SAM-e (S-Adenosylmethionine).

Tosylate and disulfate tosylate salts stabilise the identical S-adenosyl methionine molecule, differing in shelf stability rather than in what is absorbed. Listing both counts one active twice.

After SAMe donates its methyl group it becomes homocysteine, and 5-methyltetrahydrofolate is the donor that turns homocysteine back into methionine. Without folate that recycling loop stalls and homocysteine accumulates.

Folate carries the one-carbon unit that regenerates methionine, the precursor from which SAMe is made. The methionine and folate cycles are two halves of one loop.

Methionine synthase needs methylcobalamin to transfer the methyl group from folate to homocysteine. Low B12 traps folate in its methyl form and slows regeneration of the SAMe precursor.

Cystathionine beta-synthase and cystathionine gamma-lyase both use pyridoxal 5-phosphate to move homocysteine onward toward cysteine. B6 opens the exit route from the methionine cycle.

Betaine homocysteine methyltransferase uses betaine to remethylate homocysteine to methionine without folate or B12. It is the second and parallel route back to the SAMe precursor.

Methylenetetrahydrofolate reductase carries an FAD cofactor derived from riboflavin, and its activity is riboflavin sensitive, particularly in people with the common thermolabile variant. Riboflavin therefore sets how much methylfolate reaches the cycle.

SAMe is made by joining methionine to ATP, and that enzyme requires magnesium as part of the Mg-ATP complex. Magnesium status is a background condition for making SAMe endogenously.

The PEMT route makes phosphatidylcholine by transferring three methyl groups from SAMe, so dietary choline spares SAMe from that demand. Choline is also the precursor of betaine, which feeds remethylation.

Guanidinoacetate methyltransferase consumes a large share of the body's SAMe to make creatine. Supplying creatine directly reduces that demand and leaves more methyl capacity for other reactions.

Homocysteine produced downstream of SAMe can be converted through cystathionine to cysteine, the limiting residue for glutathione. NAC supplies that residue directly, so the two converge on the same pool.

Cysteine generated from the methionine cycle by way of SAMe is the rate-limiting input to glutathione synthesis. The two sit at opposite ends of one sulfur pathway.

5-HTP raises serotonin synthesis directly while SAMe supports monoamine methylation and turnover, so serotonergic tone can add up beyond what either label implies. This is a combination to disclose rather than promote.

St. John's Wort raises synaptic monoamine availability and induces CYP3A4, so pairing it with SAMe both adds serotonergic effect and shifts the clearance of other actives. Flag rather than stack.

Catechol-O-methyltransferase consumes a SAMe methyl group each time it inactivates a catecholamine made from tyrosine. More catecholamine turnover means more methyl demand on the same pool.

Methionine adenosyltransferase condenses methionine with ATP to make S-adenosylmethionine, so methionine is the direct precursor and ATP supply is the second input. Everything downstream of SAMe is limited by that step. Taking the finished molecule bypasses the step rather than adding to it.

Serine hydroxymethyltransferase moves a carbon from serine onto tetrahydrofolate, and that carbon is what eventually remethylates homocysteine back to methionine. Serine is the main dietary entry point for one-carbon units. Without it the folate cycle has less to hand over.

Homocysteine left after a methyl transfer can go down the transsulfuration route to cystathionine and then cysteine, and SAMe itself is the allosteric activator that opens that route at cystathionine beta-synthase. So SAMe status decides how much homocysteine is committed to cysteine rather than recycled. Cysteine then feeds glutathione synthesis.

Both transsulfuration enzymes, cystathionine beta-synthase and cystathionine gamma-lyase, require pyridoxal 5-phosphate. Without it, homocysteine cannot exit the cycle towards cysteine. The active coenzyme form is what the enzymes bind directly.

Cysteine produced by transsulfuration is oxidised through cysteine sulfinic acid to hypotaurine and then taurine. That places taurine two steps downstream of the same sulfur that SAMe hands off. The link is pathway position, not a measured combination effect.

Phosphatidylethanolamine N-methyltransferase adds three methyl groups in a row to make phosphatidylcholine, and each one comes from SAMe. That single enzyme is among the largest consumers of methyl groups in the liver. A formula that pushes membrane phospholipid synthesis is drawing on the same methyl pool.

The final step of melatonin synthesis is an O-methylation of N-acetylserotonin by acetylserotonin O-methyltransferase, and SAMe donates that methyl group. Methyl supply is therefore upstream of the finished hormone. This describes the pathway and does not imply that supplemental SAMe raises melatonin output.

Carnitine synthesis starts from trimethyllysine, made by three SAMe-dependent methylations of a protein-bound lysine residue. Methyl-group supply sits at the front of that pathway. Dietary carnitine bypasses it, which is why the relationship matters more to endogenous synthesis than to a supplemented intake.

Two steps in the ubiquinone biosynthetic sequence, catalysed by COQ3 and COQ5, are SAMe-dependent methylations that build the benzoquinone head group and its methoxy substituents. Methyl-donor supply is thus part of endogenous CoQ10 production. Supplemental CoQ10 enters downstream of those steps.

SAMe is decarboxylated to dcSAMe, which donates the aminopropyl group that spermidine synthase attaches to putrescine. That is a distinct fate from methyl donation and it consumes SAMe stoichiometrically. Polyamine synthesis and methylation therefore compete for the same molecule.

Nicotinamide N-methyltransferase methylates nicotinamide using SAMe, producing N1-methylnicotinamide for excretion. A large nicotinamide load therefore draws methyl groups away from other acceptors. This is a well-described competition for the shared methyl pool, and it runs in the other direction too.

Methionine synthase and betaine-homocysteine methyltransferase both use a zinc centre to activate the thiol of homocysteine before the methyl group is transferred. Zinc is structural to the chemistry, not incidental. Ordinary intakes cover it, so this describes the pathway rather than a supplementation pairing.

Glycine N-methyltransferase methylates glycine to sarcosine using SAMe, and it exists largely to burn off excess methyl groups and hold the SAMe to SAH ratio steady. It is one of the highest-capacity SAMe-consuming enzymes in the liver. Glycine supply is therefore part of how the body regulates rather than depletes methylation.