Interconverting amino acid axis with major one-carbon donor role. Serine ↔ glycine via SHMT (serine hydroxymethyltransferase) — donates a methylene to THF for the folate cycle (see folate_one_carbon). Glycine is the dominant inhibitory transmitter in spinal cord + brainstem (strychnine antagonist + tetanus toxin). Threonine catabolism produces glycine + acetyl-CoA via TDH (mostly in newborns; minor in adults). PHGDH (phosphoglycerate dehydrogenase) is the rate-limiting step in serine biosynthesis from 3-phosphoglycerate — overexpressed in some breast / melanoma cancers (one-carbon biosynthesis dependency).
Organ Systems
nervous
immune-hematologic
Pathway Steps
serine → glycine — via SHMT — donates methylene to THF (1C feeder). SHMT interconverts serine and glycine while loading a one-carbon unit onto THF — the major one-carbon source feeding nucleotide synthesis and methylation, so serine/glycine availability is a control point on proliferation.
3-phosphoglycerate → serine — via PHGDH → PSAT1 → PSP (serine de novo synthesis). De-novo serine from the glycolytic intermediate 3-phosphoglycerate (PHGDH rate-limiting) — amplified in several cancers and the reason serine/glycine become conditionally essential when growth/one-carbon demand is high.
threonine → glycine-acetylcoa — via TDH (newborn-dominant) + cleavage. Threonine dehydrogenase is a major threonine catabolic route in the newborn and in rodents (largely silenced in adult humans by a pseudogene), yielding glycine and acetyl-CoA.
Known Modulators
alanine (substrate) — alanine pool. glucose-alanine cycle substrate; gluconeogenic AA