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BRS2 — Methylation & One-Carbon Metabolism

BRS2(FM1) - Methylation Cycle Efficiency

1. Definition

Integrated regulation of Folate/B12-Dependent Homocysteine Remethylation, Betaine/BHMT Remethylation, SAMe Synthesis, and Methionine Cycle Flux, influencing one-carbon flux, homocysteine recycling, and methyl donor availability.

2. Intervention Breakdown

Food-State Dominant

3. Functional Role

↑ SAMe availability; ↓ homocysteine; ↑ methylation capacity

4. Mechanistic Basis (Implementation of PMs)

Diet-actionable control point regulating one-carbon flux, homocysteine recycling, and methyl donor availability.

PM1 governs Folate/B12-Dependent Homocysteine Remethylation. PM2 governs Betaine/BHMT Remethylation. PM3 governs SAMe Synthesis. PM4 governs Methionine Cycle Flux.

Together, these PMs operationalise BRS2(FM1) as a coordinated methylation and one-carbon control point.

5. Underlying Mechanisms and Requirements

5.1 Cofactors and Substrates

PMCofactorsKC substrates
BRS2(PM1)B2B12, betaine, choline, folate (KC1)
BRS2(PM2)zincB12, betaine, choline, folate (KC1)
BRS2(PM3)magnesiumamino acid support, cysteine, glycine, methionine (KC2)
BRS2(PM4)B2, B6, B12B12, betaine, choline, folate (KC1); amino acid support, cysteine, glycine, methionine (KC2)

5.2 PMs (Primary Mechanisms)

5.3 KCs (Key Constraints)

  • None listed

6. Dietary Levers

Diet
  • B12 ← eggs, liver
  • Betaine ← beetroot, spinach
  • Choline ← eggs, liver
  • Folate ← leafy greens, legumes
  • Methionine ← eggs, meat, fish

7. Lifestyle Levers

Lifestyle
  • Regular meal timing and sleep regularity may support daily one-carbon rhythm context alongside dietary methyl-donor intake.
  • Stress and recovery patterns may influence methylation demand indirectly; dietary substrate remains primary for this FM.

8. Scoreable Inputs & Modulation Signals

These inputs are used within the BRAIN Diet ontology to generate evidence-constrained estimates of plausible BRS2 support. They are not direct measures of clinical efficacy.

Scoreable Input Categories
Input CategoryExample InputsFunctional Relevance
Functional Property Potentialsmethyl_donor_pattern; transsulfuration_support; choline_phospholipid_contextMay support methylation cycle efficiency.
Realised Functional Statesconsistent_methyl_donor_coverage; homocysteine_modulation_contextMay reflect integrated FM support at recipe level.
Substance / Nutrient Signalsfolate; B12; choline; betaine; methionine; omega-3Nutrient signals linked to dietary interventions for this FM.
Preparation Transformationsminimally_processed; whole_food_matrixMay preserve methyl-donor and cofactor density.

9. References

  1. Collaboration (1998)
  2. Tao Huang et al. (2015)
  3. Oulhaj et al. (2016)