

  • Increase Folate (Vitamin B9) Intake: Leafy greens (spinach, kale), legumes (beans, lentils), fruits (oranges, bananas), fortified cereals. Folate helps convert homocysteine into methionine, reducing its levels.
  • Boost Vitamin B12 (Cobalamin) Intake: Meat (beef, chicken), fish (salmon, tuna), dairy products (milk, cheese), fortified plant-based milk or cereals. Vitamin B12 is crucial for converting homocysteine into methionine, helping to lower homocysteine levels.
  • Consume More Vitamin B6 (Pyridoxine): Poultry (chicken, turkey), fish (salmon, tuna), potatoes, bananas, and fortified cereals. Vitamin B6 helps convert homocysteine to cysteine, another amino acid, lowering homocysteine levels.
  • Increase Riboflavin (Vitamin B2) Intake: Dairy products (milk, yogurt), eggs, lean meats, green leafy vegetables, and fortified cereals. Riboflavin supports the activity of enzymes involved in homocysteine metabolism.
  • Ensure Adequate Choline Intake: Eggs, beef liver, chicken, shrimp, and soybeans. Choline helps produce betaine, which aids in converting homocysteine to methionine.
  • Limit Alcohol Consumption: Alcohol can impair the function of enzymes involved in homocysteine metabolism and exacerbate high homocysteine levels.
  • Include Antioxidant-Rich Foods: Fruits (berries, oranges), vegetables (broccoli, bell peppers), nuts, and seeds. Antioxidants can help protect against oxidative stress, which may be high with elevated homocysteine.
  • Consider Omega-3 Fatty Acids: Fatty fish (salmon, mackerel), flaxseeds, chia seeds, and walnuts. Omega-3 fatty acids have been associated with lower homocysteine levels and improved heart health.

Incorporating these nutrient-rich foods into your diet can help maintain healthy homocysteine levels and support overall cardiovascular health. Always consult with a healthcare professional before making significant changes to your diet or starting new supplements.

References

  1. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/methylation
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7730869/
  3. https://www.nature.com/scitable/topicpage/x-chromosome-x-inactivation-323/
  4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC26843/ 
  5. https://www.nature.com/articles/npp2012112
  6. https://www.sciencedirect.com/science/article/pii/S0022316622132190
  7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3871626/
  8. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6879356/
  9. https://www.nature.com/articles/s41598-020-74596-7

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
Previous
Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

SHMT Gene And The Methylation Cycle

harvey on May 24, 2024

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SHMT Gene And The Methylation Cycle

Date of Content: May 23, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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The SHMT gene encodes the enzyme serine hydroxymethyltransferase, an enzyme essential for amino acid metabolism and nucleotide synthesis. This enzyme catalyzes the conversion of serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate (5,10-MTHF). This reaction is essential for various biosynthetic processes, including the methylation cycle and the synthesis of  the nucleotides, the DNA and RNA building blocks. 

The SHMT enzyme supports also the production of thymidylate and purines, which are crucial for cell division and genetic stability. It contributes to the pool of methyl groups needed for methylation reactions that regulate gene expression and protein function. Genetic variations in the SHMT gene can affect itsenzyme activity, influencing folate metabolism, homocysteine levels, and overall cellular health. These variations are associated with cardiovascular diseases, neural tube defects, and certain cancers, underscoring the gene’s importance in maintaining metabolic balance and preventing disease.

Overview of the Methylation Cycle

The central theme of the methylation cycle is the conversion of homocysteine, a potentially harmful substance, to methionine, an essential amino acid. The methylation cycle helps keep your homocysteine levels in check. High homocysteine levels can lead to several health issues.

Here are the steps in the methylation cycle involving key enzymes and intermediates:

[1] Conversion of Serine to Glycine [we are here]

  • Enzyme: Serine Hydroxymethyltransferase (SHMT)
  • Reaction: Serine + Tetrahydrofolate (THF) → Glycine + 5,10-Methylenetetrahydrofolate (5,10-MTHF)

[2] Conversion of 5,10-MTHF to 5-MTHF

  • Enzyme: Methylenetetrahydrofolate Reductase (MTHFR)
  • Reaction: 5,10-Methylenetetrahydrofolate (5,10-MTHF) → 5-Methyltetrahydrofolate (5-MTHF)

[3] Conversion of Homocysteine to Methionine

  • Enzyme: Methionine Synthase (MTR)
  • Reaction: Homocysteine + 5-Methyltetrahydrofolate (5-MTHF) → Methionine + Tetrahydrofolate (THF)
  • Coenzyme: Methionine Synthase Reductase (MTRR) keeps MTR active

[4] Alternative Pathway for Homocysteine to Methionine

  • Enzyme: Betaine-Homocysteine Methyltransferase (BHMT)
  • Reaction: Homocysteine + Betaine → Methionine + Dimethylglycine

[5] Conversion of Methionine to SAM

  • Enzyme: Methionine Adenosyltransferase (MAT)
  • Reaction: Methionine + ATP → S-Adenosylmethionine (SAM)

[6] Methylation Reactions

  • SAM as Methyl Donor: SAM donates a methyl group to various substrates (DNA, RNA, proteins, lipids) and becomes S-Adenosylhomocysteine (SAH).

[7] Conversion of SAH to Homocysteine

  • Enzyme: S-Adenosylhomocysteine Hydrolase (SAHH)
  • Reaction: S-Adenosylhomocysteine (SAH) → Homocysteine + Adenosine

[8] Transsulfuration Pathway (Alternative route for homocysteine) 

  • Enzyme: Cystathionine Beta-Synthase (CBS)
  • Reaction: Homocysteine + Serine → Cystathionine
  • Subsequent Reaction: Cystathionine converts to cysteine and other metabolites.

Importance of Healthy Homocysteine Levels

Homocysteine levels are essential because elevated levels of homocysteine, a sulfur-containing amino acid, are associated with an increased risk of cardiovascular diseases, including coronary artery disease, stroke, and peripheral arterial disease. High homocysteine levels can damage the lining of arteries, promote blood clot formation, and increase oxidative stress, all of which contribute to the development and progression of atherosclerosis. 

Additionally, elevated homocysteine is associated with other health issues such as cognitive decline, dementia, and certain birth flaws. Monitoring and managing homocysteine levels through diet, lifestyle changes, and, in some cases, medication can be crucial for maintaining cardiovascular health and preventing related complications.

SHMT

Overview of the Methylation Cycle

The central theme of the methylation cycle is the conversion of homocysteine, the harmful substance, to methionine, an essential amino acid. The methylation cycle helps keep your homocysteine levels in check. As discussed in the earlier section, high homocysteine levels can lead to several health issues.

Here are the steps in the methylation cycle involving key enzymes and intermediates:

[1] Conversion of Serine to Glycine

  • Enzyme: Serine Hydroxymethyltransferase (SHMT)
  • Reaction: Serine + Tetrahydrofolate (THF) → Glycine + 5,10-Methylenetetrahydrofolate (5,10-MTHF)

[2] Conversion of 5,10-MTHF to 5-MTHF

  • Enzyme: Methylenetetrahydrofolate Reductase (MTHFR)
  • Reaction: 5,10-Methylenetetrahydrofolate (5,10-MTHF) → 5-Methyltetrahydrofolate (5-MTHF)

[3] Conversion of Homocysteine to Methionine [we are here]

  • Enzyme: Methionine Synthase (MTR)
  • Reaction: Homocysteine + 5-Methyltetrahydrofolate (5-MTHF) → Methionine + Tetrahydrofolate (THF)
  • Coenzyme: Methionine Synthase Reductase (MTRR) keeps MTR active

[4] Alternative Pathway for Homocysteine to Methionine

  • Enzyme: Betaine-Homocysteine Methyltransferase (BHMT)
  • Reaction: Homocysteine + Betaine → Methionine + Dimethylglycine

[5] Conversion of Methionine to SAM

  • Enzyme: Methionine Adenosyltransferase (MAT)
  • Reaction: Methionine + ATP → S-Adenosylmethionine (SAM)

[6] Methylation Reactions

  • SAM as Methyl Donor: SAM donates a methyl group to various substrates (DNA, RNA, proteins, lipids) and becomes S-Adenosylhomocysteine (SAH).

[7] Conversion of SAH to Homocysteine

  • Enzyme: S-Adenosylhomocysteine Hydrolase (SAHH)
  • Reaction: S-Adenosylhomocysteine (SAH) → Homocysteine + Adenosine

[8] Transsulfuration Pathway (Alternative route for homocysteine)

  • Enzyme: Cystathionine Beta-Synthase (CBS)
  • Reaction: Homocysteine + Serine → Cystathionine
  • Subsequent Reaction: Cystathionine converts to cysteine and other metabolites.

SHMT Gene and the Methylation Cycle

The SHMT gene plays a critical role in the methylation cycle, a crucial biochemical pathway in DNA synthesis, repair, and gene regulation. The enzyme encoded by the SHMT gene, the serine hydroxymethyltransferase, catalyzes the conversion of serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate (5,10-MTHF). This reaction is integral to one-carbon metabolism, which provides the necessary methyl groups for the methylation cycle.

Role of the SHMT Gene in the Methylation Cycle

Production of 5,10-Methylenetetrahydrofolate (5,10-MTHF)

The SHMT enzyme produces 5,10-MTHF andis a crucial intermediate that sets off the methylation cycle. 5,10-MTHF is essential for synthesizing nucleotides for DNA replication and repair.

Regeneration of Methionine from Homocysteine

In the methylation cycle, homocysteine converts back to methionine using methyl groups provided by 5-methyltetrahydrofolate (5-MTHF), derived from 5,10-MTHF. This step is critical for maintaining adequate levels of methionine and S-adenosylmethionine (SAM), the body’s primary methyl donor.

Support for Methylation Reactions

SAM, produced from methionine, is used in numerous methylation reactions, including DNA methylation, which regulates gene expression, as well as the methylation of proteins and lipids. The proper functioning of the SHMT enzyme ensures a steady supply of one-carbon units needed for these reactions.

Interplay with Folate Metabolism

The SHMT gene links the folate cycle with the methylation cycle. Folate (B9), in the form of THF, is required for the SHMT enzyme to produce 5,10-MTHF. Adequate folate levels are thus necessary for the proper function of the methylation cycle and overall cellular health.

Implications of SHMT Gene Polymorphisms

The SHMT1 gene C1420T polymorphism (rs1979277 C>T/G>A), which involves a change from cytosine (C) to thymine (T) at position 1420 in the SHMT1 gene, can impact health in several ways due to its role in one-carbon metabolism and the methylation cycle. Here are the key health impacts associated with this polymorphism:

Folate Metabolism

The serine hydroxymethyltransferase enzyme, encoded by the SHMT gene, converts serine and tetrahydrofolate (THF) to glycine and 5,10-methylenetetrahydrofolate (5,10-MTHF). This reaction is crucial for maintaining proper folate (B9) metabolism. The presence of the T allele at  the SHMT1 C1420T locus may influence the enzyme’s efficiency, potentially altering folate levels in the body.

Homocysteine Levels

The T-allele of the SHMT C1420T polymorphism is associated with higher homocysteine levels, which is a risk factor for cardiovascular and neurodegenerative diseases. This increase in homocysteine levels suggests that individuals with the T-allele may have a higher demand for folate to maintain normal homocysteine metabolism and prevent hyperhomocysteinemia.

Vitamin B12 Interaction

In vitamin B12 metabolism, the SHMT C1420T polymorphism may interact with other genetic factors and vitamin levels to influence health outcomes. Adequate intake of folate and vitamin B12 is essential to mitigate the potential unfavorable effects of this polymorphism.

Genotype-Specific Health Management

Individuals with the SHMT1 1420T allele (rs1979277-A) may benefit from personalized health management strategies, including dietary adjustments to ensure sufficient folate and vitamin B12 intake, regular monitoring of homocysteine levels, and preventive measures for cardiovascular and neurodegenerative diseases.

Get your LifeDNA Methylation Genes report to understand your SHMT and other methylation gene polymorphisms in detail. 

Optimize Your Homocysteine Levels Naturally

To optimize homocysteine levels through diet, focus on the following strategies:

  • Increase Folate (Vitamin B9) Intake: Leafy greens (spinach, kale), legumes (beans, lentils), fruits (oranges, bananas), fortified cereals. Folate helps convert homocysteine into methionine, reducing its levels.
  • Boost Vitamin B12 (Cobalamin) Intake: Meat (beef, chicken), fish (salmon, tuna), dairy products (milk, cheese), fortified plant-based milk or cereals. Vitamin B12 is crucial for converting homocysteine into methionine, helping to lower homocysteine levels.
  • Consume More Vitamin B6 (Pyridoxine): Poultry (chicken, turkey), fish (salmon, tuna), potatoes, bananas, and fortified cereals. Vitamin B6 helps convert homocysteine to cysteine, another amino acid, lowering homocysteine levels.
  • Increase Riboflavin (Vitamin B2) Intake: Dairy products (milk, yogurt), eggs, lean meats, green leafy vegetables, and fortified cereals. Riboflavin supports the activity of enzymes involved in homocysteine metabolism.
  • Ensure Adequate Choline Intake: Eggs, beef liver, chicken, shrimp, and soybeans. Choline helps produce betaine, which aids in converting homocysteine to methionine.
  • Limit Alcohol Consumption: Alcohol can impair the function of enzymes involved in homocysteine metabolism and exacerbate high homocysteine levels.
  • Include Antioxidant-Rich Foods: Fruits (berries, oranges), vegetables (broccoli, bell peppers), nuts, and seeds. Antioxidants can help protect against oxidative stress, which may be high with homocysteine levels.
  • Consider Omega-3 Fatty Acids: Fatty fish (salmon, mackerel), flaxseeds, chia seeds, and walnuts. Omega-3 fatty acids tend to lower homocysteine levels and improve heart health.

Incorporating these nutrient-rich foods into your diet can help maintain healthy homocysteine levels and support overall cardiovascular health. Always consult with a healthcare professional before making significant changes to your diet or starting new supplements.

References

  1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3609604/ 
  2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3936891/

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
Previous
Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

MTRR and MTR Genes and the Methylation Cycle

harvey on May 24, 2024

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Table of Contents

MTRR and MTR Genes and the Methylation Cycle

Date of Content: May 21, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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Disclaimer: This article does not include all possible risk variants for the MTRR and MTR and is only for informational purposes. This article is not intended for diagnosis. Please talk to a healthcare professional if you have symptoms associated with these variants.

Why is the Methylation Cycle Important For You?

The methylation cycle is essential for numerous biological processes and overall health. Protein methylation detoxifies harmful substances, including heavy metals and toxins, thus protecting the body and supporting liver function. 

Methylation  also affects neurotransmitter production and regulation, influencing mood, cognition, and mental health. The methylation cycle helps regulate homocysteine levels, reducing the risk of cardiovascular diseases like heart disease and stroke. Furthermore, it is involved in energy production by synthesizing creatine and carnitine, both essential for metabolism and muscle function. 

Finally, methylation modulates the immune system, supporting the production and function of immune cells, which are crucial for combating infections and diseases. The methylation cycle is fundamental to many aspects of health and well-being.

Importance of Healthy Homocysteine Levels

Homocysteine levels are significant because elevated levels of homocysteine, a sulfur-containing amino acid, are associated with an increased risk of cardiovascular diseases, including coronary artery disease, stroke, and peripheral arterial disease. High homocysteine levels can damage the lining of arteries, promote blood clot formation, and increase oxidative stress, all of which contribute to the development and progression of atherosclerosis. 

Additionally, elevated homocysteine is associated with other health issues such as cognitive decline, dementia, and certain birth flaws. Monitoring and managing homocysteine levels through diet, lifestyle changes, and, in some cases, medication, can be crucial for maintaining cardiovascular health and preventing related complications.

MTR and MTRR

Overview of the Methylation Cycle

The central theme of the methylation cycle is the conversion of homocysteine, the harmful substance, to methionine, an essential amino acid. The methylation cycle helps keep your homocysteine levels in check. As discussed in the earlier section, high homocysteine levels can lead to several health issues.

Here are the steps in the methylation cycle involving key enzymes and intermediates:

[1] Conversion of Serine to Glycine

  • Enzyme: Serine Hydroxymethyltransferase (SHMT)
  • Reaction: Serine + Tetrahydrofolate (THF) → Glycine + 5,10-Methylenetetrahydrofolate (5,10-MTHF)

[2] Conversion of 5,10-MTHF to 5-MTHF

  • Enzyme: Methylenetetrahydrofolate Reductase (MTHFR)
  • Reaction: 5,10-Methylenetetrahydrofolate (5,10-MTHF) → 5-Methyltetrahydrofolate (5-MTHF)

[3] Conversion of Homocysteine to Methionine [we are here]

  • Enzyme: Methionine Synthase (MTR)
  • Reaction: Homocysteine + 5-Methyltetrahydrofolate (5-MTHF) → Methionine + Tetrahydrofolate (THF)
  • Coenzyme: Methionine Synthase Reductase (MTRR) keeps MTR active

[4] Alternative Pathway for Homocysteine to Methionine

  • Enzyme: Betaine-Homocysteine Methyltransferase (BHMT)
  • Reaction: Homocysteine + Betaine → Methionine + Dimethylglycine

[5] Conversion of Methionine to SAM

  • Enzyme: Methionine Adenosyltransferase (MAT)
  • Reaction: Methionine + ATP → S-Adenosylmethionine (SAM)

[6] Methylation Reactions

  • SAM as Methyl Donor: SAM donates a methyl group to various substrates (DNA, RNA, proteins, lipids) and becomes S-Adenosylhomocysteine (SAH).

[7] Conversion of SAH to Homocysteine

  • Enzyme: S-Adenosylhomocysteine Hydrolase (SAHH)
  • Reaction: S-Adenosylhomocysteine (SAH) → Homocysteine + Adenosine

[8] Transsulfuration Pathway (Alternative route for homocysteine)

  • Enzyme: Cystathionine Beta-Synthase (CBS)
  • Reaction: Homocysteine + Serine → Cystathionine
  • Subsequent Reaction: Cystathionine converts to cysteine and other metabolites.

MTR and MTRR in the Methylation Cycle

The MTR and MTRR genes enter the methylation cycle in the third step, which is the conversion of homocysteine to methionine. Methionine is an essential amino acid that plays a crucial role in various bodily functions, including the synthesis of proteins, which are the building blocks of our cells. Methionine is also vital for SAM, a compound that helps with methylation, detoxifies harmful substances, and supports overall cell function. Foods rich in methionine include meat, fish, dairy products, nuts, and seeds.

The MTR gene  produces themethionine synthase enzyme crucial for the methylation cycle. This enzyme catalyzes the conversion of homocysteine, a potentially harmful amino acid, into methionine, an essential amino acid necessary for protein synthesis and other metabolic functions. Methionine is then converted into S-adenosylmethionine (SAM), a key methyl donor involved in numerous methylation reactions that regulate DNA synthesis, repair, and gene expression.

The MTRR gene, encodes for the methionine synthase reductase coenzyme which ensures the continuous activity of methionine synthase enzyme (encoded by the MTR gene). Methionine synthase can become inactive during the conversion of homocysteine to methionine, and methionine synthase reductase reactivates it, allowing the cycle to proceed smoothly. The MTR and MTRR genes maintain proper homocysteine levels and support the methylation cycle, which is vital for many cellular functions and overall health.

How This Can Affect You?

Polymorphisms in the MTR and MTRR genes can directly impact homocysteine levels, and  can therefore influence many health aspects.

Some studies have found that risk variants in the MTR and MTRR genes are associated with difficulties using methylcobalamin, a form of vitamin B12, and producing methionine. Methylcobalamin is a coenzyme that helps convert homocysteine to methionine. Individuals with these risk variants may have lower B12 levels because the MTR enzyme uses B12 more quickly. Vitamin B12 is crucial for DNA synthesis, cell division, red blood cell formation, energy production, mood regulation, and other essential bodily functions. Additionally, those with the risk variants may have higher homocysteine levels, particularly if their B12 levels are low, and elevated homocysteine levels have been associated with an increased risk of cardiovascular problems.

A 2007 study examined the association between MTR (A2756G, rs1805087 A>G) and MTRR (A66G, rs1801394 A>G) gene polymorphisms and levels of total homocysteine in 275 healthy women in labor who delivered full-term normal babies. Results showed that the MTR and MTRR genotypes could predict total homocysteine levels, sometimes depending on the serum folate or cobalamin levels. However, women with  MTR 2756AA had statistically significantly higher total homocysteine levels independently of the other factors. 

Get your LifeDNA Methylation Genes report to understand your MTR, MTRR and other methylation gene polymorphisms in detail. 

Optimize Your Homocysteine Levels Naturally

To optimize homocysteine levels through diet, focus on the following strategies:

  • Increase Folate (Vitamin B9) Intake: Leafy greens (spinach, kale), legumes (beans, lentils), fruits (oranges, bananas), fortified cereals. Folate helps convert homocysteine into methionine, reducing its levels.
  • Boost Vitamin B12 (Cobalamin) Intake: Meat (beef, chicken), fish (salmon, tuna), dairy products (milk, cheese), fortified plant-based milk or cereals. Vitamin B12 is crucial for converting homocysteine into methionine, helping to lower homocysteine levels.
  • Consume More Vitamin B6 (Pyridoxine): Poultry (chicken, turkey), fish (salmon, tuna), potatoes, bananas, and fortified cereals. Vitamin B6 helps convert homocysteine to cysteine, another amino acid, lowering homocysteine levels.
  • Increase Riboflavin (Vitamin B2) Intake: Dairy products (milk, yogurt), eggs, lean meats, green leafy vegetables, and fortified cereals. Riboflavin supports the activity of enzymes involved in homocysteine metabolism.
  • Ensure Adequate Choline Intake: Eggs, beef liver, chicken, shrimp, and soybeans. Choline helps produce betaine, which aids in converting homocysteine to methionine.
  • Limit Alcohol Consumption: Alcohol can impair the function of enzymes involved in homocysteine metabolism and exacerbate high homocysteine levels.
  • Include Antioxidant-Rich Foods: Fruits (berries, oranges), vegetables (broccoli, bell peppers), nuts, and seeds. Antioxidants can help protect against oxidative stress, which may be high with homocysteine.
  • Consider Omega-3 Fatty Acids: Fatty fish (salmon, mackerel), flaxseeds, chia seeds, and walnuts. Omega-3 fatty acids have been associated with lower homocysteine levels and improved heart health.

Incorporating these nutrient-rich foods into your diet can help maintain healthy homocysteine levels and support overall cardiovascular health. Always consult with a healthcare professional before making significant changes to your diet or starting new supplements.

References

  1. https://doi.org/10.1016/j.thromres.2006.05.009
  2. https://www.nature.com/articles/1602810 
  3. https://my.clevelandclinic.org/health/articles/21527-homocysteine
  4. https://medlineplus.gov/genetics/gene/mtr/
  5. https://medlineplus.gov/genetics/gene/mtrr/

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
Previous
Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

CBS Gene and its Influence on the Methylation Cycle

harvey on May 24, 2024

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Table of Contents

CBS Gene and its Influence on the Methylation Cycle

Date of Content: May 20, 2024
Written by: Avanthika Nityanand
Reviewed by: Maarit Tiirikainen, PhD

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Disclaimer: This article does not include all possible risk variants for the CBS gene and is for informational purposes only. This article is not intended for diagnosis. Please talk to a healthcare professional if you have symptoms associated with these variants.

What is the CBS Gene?

The CBS geneis a crucial gene encoding the enzyme Cystathionine Beta-Synthase. This enzyme plays a pivotal role in the metabolic pathway known as the transsulfuration pathway, which converts homocysteine to cystathionine. This conversion is a crucial step in metabolizing sulfur-containing amino acids. It is critical for maintaining proper levels of homocysteine and methionine in the blood.

The CBS gene is on chromosome 21. The functional pathways of the encoded enzyme, Systathionine Beta-Synthase (CBS), involves several vital biochemical processes, including cysteine, glutathione, taurine, and hydrogen sulfide synthesis. These molecules are essential for detoxification, antioxidant defense, and modulation of neurotransmission. Genetic variations in the CBS gene can lead to dysregulation of these pathways and result in elevated homocysteine levels, a condition known as hyperhomocysteinemia. This condition is associated with various health issues, including vascular diseases, neurological disorders, and congenital flaws.

The importance of the CBS enzyme extends beyond merely maintaining amino acid levels; it also impacts overall cellular health and function. Research into the role of CBS has provided insights into the complex interactions between genetics, diet, and disease. It is also a target for therapeutic interventions in diseases with sulfur metabolism disruption. For example, dietary adjustments and supplementation can help manage CBS gene mutations and their systemic effects.

Understanding the function and regulation of the CBS is crucial for comprehending broader aspects of human health and disease, particularly those related to amino acid metabolism and cardiovascular health. Ongoing research continues to reveal the intricate balance required in sulfur metabolism and the potential consequences when there is a disruption in this balance.

CBS

Overview of the Methylation Cycle

The central theme of the methylation cycle is the conversion of homocysteine to methionine, an essential amino acid. The methylation cycle helps keep your homocysteine levels in check. As discussed in the earlier section, high homocysteine levels can lead to several health issues.

Here are the steps in the methylation cycle involving key enzymes and intermediates:

[1] Conversion of Serine to Glycine

  • Enzyme: Serine Hydroxymethyltransferase (SHMT)
  • Reaction: Serine + Tetrahydrofolate (THF) → Glycine + 5,10-Methylenetetrahydrofolate (5,10-MTHF)

[2] Conversion of 5,10-MTHF to 5-MTHF

  • Enzyme: Methylenetetrahydrofolate Reductase (MTHFR)
  • Reaction: 5,10-Methylenetetrahydrofolate (5,10-MTHF) → 5-Methyltetrahydrofolate (5-MTHF)

[3] Conversion of Homocysteine to Methionine

  • Enzyme: Methionine Synthase (MTR)
  • Reaction: Homocysteine + 5-Methyltetrahydrofolate (5-MTHF) → Methionine + Tetrahydrofolate (THF)
  • Coenzyme: Methionine Synthase Reductase (MTRR) keeps MTR active

[4] Alternative Pathway for Homocysteine to Methionine

  • Enzyme: Betaine-Homocysteine Methyltransferase (BHMT)
  • Reaction: Homocysteine + Betaine → Methionine + Dimethylglycine

[5] Conversion of Methionine to SAM

  • Enzyme: Methionine Adenosyltransferase (MAT)
  • Reaction: Methionine + ATP → S-Adenosylmethionine (SAM)

[6] Methylation Reactions

  • SAM as Methyl Donor: SAM donates a methyl group to various substrates (DNA, RNA, proteins, lipids) and becomes S-Adenosylhomocysteine (SAH).

[7] Conversion of SAH to Homocysteine

  • Enzyme: S-Adenosylhomocysteine Hydrolase (SAHH)
  • Reaction: S-Adenosylhomocysteine (SAH) → Homocysteine + Adenosine

[8] Transsulfuration Pathway (Alternative route for homocysteine) [we are here]

  • Enzyme: Cystathionine Beta-Synthase (CBS)
  • Reaction: Homocysteine + Serine → Cystathionine
  • Subsequent Reaction: Cystathionine converts to cysteine and other metabolites.

The CBS gene produces the enzyme cystathionine beta-synthase. This enzyme uses Vitamin B6 (pyridoxine) to convert homocysteine and serine into cystathionine.

Additionally, through the transsulfuration process, cystathionine can be converted into taurine or glutathione. This process is crucial for making cysteine-containing amino acids, which are vital for protein structure, antioxidant activity, detoxification, and metabolic functions.

Importance of Healthy Homocysteine Levels

Appropriate homocysteine levels are essential because elevated levels of homocysteine, a sulfur-containing amino acid, are associated with an increased risk of cardiovascular diseases, including coronary artery disease, stroke, and peripheral arterial disease. High homocysteine levels can damage the lining of arteries, promote blood clot formation, and increase oxidative stress, all of which contribute to the development and progression of atherosclerosis. 

Additionally, elevated homocysteine is linked to other health issues such as cognitive decline, dementia, and certain birth flaws. Monitoring and managing homocysteine levels through diet, lifestyle changes, and, in some cases, medication, can be crucial for maintaining cardiovascular health and preventing related complications.

How Does the CBS Gene Affect the Methylation Cycle?

Genetic variation in the CBS gene can influence the methylation cycle significantly due to its role in processing homocysteine, a sulfur-containing amino acid crucial for methylation reactions. 

Methylation is a biochemical process involving transferring a methyl group (one carbon atom and three hydrogen atoms) onto amino acids, proteins, enzymes, and DNA, which can affect their function and activity. The methylation cycle is vital for numerous cellular processes, including DNA repair, gene expression, and the synthesis of neurotransmitters.

Here are important functions of the CBS enzyme:

Reducing Homocysteine Levels

The enzyme encoded by the CBS gene, cystathionine beta-synthase, catalyzes the first step in the transsulfuration pathway, where homocysteine is converted into cystathionine. This conversion is crucial because it helps regulate the homocysteine level in the body. Elevated homocysteine levels can lead to a variety of health issues, including cardiovascular diseases and neurological conditions. By converting homocysteine into cystathionine, the CBS enzyme indirectly supports the recycling of homocysteine into methionine or its conversion into other sulfur-containing compounds.

Making Glutathione

Furthermore, the transsulfuration pathway facilitated by the CBS enzyme produces essential raw material for glutathione synthesis. Glutathione is a major antioxidant that protects cells from oxidative stress and helps maintain the redox balance within cells, which is crucial for normal cellular function and disease prevention.

Variations in the CBS gene can lead to altered enzyme activity, potentially causing a buildup of homocysteine and a subsequent imbalance in methylation-dependent processes. This dysregulation can impair DNA synthesis and repair, disrupt gene expression, and alter neurotransmitter synthesis, manifesting in various diseases and conditions.

Implications of the CBS Gene Variations

Several studies have looked into the role of the CBS gene variation and their effects on homocysteine levels and other health aspects.

A 2013 meta-analysis of genome-wide association studies (GWAS) involving 44,147 individuals of European descent investigated the CBS gene and 12 other loci for their association with total homocysteine (tHcy) concentrations and coronary artery disease (CAD) risk. This study aimed to determine if genetic polymorphisms linked to tHcy levels correlate with CAD. The results identified 13 loci, including six novel ones, that explained 5.9% of the variation in tHcy levels. However, a genotype risk score (GRS) based on these variants showed no significant association with CAD risk. This suggests that common genetic variants affecting tHcy levels do not influence CAD risk in white populations, thereby challenging the causal relevance of elevated tHcy levels for CAD.

A study from 2010 looked into genetic variation in the CBS gene and how this might influence susceptibility to arsenic-induced disease by affecting arsenic metabolism. In an arsenic-exposed population in Cordoba Province, Argentina, individuals with variant genotypes for CBS SNPs rs234709 and rs4920037 exhibited a 24% and 26% increase, respectively, in the proportion of arsenic excreted as the more toxic monomethylarsonic acid (%MMA) compared to wild-type homozygotes. This variation is comparable to differences observed between individuals with and without arsenic-related diseases in other studies. These findings suggest that CBS polymorphisms play a role in arsenic metabolism and potentially in the risk of arsenic-related diseases.

Get your LifeDNA Methylation Genes report to understand your methylation gene polymorphisms in detail. 

Optimize Your Homocysteine Levels Naturally

To optimize homocysteine levels through diet, focus on the following strategies:

  • Increase Folate (Vitamin B9) Intake: Leafy greens (spinach, kale), legumes (beans, lentils), fruits (oranges, bananas), fortified cereals. Folate helps convert homocysteine into methionine, reducing its levels.
  • Boost Vitamin B12 (Cobalamin) Intake: Meat (beef, chicken), fish (salmon, tuna), dairy products (milk, cheese), fortified plant-based milk or cereals. Vitamin B12 is crucial for converting homocysteine into methionine, helping to lower homocysteine levels.
  • Consume More Vitamin B6 (Pyridoxine): Poultry (chicken, turkey), fish (salmon, tuna), potatoes, bananas, and fortified cereals. Vitamin B6 helps convert homocysteine to cysteine, another amino acid, lowering homocysteine levels.
  • Increase Riboflavin (Vitamin B2) Intake: Dairy products (milk, yogurt), eggs, lean meats, green leafy vegetables, and fortified cereals. Riboflavin supports the activity of enzymes involved in homocysteine metabolism.
  • Ensure Adequate Choline Intake: Eggs, beef liver, chicken, shrimp, and soybeans. Choline helps produce betaine, which aids in converting homocysteine to methionine.
  • Limit Alcohol Consumption: Alcohol can impair the function of enzymes involved in homocysteine metabolism and exacerbate high homocysteine levels.
  • Include Antioxidant-Rich Foods: Fruits (berries, oranges), vegetables (broccoli, bell peppers), nuts, and seeds. Antioxidants can help protect against oxidative stress, which may be high with elevated homocysteine.
  • Consider Omega-3 Fatty Acids: Fatty fish (salmon, mackerel), flaxseeds, chia seeds, and walnuts. Omega-3 fatty acids have been associated with lower homocysteine levels and improved heart health.

Incorporating these nutrient-rich foods into your diet can help maintain healthy homocysteine levels and support overall cardiovascular health. Always consult with a healthcare professional before making significant changes to your diet or starting new supplements.

References

  1. https://doi.org/10.3945/ajcn.112.044545
  2. https://onlinelibrary.wiley.com/doi/10.1046/j.1469-1809.1998.6260481.x 
  3. https://doi.org/10.1016/j.envres.2010.05.001 

Customer Reviews

Christopher Devlin
Christopher Devlin
LifeDNA Customer
Read More
I am so impressed with this service. I have even discussed these recommendations with my health care providers and they are all impressed too! I can’t compare it with other services as I have only tried this but I recommend. Also I think I pulled my genetics in from ancestry too which was super convenient.
Lei'a
Lei'a
LifeDNA Customer
Read More
Great source of information I was looking for a platform to make use of my existing raw data from Ancestry. I’m glad I found LifeDNA. I originally took a DNA test to learn about my roots and it’s great to know that my DNA could also play a big role in my health, diet, and even my skin. Overall, all the reports are incredible.
Shiraz Dole
Shiraz Dole
LifeDNA Customer
Read More
It is crazy how I felt that I had a strong understanding of my bodies needs, but after having my DNA analyzed by the LifeDNA team, I realized that there was so much I still did not know.
Doc Sheila Lim
Doc Sheila Lim
LifeDNA Customer
Read More
I got some pretty useful insight that helped me with my diet.
Previous
Next

*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

Our reports have not been evaluated by the Food and Drug Administration. The contents on our website and our reports are for informational purposes only, and are not intended to diagnose any medical condition, replace the advice of a healthcare professional, or provide any medical advice, diagnosis, or treatment. Consult with a healthcare professional before making any major lifestyle changes or if you have any other concerns about your results. The testimonials featured may have used more than one LifeDNA or LifeDNA vendors’ product or reports.

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