Glycine cleavage system

A four-component lipoyl-relay system that oxidatively decarboxylates glycine, transfers its one-carbon unit to tetrahydrofolate, and regenerates the oxidized H-protein carrier. The P protein loads the aminomethyl intermediate onto the H protein, the H protein carries it to the T protein, the T protein forms 5,10-methylenetetrahydrofolate and ammonium, and the shared L protein reoxidizes the reduced lipoyl arm with NAD+. H-protein lipoylation, glycine-generating pathways, and downstream one-carbon metabolism are separate modules.

The boundary is the four-role catalytic cycle rather than a universal stable complex: P loads the H carrier, T transfers the one-carbon unit to tetrahydrofolate, and a potentially shared L enzyme reoxidizes H. H-protein lipoylation, glycine supply, downstream one-carbon metabolism, regulation, and clinical consequences remain outside the module. Representative members orient family roles and do not prescribe a species-specific composition. ALIGN with YeastPathways (2026-10): GLYCLEAV-PWY has the P (GCV2), T (GCV1) and L (LPD1) reactions, with correct catalysts, but omits the H-protein carrier GCV3 (YAL044C, PMID:9020168), which is added as an exemplar; the YeastCyc reactions are written as H-protein half-reactions and map one-to-one onto the P, T and L parts. S. cerevisiae and S. pombe exemplars were added to all four roles. The eukaryotic system is in the mitochondrial matrix (the yeast and fission-yeast proteins carry mitochondrial targeting signals); no location is asserted because the module also covers bacteria. In yeast it lets cells use glycine as a nitrogen source and supplies one-carbon units, so that mitochondrial SHMT can make serine from glycine (glycine_serine_interconversion). GO-CAM disagreements: YeastPathways_GLYCLEAV-PWY places all activities in cytosol, omits GCV3, and has no causal edges. PomBase 67b1629100001554 types the H protein with GO:0140104 molecular carrier activity, as does this module. The human GCSH review proposes lipoyl-dependent carrier activity under GO:0140104; the Arabidopsis H-protein review (genes/ARATH/GDCH) uses GO:0140104 and proposes the same more specific term. These choices describe delivery of reaction intermediates by the lipoyl arm. They do not treat covalent lipoylation itself as noncovalent binding or assign P-, T- or L-protein catalytic activities to the H protein. The PomBase model's aim22 lipoate-protein ligase activity belongs to H-protein lipoylation, outside this module. Member-review rule: a true but general parent term (process or location, e.g. glycine catabolic process, 2-oxoglutarate metabolic process, cytoplasm, membrane) whose more specific descendant is also retained on the same gene is MODIFY to that descendant, not TOO_GENERAL or KEEP_AS_NON_CORE. The five root organelle terms (GO:0005739, GO:0005783, GO:0005794, GO:0005777, GO:0005764) are excluded: they stay beside the sub-compartment (for example mitochondrion beside mitochondrial matrix), per projects/ORGANELLES.md. Where no descendant is retained, the parent is kept as ACCEPT or KEEP_AS_NON_CORE.