Homocysteine
Remethylation–transsulfuration branch point
Also searched as Remethylation–transsulfuration branch point.
The same Molecule Feeds Methylation or Antioxidant Defense, and b-vitamin Status Decides Which. Remethylation needs folate and B12; transsulfuration needs B6. That is why a single deficiency can present as either an epigenetic or a redox problem. Raised homocysteine is a marker of the fork being blocked, not a toxin in its own right — lowering it with vitamins has repeatedly failed to reproduce the outcome benefit its epidemiology predicted.
In depth
The junction metabolite — remethylated back to methionine, or committed down transsulfuration to cysteine.
What drives it
One-carbon metabolism reduces it.
Remethylation consumes homocysteine and returns it to methionine. Carried by the intermediary-metabolism and clinical reviews. doi 10.1016/j.molmet.2023.101755 · PMC9967593
Betaine methyl donor reduces it.
A second, independent route out of the fork - remethylation without folate or B12, which is why choline status can partly compensate for folate status and vice versa. Carried by the intermediary-metabolism, micronutrient and clinical reviews (PMC9967593; doi 10.3390/nu18132141; PMC12673670; doi 10.1016/j.molmet.2023.101755). Verbatim: “The pooled estimate of effect for betaine supplementation on plasma homocysteine was a reduction of 1.23 μmol/L, which was statistically significant (95% confidence interval, - 1.61 to - 0.85; P =.01)”. doi 10.3390/nu18132141 · PMID 23997720 · PMC9967593
NAD methylation leak increases it.
SAM consumption yields S-adenosylhomocysteine, which is hydrolyzed to homocysteine. doi 10.3389/fphar.2024.1410479
What it drives
It increases Sulfur clearance route.
The alternative fate - committed to cystathionine and then cysteine. Carried by the intermediary-metabolism and clinical reviews. doi 10.1016/j.molmet.2023.101755 · PMC9967593
It reduces Heart & blood pressure.
A marker of the fork being blocked, not a toxin in its own right - vitamin lowering of homocysteine has repeatedly failed to reproduce the outcome benefit its epidemiology predicted. Carried by the intermediary-metabolism and clinical reviews. doi 10.1016/j.molmet.2023.101755 · PMC9967593
It reduces Memory & focus.
Same caveat - strong association, weak intervention record. Carried by the intermediary-metabolism and clinical reviews. doi 10.1016/j.molmet.2023.101755 · PMC9967593
Blends that modulate it
Each blend page names this pathway and carries the study behind its claim.
See it on the map
Open the causal map to follow this pathway upstream and downstream, arrow by arrow, each with its study.