1.4.1.27	metabolism	isotopic labeling to explore the in vitro and in vivo metabolic fate of the 2-carbon from [2-13C]glycine and [2-13C]serine. As the 2-carbon of glycine and serine is decarboxylated and catabolized via the GCS, the original 13C-labeled 2-carbon is transferred to tetrahydrofolate and yields methylene-tetrahydrofolate in the mitochondria. In hepatoma cell-lines, 2-carbon from glycine is incorporated into deoxythymidine, species of purines (deoxyadenine and deoxyguanine), and methionine	759374	
1.4.1.27	metabolism	isotopic labeling to explore the in vitro and in vivo metabolic fate of the 2-carbon from [2-13C]glycine and [2-13C]serine. In healthy mice, incorporation of GCS-derived formate from glycine 2-carbon is found in serine, methionine, dTMP, and methylcytosine in bone marrow DNA. Labeled glycine 2-carbon directly incorporates into serine, adenine and guanine (at C2 and C8 of purine) in the cytosol	759374	
1.4.1.27	metabolism	liver mitochondria actively catalyze the cleavage of glycine into methylene-THF, CO2, and ammonia, but fail to appreciably catalyze CO2 formation from the alpha-carbon of glycine. The one-carbon compound derived from glycine in the avian livers is utilized largely for the synthesis of uric acid. The yields of 14C-hypoxanthine from 14C-glycine, especially from glycine-2-14C, are significantly increased by the addition of mitochondria to the soluble liver fraction, and under these conditions the ratio of the yields of 14C-hypoxanthine from glycine-l-14C and 2-14C rises to 1:2.3	758693	
1.4.1.27	metabolism	the amino group of glycine is retained in the intermediate and released as ammonia in the second partial reaction catalyzed by T-protein. The formation of ammonia accompanies the stoichiometric formation of 5,10-methylenetetrahydrofolate from the methylene carbon of glycine and tetrahydrofolate. The reaction proceeds through a sequential mechanism. Km values for the intermediate complex and tetrahydrofolate are 2.2 and 50 microM, respectively. In the absence of tetrahydrofolate, T-protein catalyzes the stoichiometric formation of ammonia and formaldehyde from the intermediate although the velocity is extremely low. The addition of tetrahydrofolate increases the rate about 2400fold	759450	
1.4.1.27	metabolism	the enzyme is one of the four components that form the glycine cleavage complex (GCS), essential for the synthesis of C1 (one-carbon units) for cell metabolism, by the oxidative cleavage of glycine. The glycine cleavage complex (GCS), in cooperation with GCA (serine hydroxymethyltransferase) regulates the endogenous levels of glycine and C1 units in the cell. This system comprises four loosely associated proteins, namely GcvP (a pyridoxal phosphate-containing protein), GcvH (a protein that carries aminomethyl intermediate), GcvT (protein required for tetrahydrofolate-dependent reaction) and GcvL (a lipoamide dehydrogenase). GcvP decarboxylates glycine and relocates the remaining methylamine moiety to the lipoyl group of GcvH	764259	
1.4.1.27	physiological function	construction of a genome-scale model of human cell metabolism to investigate the potential metabolic alterations in cells using net zero ATP glycolysis. A pathway for ATP generation involves reactions from serine biosynthesis, one-carbon metabolism and the glycine cleavage system, and is transcriptionally upregulated in an inducible murine model of Myc-driven liver tumorigenesis. This pathway has a predicted two-fold higher flux rate in cells using net zero ATP glycolysis than those using standard glycolysis and generates twice as much ATP with significantly lower rate of lactate, but higher rate of alanine secretion	760049	
1.4.1.27	physiological function	deletion of the gcvT homolog, i.e. T-protein, in attenuated and virulent Francisella tularensis strains. Deletion mutants are auxotrophic for serine but behave similar to wild-type strains with respect to host cell invasion, intracellular replication, and stimulation of TNFalpha. The glycine cleavage system is required for the pathogenesis of virulent Francisella tularensis in a murine model. Deletion of the gcvT gene delays mortality and lowers bacterial burden, particularly in the liver and bloodstream	759738	
1.4.1.27	physiological function	glycine cleavage system and cAMP receptor protein coregulate Cas3 of the CRISPR/Cas system and contribute to the defence against invasive genetic elements. Silencing of the glycine cleavage system encoded by the gcvTHP operon reduces Cas3 expression. Addition of N5,N10-methylene tetrahydrofolate activates Cas3 expression. A cAMP receptor protein encoded by Crp activates Cas3 expression via binding to the Cas3 promoter in response to cAMP concentration. The glycine cleavage system regulates Cas3 through association with cAMP receptor protein	760231	
1.4.1.27	physiological function	H-protein of the glycine cleavage system localizes into vesicles in the cell of Trimastix. When overexpressed in yeast, H- and P-protein are transported into mitochondrion. The first 16 amino acids of H-protein are necessary for this transport	760050	
1.4.1.27	physiological function	in an LpdA deletion mutant, inducible GCV enzyme activity is not detected. A D-3-phosphoglycerate dehydrogenase SerA/LpdA double mutant is unable to utilize glycine as a serine source and lacks detectable GCV enzyme activity	759421	
1.4.1.27	physiological function	in tobacco plants overexpressing the Arabidopsis thaliana H-protein, under controlled environment conditions an increase in biomass is evident. Targeted overexpression of the H-protein using the leaf-specific promoter ST-LS1 has a positive impact on biomass, but higher levels of overexpression of this protein driven by the constitutive CaMV 35S promoter result in a reduction in the growth of the plants. In the constitutive overexpressor plants, carbon allocation between soluble carbohydrates and starch is altered, as is the protein lipoylation of the pyruvate dehydrogenase and 2-oxoglutarate complexes	759926	
1.4.1.27	physiological function	mutations in Gldc result in severe or mild elevations of plasma glycine and model non-ketotic hyperglycinemia. Liver of Gldc-deficient mice accumulates glycine and numerous glycine derivatives, including multiple acylglycines. Levels of dysregulated metabolites increase with age and are normalised by liver-specific rescue of Gldc expression. Brain tissue exhibits increased abundance of glycine, as well as derivatives including guanidinoacetate. Elevation of brain tissue glycine occurs even in the presence of only mildly elevated plasma glycine in mice carrying a missense allele of Gldc. Treatment with benzoate enhances hepatic glycine conjugation thereby lowering plasma and tissue glycine. Administration of glycine conjugation pathway intermediate, cinnamate, similarly achieves normalisation of liver glycine derivatives and circulating glycine	759585	
1.4.1.27	physiological function	structure-based dynamic analysis of the induced release of the lipoate arm of protein H. Four major steps of the release process can be distinguished showing significantly different energy barriers and time scales. Mutations of key residue, Ser67 in protein H, leads to a bidirectional tuning of the release process	759080	
1.4.1.27	physiological function	T-protein knock out parasites do not show any growth defect in asexual, sexual and liver stages. T-protein is dispensable for parasite survival in vertebrate and invertebrate hosts	743266	
1.4.1.27	physiological function	the component T-protein catalyzes the degradation of the protein-bound intermediate (-CH2NH2 moiety of glycine) to a 1-carbon unit and NH3. The reaction is dependent on tetrahydrofolate. T-protein associates with H-protein forming a complex of one molecule each of T-protein and H-protein	759448	
1.4.1.27	physiological function	the glycine cleavage system CGS is highly activated to promote stem cell pluripotency and during somatic cell reprogramming. The expression of glycine dehydrogenase GldC, regulated by Sox2 and Lin28A, facilitates this activation. The activated GCS catabolizes glycine to fuel histone H3K4me3 modification, promoting the expression of pluripotency genes. The activated GCS helps to cleave excess glycine and prevents methylglyoxal accumulation, which stimulates senescence in stem cells and during reprogramming	759700	
1.4.1.27	physiological function	the isolated component P-protein can bind glycine and catalyze glycine decarboxylation but at extremely low rate. The product of glycine decarboxylation is methylamine. Methylamine can bind to P-protein, inhibiting the glycine decarboxylation. P-protein alone can also slightly catalyze the exchange of carboxyl carbon of glycine with CO2 and the exchange obeys a pingpong mechanism	759446	
1.4.1.27	physiological function	the lipoamide dehydrogenase component, cf. EC 1.8.1.4, is an indistinguishable constituent among alpha-keto acid dehydrogenase complexes and the glycine cleavage system in mitochondria in nature, and lipoamide dehydrogenase-mediated transfer of reducing equivalents might regulate alpha-keto acid oxidation as well as glycine oxidation	758695	
1.4.1.27	physiological function	the reversible glycine cleavage system in liver mitochondria involves four enzyme proteins designated as P-protein (a pyridoxal phosphate requiring protein), H-protein (a hydrogen carrier protein), L-protein (exhibiting a lipoamide dehydrogenase activity) and T-protein (a H4-folate requiring protein). All three protein fractions obtained during purification are essential for the overall reactions of glycine cleavage and glycine synthesis, while only P-, L-protein and H-protein are required for the glycine-14CO2 exchange	759438	
1.4.1.27	physiological function	the reversible glycine cleavage system is composed of four protein components named as P-, H-, L-, and T-protein, respectively. P-protein catalyzes the decarboxylation of glycine or its reverse reaction in the presence of H-protein, and T-protein participates in the formation of one carbon unit and ammonia or the reverse reaction	758694