S-adenosylmethionine (SAM)
Universal methyl donor whose level reports methionine availability. SAM binds SAMTOR, which otherwise inhibits mTORC1 through the GATOR1-KICSTOR complex.
Reports how much methyl-donor the cell has. A universal 'methyl donor' molecule whose level reflects how much of the amino acid methionine is available. It binds the sensor SAMTOR, which would otherwise keep mTORC1 suppressed.
SAM binds SAMTOR (Kd ~7 µM); links one-carbon metabolism to mTORC1 independently of the leucine and arginine arms.
TL;DR. S-adenosylmethionine (SAM) appears in 2 curated studies in Oliver's mTOR Atlas: 2 at the molecular level (cells, biochemistry, structure). No study in people is recorded for it in the Atlas yet. It has 2 interactions in the curated pathway model.
In the pathway model
| Interaction | Mechanism | Evidence | Studies |
|---|---|---|---|
| S-adenosylmethionine (SAM) inhibits SAMTOR mechanism: binding · this link in full · on the map table | SAM, a byproduct of methionine, binds SAMTOR and pulls it away from GATOR1 – the proposed way the cell senses how much methionine it has. Worked out in cells; whether this sensor is what matters in a whole animal has not been shown. S-adenosylmethionine, the cell's methyl-donor currency, binds SAMTOR and pulls it off GATOR1 - this is how methionine availability reaches mTORC1. S-adenosylmethionine, the cell's methyl-donor currency, binds SAMTOR and pulls it off GATOR1 - this is how methionine availability reaches mTORC1. Holds under: Single-study edge. Needs independent replication before it is treated as established. plausible in people, not shown directly · emerging, few independent studies | M | GU2017 |
| mTORC1 activates S-adenosylmethionine (SAM) mechanism: transcriptional · this link in full · on the map table | mTORC1 tells the cell to make more SAM. Active mTORC1, acting through the transcription factor c-MYC, raises production of MAT2A, the enzyme that makes SAM, so a growing cell makes more of its main methyl donor. Active mTORC1, acting through the transcription factor c-MYC, raises production of MAT2A, the enzyme that makes SAM, so a growing cell makes more of its main methyl donor. Holds under: Human cell lines and mouse xenograft tumours; acts through c-MYC on MAT2A. Together with SAM-SAMTOR this forms a loop whose behaviour in normal tissue is untested. Single study. plausible in people, not shown directly · emerging, few independent studies | M | VIL2021 |
Evidence at a glance
| Evidence | What it means | Studies |
|---|---|---|
| M | Molecular — cells, biochemistry, structure | 2 |
No direct human evidence in the Atlas for this entity yet — everything below rests on animal or molecular work.
Studies
| Year | Evidence | Study |
|---|---|---|
| 2021 | M | mTORC1 stimulates cell growth through SAM synthesis and m6A mRNA-dependent control of protein synthesis VIL2021 SAMTOR (GU2017) showed the cell can sense S-adenosylmethionine and report it to mTORC1. This study runs the arrow the other way: mTORC1 controls how much SAM the cell makes. Downstream of mTORC1, c-MYC binds intron 1 of MAT2A and raises expression of the enzyme that produces SAM, the cell's main methyl donor; mTORC1 separately increases the protein level of WTAP, the regulatory subunit of the m6A RNA methyltransferase complex. Together these raise m6A methylation of mRNA, which primes the translation machinery for growth. Blocking MAT2A lowers SAM, m6A, protein synthesis rate and tumor growth. |
| 2017 | M | SAMTOR is an S-adenosylmethionine sensor for the mTORC1 pathway GU2017 Extended nutrient sensing beyond amino acids to METABOLITES: SAMTOR reads S-adenosylmethionine (SAM), the cell's methyl-donor currency, linking methionine and one-carbon metabolism to mTORC1. Relevant to why methionine restriction affects aging. |
Related entities
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