Detoxification: Phase I Flashcards
What is Phase I Detoxification?
Phase I Detoxification:
Phase I primarily involves the transformation of lipophilic toxins using cytochrome P450 (CYP450) enzymes to make toxins more water-soluble for further processing. The CYP450 + toxin/hormonal reaction creates an active binding site on the toxin, making them more water-soluble but also more reactive for conjugation in Phase II.
What role do CYP450 enzymes play in detoxification?
CYP450 Enzymes:
CYP450 enzymes (50-100 types) detoxify various compounds (e.g., steroids, hormones, toxins, drugs). Increased enzyme production in response to toxins can lead to oxidative stress. When exposed to certain chemicals, the body produces more of the specific enzyme needed to break them down.
What happens if Phase I detoxification increases without Phase II?
Consequence of Imbalance:
If Phase I detoxification (CYP450) increases without Phase II keeping up, reactive intermediates can build up, leading to oxidative stress. Increased production of one enzyme can also reduce the ability to detoxify other substances.
What must Phase I intermediates do to avoid damage?
Phase I to Phase II Transition:
Phase I intermediates must rapidly enter Phase II to avoid damage. Factors like SNPs, diet, and nutrient availability affect detoxification. Phase II is less inducible than Phase I.
How can one support Phase I detoxification?
Supporting Phase I Detoxification:
- Reduce toxic load (e.g., eat organic, minimize exposure to xenobiotics).
- Avoid smoking, alcohol, caffeine, chargrilled/smoked food, and plastics.
- Support with B vitamins and BCAA-rich foods (e.g., whole grains, eggs, meat).
What are the essential cofactors for Phase I detoxification?
Phase I Cofactors:
Essential cofactors include:
- B vitamins (whole grains, legumes, mushrooms, sunflower seeds, pistachios, wild fish, eggs, sea vegetables).
- BCAAs (sources: quinoa, fish, meat, eggs).
- Alcohol depletes B vitamins.
How do SNPs affect Phase I detoxification?
Phase I SNPs:
SNPs in CYP450 genes can increase or decrease enzyme activity, affecting toxin metabolism. This can lead to increased toxicity (speeding up conversion of compounds to reactive intermediary products) or accumulation of unmetabolized toxins.
What does CYP1A1 SNP influence?
CYP1A1 SNP Impact:
CYP1A1 is responsible for deactivating oestrogen and detoxifying toxins like solvents and polycyclic aromatic hydrocarbons (PAHs). SNP G2453T (Rs1799814) ↓ CYP1A1 activity, raising the risk of oestrogen dominance and cancer.
What recommendations are made for those with CYP1A1 SNP?
CYP1A1 SNP Recommendations:
- Avoid chargrilled/smoked meats, smoking, pollutants, and synthetic oestrogens (e.g., parabens).
- Focus on colorful plant foods (phytonutrients and polyphenols), and incorporate sulphur-rich foods (cruciferous and allium vegetables).
What is the role of CYP1A2?
CYP1A2 Function:
CYP1A2 metabolizes caffeine and drugs. SNP rs762551 impacts activity, with the CC genotype (CYP1A2*1C) being slow caffeine metabolizers, who should limit caffeine intake to avoid organ damage.
What are the recommendations for those with CYP1A2 SNP?
CYP1A2 SNP Recommendations:
Avoid all caffeine intake (coffee, tea, chocolate, etc.).
