Homocysteine
The metabolic crossroads. This amino acid sits at the intersection of methylation and transsulfuration—its level tells you how well both pathways are functioning.
⚖️ Two Fates of Homocysteine
Remethylation → Methionine
- MTR pathway: Methylfolate + B12
- BHMT pathway: Betaine (liver/kidney)
- Regenerates methionine for SAMe production
- Dominant when methylation is needed
Transsulfuration → Cysteine
- CBS enzyme: Requires B6
- Irreversible—exits methylation
- Produces cysteine → glutathione
- Activated during oxidative stress
🔺 Causes of Elevated Homocysteine
B12 Deficiency
MTR enzyme can't function without B12
Folate Deficiency
No methylfolate to donate methyl groups
MTHFR Variants
Reduced methylfolate production
B6 Deficiency
CBS pathway blocked
Kidney Disease
Reduced clearance capacity
Hypothyroidism
Slows methylation metabolism
⚠️ High Homocysteine Health Risks
- • Cardiovascular disease - endothelial damage
- • Stroke - increased clot risk
- • Cognitive decline - dementia risk
- • Pregnancy complications - preeclampsia, NTDs
- • Osteoporosis - impaired collagen
- • Depression - indicates poor methylation
✅ Lowering Elevated Homocysteine
Methylfolate
Direct methyl donor for MTR
Methyl-B12
Cofactor for MTR enzyme
B6 (P5P)
Supports CBS pathway
Betaine (TMG)
Alternative methyl donor
Riboflavin (B2)
Supports MTHFR function
NAC
May help lower levels
Metabolic Connections
Methylation
Homocysteine is recycled back to methionine in the methylation cycle
Vitamin B12
MTR enzyme requires B12 to remethylate homocysteine
Folate
Methylfolate provides the methyl group for remethylation
Vitamin B6
CBS enzyme requires B6 for transsulfuration pathway
Glutathione
Transsulfuration diverts homocysteine toward glutathione
Choline
Betaine (from choline) is alternative methyl donor via BHMT