This view shows enzymes only for those organisms listed below, in the list of taxa known to possess the pathway. If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
|Superclasses:||Biosynthesis → Amino Acids Biosynthesis → Proteinogenic Amino Acids Biosynthesis → Glycine Biosynthesis|
Expected Taxonomic Range: Opisthokonta
In eukaryotes glycine can be biosynthesized by the reverse reactions of the mitochondrial glycine cleavage complex (for glycine cleavage pathway detail see MetaCyc pathway glycine cleavage). Glycine biosynthesis by reversal of the glycine cleavage complex reactions has been demonstrated in vivo in the yeast Saccharomyces cerevisiae [Maaheimo01, Pasternack92] and in vitro in Gallus gallus (chicken) [Hiraga72] and Rattus norvegicus (rat) [Motokawa74]. In Saccharomyces cerevisiae, there is evidence for the reversibility of the glycine cleavage complex reactions in both aerobic and anaerobic central metabolism [Maaheimo01].
As shown in the reaction link to EC 18.104.22.168, the glycine produced can be used in serine biosynthesis via glycine hydroxymethyltransferase. Glycine can also be biosynthesized from serine by the reverse of the glycine hydroxymethyltransferase reaction, as shown in MetaCyc pathway glycine biosynthesis I [Schlupen03].
In addition to its use in protein biosynthesis, glycine is used in the biosynthesis of other compounds such as tetrapyrroles and purines, as shown in MetaCyc pathways superpathway of purine nucleotides de novo biosynthesis II and superpathway of purine nucleotides de novo biosynthesis I). Along with serine, glycine is an important donor of one-carbon units via the tetrahydrofolate pathways, as shown in MetaCyc pathways folate polyglutamylation, folate transformations I, N10-formyl-tetrahydrofolate biosynthesis and folate transformations II.
Glycine can also be produced by glyoxylate aminotransferase acting on glyoxylate and alanine (see MetaCyc reaction glyoxylate + L-alanine ↔ glycine + pyruvate) [Zhang03e], glyoxylate and glutamate (see MetaCyc pathway photorespiration), or glyoxylate and serine (see MetaCyc pathway formaldehyde assimilation I (serine pathway)).
In bacteria and fungi, glycine can be biosynthesized from threonine by threonine aldolase (see MetaCyc pathway L-threonine degradation IV).
Subpathways: glycine cleavage
Revised in MetaCyc 02-Feb-2007 by Fulcher CA, SRI International
Imported from MetaCyc 23-Nov-2011 by Altman T, SRI International
Revised in HumanCyc 12-Jun-2013 by Weerasinghe D, SRI International
Imported from HumanCyc 31-Jul-2013 by Weerasinghe D, SRI International
Maaheimo01: Maaheimo H, Fiaux J, Cakar ZP, Bailey JE, Sauer U, Szyperski T (2001). "Central carbon metabolism of Saccharomyces cerevisiae explored by biosynthetic fractional (13)C labeling of common amino acids." Eur J Biochem 268(8);2464-79. PMID: 11298766
Motokawa74: Motokawa Y, Kikuchi G (1974). "Glycine metabolism by rat liver mitochondria. Reconstruction of the reversible glycine cleavage system with partially purified protein components." Arch Biochem Biophys 164(2);624-33. PMID: 4460882
Pasternack92: Pasternack LB, Laude DA, Appling DR (1992). "13C NMR detection of folate-mediated serine and glycine synthesis in vivo in Saccharomyces cerevisiae." Biochemistry 31(37);8713-9. PMID: 1390656
Schlupen03: Schlupen C, Santos MA, Weber U, de Graaf A, Revuelta JL, Stahmann KP (2003). "Disruption of the SHM2 gene, encoding one of two serine hydroxymethyltransferase isoenzymes, reduces the flux from glycine to serine in Ashbya gossypii." Biochem J 369(Pt 2);263-73. PMID: 12350229
Zhang03e: Zhang X, Roe SM, Hou Y, Bartlam M, Rao Z, Pearl LH, Danpure CJ (2003). "Crystal structure of alanine:glyoxylate aminotransferase and the relationship between genotype and enzymatic phenotype in primary hyperoxaluria type 1." J Mol Biol 331(3);643-52. PMID: 12899834
Brautigam05: Brautigam CA, Chuang JL, Tomchick DR, Machius M, Chuang DT (2005). "Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations." J Mol Biol 350(3);543-52. PMID: 15946682
Faure00: Faure M, Bourguignon J, Neuburger M, MacHerel D, Sieker L, Ober R, Kahn R, Cohen-Addad C, Douce R (2000). "Interaction between the lipoamide-containing H-protein and the lipoamide dehydrogenase (L-protein) of the glycine decarboxylase multienzyme system 2. Crystal structures of H- and L-proteins." Eur J Biochem 267(10);2890-8. PMID: 10806386
Fries03: Fries M, Jung HI, Perham RN (2003). "Reaction mechanism of the heterotetrameric (alpha2beta2) E1 component of 2-oxo acid dehydrogenase multienzyme complexes." Biochemistry 42(23);6996-7002. PMID: 12795594
Fujiwara79: Fujiwara K, Okamura K, Motokawa Y (1979). "Hydrogen carrier protein from chicken liver: purification, characterization, and role of its prosthetic group, lipolic acid, in the glycine cleavage reaction." Arch Biochem Biophys 197(2);454-62. PMID: 389161
Fujiwara84: Fujiwara K, Okamura-Ikeda K, Motokawa Y (1984). "Mechanism of the glycine cleavage reaction. Further characterization of the intermediate attached to H-protein and of the reaction catalyzed by T-protein." J Biol Chem 259(17);10664-8. PMID: 6469978
Fujiwara91: Fujiwara K, Okamura-Ikeda K, Hayasaka K, Motokawa Y (1991). "The primary structure of human H-protein of the glycine cleavage system deduced by cDNA cloning." Biochem Biophys Res Commun 176(2);711-6. PMID: 2025283
Gottesmann85: Gottesmann P, Hamm R (1985). "[Lipoamide dehydrogenase, citrate synthase and beta-hydroxyacyl-CoA-dehydrogenase of skeletal muscle. 9. Influence of frozen storage of musculature of sheep, game and poultry on activity and subcellular distribution]." Z Lebensm Unters Forsch 181(5);404-7. PMID: 3840940
Hiraga80: Hiraga K, Kikuchi G (1980). "The mitochondrial glycine cleavage system. Purification and properties of glycine decarboxylase from chicken liver mitochondria." J Biol Chem 255(24);11664-70. PMID: 7440562
Hiraga80a: Hiraga K, Kikuchi G (1980). "The mitochondrial glycine cleavage system. Functional association of glycine decarboxylase and aminomethyl carrier protein." J Biol Chem 255(24);11671-6. PMID: 7440563
Hiraga81: Hiraga K, Kochi H, Hayasaka K, Kikuchi G, Nyhan WL (1981). "Defective glycine cleavage system in nonketotic hyperglycinemia. Occurrence of a less active glycine decarboxylase and an abnormal aminomethyl carrier protein." J Clin Invest 68(2);525-34. PMID: 6790577
Jolley96: Jolley KA, Rapaport E, Hough DW, Danson MJ, Woods WG, Dyall-Smith ML (1996). "Dihydrolipoamide dehydrogenase from the halophilic archaeon Haloferax volcanii: homologous overexpression of the cloned gene." J Bacteriol 178(11);3044-8. PMID: 8655478
Kume91: Kume A, Koyata H, Sakakibara T, Ishiguro Y, Kure S, Hiraga K (1991). "The glycine cleavage system. Molecular cloning of the chicken and human glycine decarboxylase cDNAs and some characteristics involved in the deduced protein structures." J Biol Chem 266(5);3323-9. PMID: 1993704
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