MetaCyc Pathway: glycine biosynthesis I
Inferred from experiment

Enzyme View:

Pathway diagram: glycine biosynthesis I

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: BiosynthesisAmino Acids BiosynthesisProteinogenic Amino Acids BiosynthesisGlycine Biosynthesis

Some taxa known to possess this pathway include : Arabidopsis thaliana col, Escherichia coli K-12 substr. MG1655, Saccharomyces cerevisiae

Expected Taxonomic Range: Bacteria , Eukaryota

General Background

Saccharomyces cerevisiae can biosynthesize glycine via three different pathways.

When the cells are grown with glucose as the carbon source, two alternative pathways operate. In one pathway L-threonine aldolase, encoded by GLY1, produces glycine from L-threonine (which is produced from the glycolytic intermediate oxaloacetate) (see glycine biosynthesis IV). In the other pathway glycine is formed from L-serine (a product of 3-phospho-D-glycerate, another glycolytic intermediate) via two serine hydroxymethyltransferases - a cytosolic enzyme (SHMT2) and a mitochondrial enzyme (SHMT1) (see glycine biosynthesis I). The two isoforms are reported to work in opposite directions, depending on the culture conditions [Kastanos97].

When the cells are grown with a non-fermentable carbon source, such as ethanol and acetate, glycine is produced from glyoxylate, a product of the glyoxylate cycle, by the enzyme alanine--glyoxylate aminotransferase 1 (see glycine biosynthesis III).

About This Pathway

This single reaction pathway, catalyzed by serine hydroxymethyltransferase, is the major pathway for biosynthesis of glycine in Escherichia coli K-12, and the main source for one carbon units, which are stored in the form of 5,10-methylenetetrahydropteroyl mono-L-glutamate.

In Saccharomyces cerevisiae, mitochondrial and cytoplasmic serine hydroxymethyltransferase (SHMT) isozymes are encoded by distinct nuclear genes ( SHM1 and SHM2). As in Escherichia coli, SHMT is the major provider of not only glycine, but also of one-carbon units [Kastanos97].

When yeast was grown on L-serine as the primary one-carbon source, the cytoplasmic isozyme was the main provider of glycine and one-carbon groups for purine synthesis. When grown on glycine, the mitochondrial SHMT was the predominant isozyme catalyzing the synthesis of serine from glycine and one-carbon units. However, when both serine and glycine were present, the mitochondrial SHMT made a significant contribution of one-carbon units, but not glycine, for purine synthesis [Kastanos97].

Superpathways: superpathway of L-serine and glycine biosynthesis I

Variants: glycine biosynthesis II, glycine biosynthesis III, glycine biosynthesis IV

Unification Links: AraCyc:GLYSYN-PWY, EcoCyc:GLYSYN-PWY

Created 08-Jul-1994 by Riley M, Marine Biological Laboratory
Revised 07-Jan-2008 by Caspi R, SRI International


Kastanos97: Kastanos EK, Woldman YY, Appling DR (1997). "Role of mitochondrial and cytoplasmic serine hydroxymethyltransferase isozymes in de novo purine synthesis in Saccharomyces cerevisiae." Biochemistry 36(48);14956-64. PMID: 9398220

Other References Related to Enzymes, Genes, Subpathways, and Substrates of this Pathway

Angelaccio92: Angelaccio S, Pascarella S, Fattori E, Bossa F, Strong W, Schirch V (1992). "Serine hydroxymethyltransferase: origin of substrate specificity." Biochemistry 31(1);155-62. PMID: 1731867

Baggott00: Baggott JE (2000). "Hydrolysis of 5,10-methenyltetrahydrofolate to 5-formyltetrahydrofolate at pH 2.5 to 4.5." Biochemistry 39(47);14647-53. PMID: 11087421

Bairoch93: Bairoch A, Boeckmann B (1993). "The SWISS-PROT protein sequence data bank, recent developments." Nucleic Acids Res. 21:3093-3096. PMID: 8332529

Beckmann97: Beckmann K, Dzuibany C, Biehler K, Fock H, Hell R, Migge A, Becker TW (1997). "Photosynthesis and fluorescence quenching, and the mRNA levels of plastidic glutamine synthetase or of mitochondrial serine hydroxymethyltransferase (SHMT) in the leaves of the wild-type and of the SHMT-deficient stm mutant of Arabidopsis thaliana in relation to the rate of photorespiration." Planta 202(3);379-86. PMID: 9232907

Blank14: Blank D, Wolf L, Ackermann M, Silander OK (2014). "The predictability of molecular evolution during functional innovation." Proc Natl Acad Sci U S A 111(8);3044-9. PMID: 24516157

Cai95: Cai K, Schirch D, Schirch V (1995). "The affinity of pyridoxal 5'-phosphate for folding intermediates of Escherichia coli serine hydroxymethyltransferase." J Biol Chem 270(33);19294-9. PMID: 7642604

Capela01: Capela D, Barloy-Hubler F, Gouzy J, Bothe G, Ampe F, Batut J, Boistard P, Becker A, Boutry M, Cadieu E, Dreano S, Gloux S, Godrie T, Goffeau A, Kahn D, Kiss E, Lelaure V, Masuy D, Pohl T, Portetelle D, Puhler A, Purnelle B, Ramsperger U, Renard C, Thebault P, Vandenbol M, Weidner S, Galibert F (2001). "Analysis of the chromosome sequence of the legume symbiont Sinorhizobium meliloti strain 1021." Proc Natl Acad Sci U S A 98(17);9877-82. PMID: 11481430

Chistoserdova94: Chistoserdova LV, Lidstrom ME (1994). "Genetics of the serine cycle in Methylobacterium extorquens AM1: cloning, sequence, mutation, and physiological effect of glyA, the gene for serine hydroxymethyltransferase." J Bacteriol 176(21);6759-62. PMID: 7961431

Contestabile00: Contestabile R, Angelaccio S, Bossa F, Wright HT, Scarsdale N, Kazanina G, Schirch V (2000). "Role of tyrosine 65 in the mechanism of serine hydroxymethyltransferase." Biochemistry 39(25);7492-500. PMID: 10858298

Delle94: Delle Fratte S, Iurescia S, Angelaccio S, Bossa F, Schirch V (1994). "The function of arginine 363 as the substrate carboxyl-binding site in Escherichia coli serine hydroxymethyltransferase." Eur J Biochem 225(1);395-401. PMID: 7925461

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Fitzpatrick98: Fitzpatrick TB, Malthouse JP (1998). "A substrate-induced change in the stereospecificity of the serine-hydroxymethyltransferase-catalysed exchange of the alpha-protons of amino acids--evidence for a second catalytic site." Eur J Biochem 252(1);113-7. PMID: 9523719

Florio09: Florio R, Chiaraluce R, Consalvi V, Paiardini A, Catacchio B, Bossa F, Contestabile R (2009). "The role of evolutionarily conserved hydrophobic contacts in the quaternary structure stability of Escherichia coli serine hydroxymethyltransferase." FEBS J 276(1);132-43. PMID: 19019081

Florio09a: Florio R, Chiaraluce R, Consalvi V, Paiardini A, Catacchio B, Bossa F, Contestabile R (2009). "Structural stability of the cofactor binding site in Escherichia coli serine hydroxymethyltransferase--the role of evolutionarily conserved hydrophobic contacts." FEBS J 276(24);7319-28. PMID: 19909338

Garrow93: Garrow TA, Brenner AA, Whitehead VM, Chen XN, Duncan RG, Korenberg JR, Shane B (1993). "Cloning of human cDNAs encoding mitochondrial and cytosolic serine hydroxymethyltransferases and chromosomal localization." J Biol Chem 268(16);11910-6. PMID: 8505317

GOA01: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Goyer05: Goyer A, Collakova E, Diaz de la Garza R, Quinlivan EP, Williamson J, Gregory JF, Shachar-Hill Y, Hanson AD (2005). "5-Formyltetrahydrofolate is an inhibitory but well tolerated metabolite in Arabidopsis leaves." J Biol Chem 280(28);26137-42. PMID: 15888445

Herrington13: Herrington MB, Sitaras C (2013). "The influence of CsgD on the expression of genes of folate metabolism and hmp in Escherichia coli K-12." Arch Microbiol 195(8);559-69. PMID: 23824318

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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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