Nutrigenomics and Methylation Overview
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Questions and Answers

What is nutrigenomics primarily concerned with?

  • The interaction between nutrition and genetic expression (correct)
  • The regulation of hormone levels through dietary changes
  • The synthesis of vitamins and minerals in the body
  • The process of detoxifying harmful substances in the liver

    • Which nutrient is NOT important for the methylation process?

  • Choline
  • Folate
  • Vitamin C (correct)
  • B12

    • Which phase of liver detoxification primarily uses cytochrome P450 enzymes?

  • Pre-detoxification
  • Phase I (correct)
  • Phase II
  • Phase III

    • What is the main function of glutathione in detoxification?

    <p>To act as a master antioxidant</p> Signup and view all the answers

    What is the role of SNPs in genetics?

    <p>They are variations that can affect enzyme activity</p> Signup and view all the answers

    Which of the following is a strategy for effective detoxification in clinical practice?

    <p>Minimize exposure to toxins</p> Signup and view all the answers

    How does sulfur-rich food support detoxification?

    <p>By aiding in the sulphation process</p> Signup and view all the answers

    Which of the following disruptors is associated with methylation?

    <p>Insufficient folate</p> Signup and view all the answers

    What is the effect of the CBS C699T SNP on ammonia levels in the body?

    <p>It increases ammonia levels.</p> Signup and view all the answers

    Which of the following is NOT a way to support detoxification in a clinical setting?

    <p>Increase environmental pollutants.</p> Signup and view all the answers

    Which enzyme is NOT involved in the detoxification process?

    <p>Hemoglobin</p> Signup and view all the answers

    What is the primary function of the CYP1A1 gene?

    <p>Detoxifies estrogens and harmful environmental toxins.</p> Signup and view all the answers

    Which of the following symptoms is commonly associated with sluggish liver detoxification?

    <p>Waking between 1–3 am</p> Signup and view all the answers

    What is the primary function of the CYP1A1 gene?

    <p>Detoxifies estrogen and polycyclic aromatic hydrocarbons</p> Signup and view all the answers

    Which SNP variant is associated with reduced CYP1A1 activity?

    <p>rs1799814 (G2453T)</p> Signup and view all the answers

    What is the effect of the rs762551 SNP in the CYP1A2 gene?

    <p>Slow caffeine metabolism leading to increased sensitivity</p> Signup and view all the answers

    Which Phase II reaction is primarily responsible for detoxifying estrogens?

    <p>Glucuronidation</p> Signup and view all the answers

    What is the main role of GST (Glutathione S-transferase)?

    <p>Conjugates glutathione to toxins</p> Signup and view all the answers

    What dietary recommendation is suggested for those with the GSTM1 null variant?

    <p>Support with cruciferous vegetables</p> Signup and view all the answers

    Which function does the SULT (Sulfotransferases) family serve?

    <p>Adds sulfate to toxins</p> Signup and view all the answers

    Which of the following is a recommendation for those with UGT1A1 variants?

    <p>Increase intake of citrus and turmeric</p> Signup and view all the answers

    What is the consequence of increased CYP2E1 activity?

    <p>Higher production of harmful alcohol intermediates</p> Signup and view all the answers

    Which type of foods is recommended to support SULT activity?

    <p>Cruciferous vegetables</p> Signup and view all the answers

    What is the primary function of Phase I detoxification?

    <p>Converts fat-soluble toxins into reactive intermediates</p> Signup and view all the answers

    Which enzyme is NOT involved in estrogen detoxification?

    <p>CYP2E1</p> Signup and view all the answers

    What role does calcium D-glucarate play in detoxification?

    <p>Inhibits beta-glucuronidase activity</p> Signup and view all the answers

    SNPs in which gene can lead to estrogen dominance and increased cancer risk?

    <p>CYP1A1</p> Signup and view all the answers

    Which pathway is primarily responsible for detoxifying steroid hormones?

    <p>Sulfation</p> Signup and view all the answers

    What is the main outcome of Phase II detoxification?

    <p>Conversion to water-soluble forms</p> Signup and view all the answers

    Which nutrient can enhance the detox capacity of GST enzymes?

    <p>Selenium</p> Signup and view all the answers

    Which of the following statements about Phase III detoxification is true?

    <p>It removes toxins primarily via urine and bile.</p> Signup and view all the answers

    What does the GSTM1-null variant imply for detox capacity?

    <p>Reduced detox capacity</p> Signup and view all the answers

    Which enzyme is primarily associated with glucuronidation?

    <p>UGT</p> Signup and view all the answers

    What is the primary function of the CYP450 enzymes in Phase I detoxification?

    <p>Transform fat-soluble toxins into reactive intermediates</p> Signup and view all the answers

    Which support strategy is recommended to facilitate detoxification during Phase I?

    <p>Reduce alcohol consumption</p> Signup and view all the answers

    What does the CBS gene primarily regulate in the transsulfuration pathway?

    <p>Conversion of homocysteine to cysteine</p> Signup and view all the answers

    How does the MTHFR C677T SNP affect methylation?

    <p>Decreases conversion of folate to its active form</p> Signup and view all the answers

    Which nutrient is essential for the function of cytochrome P450 in Phase I detoxification?

    <p>B vitamins</p> Signup and view all the answers

    What is the consequence of having a slow metabolizer (CC genotype) for CYP1A2?

    <p>Increased caffeine metabolism</p> Signup and view all the answers

    What is one of the primary roles of COMT in estrogen detoxification?

    <p>Methylates estrogens for excretion</p> Signup and view all the answers

    Which strategy is recommended to support liver detoxification?

    <p>Increase intake of cruciferous vegetables</p> Signup and view all the answers

    What happens if there is a poor transition from Phase I to Phase II detoxification?

    <p>Accumulation of reactive intermediates</p> Signup and view all the answers

    What is the role of sulfur-rich foods in Phase II detoxification?

    <p>Assist in the detoxification of hormones and toxins</p> Signup and view all the answers

    Study Notes

    Nutrigenomics

    • Studies how nutrition impacts gene function and disease prevention
    • Genes are made of DNA, coding for proteins
    • Phenotype is the observable characteristic from gene expression and environmental influences
    • SNPs (Single Nucleotide Polymorphisms) are single nucleotide variations in DNA that affect gene function.

    Methylation

    • Process of adding a methyl group (CH₃) to molecules important for gene regulation, DNA synthesis, and immune function
    • Important nutrients for methylation: Folate, B12, B6, choline, betaine, and zinc
    • Disrupted by insufficient folate and B vitamins and toxin exposure
    • Examples of disruptors: heavy metals and BPA

    Liver Detoxification Phases

    • Phase I involves cytochrome P450 enzymes converting fat-soluble toxins into water-soluble but often reactive intermediates
    • Phase II involves detoxification pathways that add water-soluble groups to reactive intermediates:
      • Glucuronidation detoxifies oestrogens and NSAIDs
      • Sulphation detoxifies steroid hormones and food additives
      • Glutathione Conjugation removes heavy metals like mercury
    • Phase III involves excreting the detoxified products via bile and kidneys

    SNPs (Single Nucleotide Polymorphisms)

    • Variations in DNA that can affect enzyme activity and protein function
    • MTHFR C677T SNP impacts folate metabolism and can lead to higher homocysteine levels
    • CYP1A1 SNP affects oestrogen metabolism and detoxification of harmful chemicals

    Detoxification in Clinical Practice

    • Minimize toxin load by reducing exposure to toxins
    • Support liver and elimination pathways with fibre, hydration, and antioxidant-rich foods
    • Use herbs like milk thistle to protect the liver
    • Common toxins: BPA, pesticides, heavy metals (mercury, lead), and phthalates.

    Nutrients for Detoxification

    • Crucial nutrients:
      • Glutathione: Master antioxidant needed for Phase II detoxification
      • Cysteine: Rate-limiting amino acid for glutathione production, found in legumes, seeds, and eggs.
      • Sulphur-rich Foods: Cruciferous vegetables like broccoli support sulphation
      • B Vitamins: Essential for supporting both Phase I and II detoxification

    Phase I Detoxification (CYP450)

    • Transforms fat-soluble toxins into more reactive, water-soluble intermediates
    • Key Genes and SNPs:
      • CYP1A1 (rs1799814) Detoxifies estrogens and PAHs, reduced activity increases estrogen dominance and cancer risk
      • CYP1A2 (rs762551) Detoxifies caffeine and estrogens, CC genotype results in slow caffeine metabolism, increasing caffeine sensitivity and liver stress
      • CYP2E1 Detoxifies alcohol and small molecules, increased activity leads to higher production of harmful intermediates from alcohol, which can damage the liver

    Phase II Detoxification (Conjugation)

    • Adds water-soluble groups to reactive toxins from Phase I
    • Key Pathways:
      • Glucuronidation Uses UGT enzymes to detoxify estrogen and NSAIDs
      • Sulphation Uses SULT enzymes to detoxify steroid hormones and neurotransmitters
      • Glutathione Conjugation Uses GST enzymes to detoxify heavy metals and carcinogens

    Phase II Detoxification - Key Genes & SNPs

    • GST (Glutathione S-transferase):
      • Catalyzes the conjugation of glutathione to toxins, especially heavy metals
      • GSTM1 'null' variant results in the absence of GSTM1 leading to reduced ability to detoxify carcinogens and oxidative stress
      • Support with cruciferous vegetables, milk thistle, and selenium:
    • SULT (Sulfotransferases)
      • Adds sulfate to toxins like estrogen and neurotransmitters
      • Variants can affect estrogen detoxification, increasing the risk of hormone-related cancers
      • Increase sulfur-containing foods like garlic, onions, and cruciferous vegetables:
    • UGT (UDP-glucuronosyltransferases)
      • Catalyzes glucuronidation, a major pathway for detoxifying estrogens, NSAIDs, and bilirubin
      • Variants in UGT1A1 can reduce glucuronidation, leading to poor clearance of toxins
      • Increase citrus, apples, and turmeric
    • Use calcium D-glucarate to inhibit beta-glucuronidase (produced by dysbiotic gut bacteria) which can deconjugate estrogens and cause reabsorption

    Summary: Liver Detoxification

    • Phase I (CYP450 enzymes) transforms fat-soluble toxins into more reactive intermediates
    • Phase II (conjugation) neutralizes and detoxifies these intermediates using pathways like glucuronidation, sulfation, and glutathione conjugation.
    • Phase III ensures the elimination of these detoxified substances via bile or urine

    Estrogen Detoxification

    • CYP1A1, CYP1B1, COMT, UGT, and SULT enzymes play crucial roles in processing and safely eliminating estrogens from the body
    • SNPs in these genes can impact hormone balance and detox efficiency

    Detoxification Overview

    • Phases:
      • Phase I: transformation via CYP450 enzymes
      • Phase II: conjugation neutralizing toxins
      • Phase III: excretion removing toxins via bile/kidneys
    • Main function is to convert fat-soluble toxins into water-soluble forms for excretion

    Methylation Continued

    • Addition of a methyl group (CH₃) to a molecule is critical for gene regulation, detoxification, and energy production
    • Key co-factors: Folate, B12, B6, choline, betaine, and zinc
    • Common SNP: MTHFR gene (C677T) Reduces conversion of folate to its active form, affecting methylation

    Transsulphuration

    • Conerts homocysteine into cysteine, therefore supporting glutathione production
    • Key Gene: CBS gene (Cystathionine β-synthase) regulates this process
    • SNP: CBS C699T: Increases conversion to cysteine, leading to potential ammonia buildup
    • Support: Increase zinc, choline, and activated charcoal

    Detoxification - Phase I Continued

    • Transforms fat-soluble toxins into reactive intermediates using CYP450 enzymes
    • Key Genes:
      • CYP1A1 Detoxifies estrogens and PAHs, SNPs can increase estrogen dominance and cancer risk
      • CYP1A2 Detoxifies caffeine, slow metabolizers (CC genotype) should avoid caffeine
    • Support: Avoid smoking, reduce alcohol, and increase B vitamins

    Detoxification - Phase II Continued

    • Conjugates reactive intermediates with water-soluble groups for excretion
    • Pathways:
      • Glucuronidation: Detoxifies estrogens, requires glucuronic acid
      • Sulphation: Detoxifies hormones and toxins, needs sulphur-rich foods like garlic and onions
      • Glutathione Conjugation: Requires glutathione to neutralize heavy metals and oxidative stress

    Estrogen Detoxification Continued

    • Key Genes:
      • CYP1A1: Converts estrogens to less harmful forms (2-OH)
      • CYP1B1: Converts estrogens to more harmful forms (4-OH), increasing cancer risk
      • COMT: Methylates estrogens, deactivating them for excretion
    • Support: Increase cruciferous vegetables, fiber, and avoid BPA, caffeine, and alcohol

    Liver Detoxification Support Continued

    • Phase I to Phase II Transition:
      • Ensure progression from Phase I to II is smooth to prevent accumulation of reactive intermediates
      • B Vitamins: Essential for cytochrome P450 function in Phase I
      • Antioxidants: Protect against free radicals generated in Phase I

    Testing and Recommendations

    • Genetic Testing: Useful for identifying SNPs affecting detoxification pathways.
    • Tests for Poor Methylation:
      • Homocysteine levels:

    CBS Gene and Transsulphuration

    • The CBS gene encodes for an enzyme that converts homocysteine into cystathionine in the transsulphuration pathway
    • The CBS C699T SNP increases activity, leading to a buildup of ammonia

    Detoxification

    • The process by which the body transforms and eliminates toxins, converting fat-soluble toxins into water-soluble compounds for excretion

    Supporting Detoxification

    • Minimize toxin exposure (e.g., reduce environmental pollutants)
    • Support liver detox pathways (with foods like cruciferous vegetables)
    • Optimize elimination (e.g., through proper hydration and fiber intake)

    BPA Toxicity

    • Sources: Plastic packaging, canned foods
    • Conditions: Type 2 diabetes, hormone disruption

    Symptoms of Sluggish Liver

    • Fatigue
    • Poor appetite
    • Intolerance to fatty foods
    • Yellowing of eyes
    • Dark circles under eyes
    • Waking between 1–3 am

    Antioxidant Enzymes

    • Superoxide dismutase (SOD)
    • Catalase
    • Glutathione peroxidase
    • Glutathione reductase

    Phase I Detoxification Continued

    • Involves cytochrome P450 enzymes (CYP450) transforming fat-soluble toxins into reactive intermediates, preparing them for further detoxification in Phase II

    CYP1A1 Gene

    • The CYP1A1 gene detoxifies estrogens and harmful environmental toxins like PAHs
    • The SNP reduces its activity, increasing cancer risk

    Phase II Detoxification Continued

    • Glucuronidation
    • Sulphation
    • Glutathione conjugation

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    Module 2 Nutrigenomics and Detox Revision PDF

    Description

    This quiz explores the concepts of nutrigenomics and the role of methylation in gene regulation and detoxification processes. It covers how nutrition influences gene function, the impact of SNPs, and the liver detoxification phases. Test your understanding of these critical interactions between genes and nutrition.

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