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Escherichia coli K-12 substr. MG1655 Pathway: L-threonine degradation IV
Inferred from experiment

Pathway diagram: L-threonine degradation IV

If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.

Locations of Mapped Genes:

Schematic showing all replicons, marked with selected genes

Genetic Regulation Schematic

Genetic regulation schematic for L-threonine degradation IV

Superclasses: Degradation/Utilization/AssimilationAmino Acids DegradationProteinogenic Amino Acids DegradationL-threonine Degradation

General Background

Microorganisms and mammals share two of the major, initial routes for threonine degradation. In the first route threonine is catabolized by catabolic threonine dehydratase (EC to ammonia and 2-oxobutanoate. A biosynthetic version of this enzyme also occurs (see threonine deaminase) [Umbarger57]. In the second route threonine is catabolized by threonine dehydrogenase (EC to form 2-amino-3-oxobutanoate, which is mainly cleaved by 2-amino-3-ketobutyrate CoA ligase, forming glycine and acetyl-CoA. The 2-amino-3-oxobutanoate can also be spontaneously converted to aminoacetone, which may be further metabolized to methylglyoxal (see L-threonine degradation III (to methylglyoxal)). A third route has been demonstrated in several bacteria and fungi. This route is based on the enzyme low-specificity L-threonine aldolase (EC, which cleaves threonine directly into glycine and acetaldehyde.

Escherichia. coli has been shown to assimilate nitrogen from some (but not all) amino acids, as well as agmatine, γ-aminobutyrate and the polyamines putrescine and spermidine. These nitrogen sources are used to generate glutamate and glutamine, the major intracellular nitrogen donors. Some nitrogen sources, such as aspartate, can generate glutamate by transamination (see aspartate aminotransferase, PLP-dependent). Others, such as proline and arginine, produce glutamate as end products (glutamate generating amino acids) (see proline degradation and L-arginine degradation II (AST pathway)). Other nitrogen sources, such as serine, require ammonia production for glutamate synthesis (ammonia generating amino acids) (see L-serine degradation). Ammonia generation is required for glutamine synthesis (see L-glutamine biosynthesis I).

In E. coli a low intracellular level of ammonia results in low intracellular glutamine and induction of the nitrogen-regulated (Ntr) response that involves response regulators NtrC transcriptional dual regulator and NtrB sensory histidine kinase. The Ntr response functions in ammonia assimilation, nitrogen scavenging and metabolic coordination.

E. coli has three systems that can transport threonine: serine / threonine:Na+ symporter [Kim02b], branched chain amino acid ABC transporter [Robbins73], and serine / threonine:H+ symporter TdcC [Sumantran90]. Although E. coli can use threonine, glycine, or serine as a nitrogen source, efficient serine or threonine utilization requires amino acid supplementation. Leucine supplementation is required for the use of threonine as a nitrogen source in pathways utilizing threonine dehydrogenase (TDH) which is induced by leucine [Potter77] (see L-threonine degradation II and L-threonine degradation III (to methylglyoxal)). TDH is is a major route for threonine degradation in E. coli. A minor pathway is shown in L-threonine degradation IV and an anaerobic pathway is shown in L-threonine degradation I.

Reviews: Reitzer, L. (2005) "Catabolism of Amino Acids and Related Compounds" EcoSal 3.4.7 [ECOSAL] and [Reitzer03]

About This Pathway

Many organisms, both prokaryotic and eukaryotic, possess an L-threonine aldolase that can catalyze the interconversion of threonine and glycine [Morris69, Yamada70, Liu97, Kataoka97, Kataoka97a, Liu98, Liu98a, Joshi06]. Two types of the enzyme have been described, a low-specificity L-threonine aldolase which accepts both L-threonine and L-allo-threonine [Liu97] (see Escherichia coli low-specificity L-threonine aldolase), and an L-allo-threonine aldolase characterized in Aeromonas jandaei [Kataoka97] (see L-allo-threonine aldolase).

Despite the wide distribution of L-threonine aldolase, its physiological significance is uncertain. It is important for the synthesis of cellular glycine in yeast [Monschau97], but not in wild-type E. coli [Liu98a]. In E. coli, if the major glycine biosynthetic pathway is disrupted by a glyA mutation, low-specificity L-threonine aldolase may provide an alternative glycine biosynthetic pathway [Liu98a] (see glycine biosynthesis I). Although purified GlyA was also shown to cleave threonine, it did so at a very slow rate [Schirch85] (see serine hydroxymethyltransferase). Overall, the low-specificity L-threonine aldolase pathway is considered to be a minor pathway of threonine degradation in E. coli.

Review: Reitzer, L. (2005) "Catabolism of Amino Acids and Related Compounds" EcoSal 3.4.7 [ECOSAL]

Superpathways: superpathway of L-threonine metabolism

Variants: L-threonine degradation I, L-threonine degradation II, L-threonine degradation III (to methylglyoxal)

Created 04-Jan-2007 by Caspi R, SRI International
Last-Curated 21-Nov-2011 by Fulcher C, SRI International


ECOSAL: "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

Joshi06: Joshi V, Laubengayer KM, Schauer N, Fernie AR, Jander G (2006). "Two Arabidopsis threonine aldolases are nonredundant and compete with threonine deaminase for a common substrate pool." Plant Cell 18(12);3564-75. PMID: 17172352

Kataoka97: Kataoka M, Wada M, Nishi K, Yamada H, Shimizu S (1997). "Purification and characterization of L-allo-threonine aldolase from Aeromonas jandaei DK-39." FEMS Microbiol Lett 151(2);245-8. PMID: 9228760

Kataoka97a: Kataoka M, Ikemi M, Morikawa T, Miyoshi T, Nishi K, Wada M, Yamada H, Shimizu S (1997). "Isolation and characterization of D-threonine aldolase, a pyridoxal-5'-phosphate-dependent enzyme from Arthrobacter sp. DK-38." Eur J Biochem 248(2);385-93. PMID: 9346293

Kim02b: Kim YM, Ogawa W, Tamai E, Kuroda T, Mizushima T, Tsuchiya T (2002). "Purification, reconstitution, and characterization of Na(+)/serine symporter, SstT, of Escherichia coli." J Biochem (Tokyo) 132(1);71-6. PMID: 12097162

Liu97: Liu JQ, Nagata S, Dairi T, Misono H, Shimizu S, Yamada H (1997). "The GLY1 gene of Saccharomyces cerevisiae encodes a low-specific L-threonine aldolase that catalyzes cleavage of L-allo-threonine and L-threonine to glycine--expression of the gene in Escherichia coli and purification and characterization of the enzyme." Eur J Biochem 245(2);289-93. PMID: 9151955

Liu98: Liu JQ, Ito S, Dairi T, Itoh N, Kataoka M, Shimizu S, Yamada H (1998). "Gene cloning, nucleotide sequencing, and purification and characterization of the low-specificity L-threonine aldolase from Pseudomonas sp. strain NCIMB 10558." Appl Environ Microbiol 64(2);549-54. PMID: 9464392

Liu98a: Liu JQ, Dairi T, Itoh N, Kataoka M, Shimizu S, Yamada H (1998). "Gene cloning, biochemical characterization and physiological role of a thermostable low-specificity L-threonine aldolase from Escherichia coli." Eur J Biochem 1998;255(1);220-6. PMID: 9692922

Monschau97: Monschau N, Stahmann KP, Sahm H, McNeil JB, Bognar AL (1997). "Identification of Saccharomyces cerevisiae GLY1 as a threonine aldolase: a key enzyme in glycine biosynthesis." FEMS Microbiol Lett 150(1);55-60. PMID: 9163906

Morris69: Morris JG (1969). "Utilization of L-threnonine by a pseudomonad: a catabolic role for L-threonine aldolase." Biochem J 115(3);603-5. PMID: 5353532

Potter77: Potter R, Kapoor V, Newman EB (1977). "Role of threonine dehydrogenase in Escherichia coli threonine degradation." J Bacteriol 132(2);385-91. PMID: 334738

Reitzer03: Reitzer L (2003). "Nitrogen assimilation and global regulation in Escherichia coli." Annu Rev Microbiol 57;155-76. PMID: 12730324

Robbins73: Robbins JC, Oxender DL (1973). "Transport systems for alanine, serine, and glycine in Escherichia coli K-12." J Bacteriol 1973;116(1);12-8. PMID: 4583203

Schirch85: Schirch V, Hopkins S, Villar E, Angelaccio S (1985). "Serine hydroxymethyltransferase from Escherichia coli: purification and properties." J Bacteriol 1985;163(1);1-7. PMID: 3891721

Sumantran90: Sumantran VN, Schweizer HP, Datta P (1990). "A novel membrane-associated threonine permease encoded by the tdcC gene of Escherichia coli." J Bacteriol 1990;172(8);4288-94. PMID: 2115866

Umbarger57: Umbarger HE, Brown B (1957). "Threonine deamination in Escherichia coli. II. Evidence for two L-threonine deaminases." J Bacteriol 73(1);105-12. PMID: 13405870

Yamada70: Yamada H, Kumagai H, Nagate T, Yoshida H (1970). "Crystalline threonine aldolase from Candida humicola." Biochem Biophys Res Commun 39(1);53-8. PMID: 5438301

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

Acebron09: Acebron SP, Martin I, del Castillo U, Moro F, Muga A (2009). "DnaK-mediated association of ClpB to protein aggregates. A bichaperone network at the aggregate surface." FEBS Lett 583(18);2991-6. PMID: 19698713

Aristarkhov96: Aristarkhov A, Mikulskis A, Belasco JG, Lin EC (1996). "Translation of the adhE transcript to produce ethanol dehydrogenase requires RNase III cleavage in Escherichia coli." J Bacteriol 178(14);4327-32. PMID: 8763968

BRENDA14: BRENDA team (2014). Imported from BRENDA version existing on Aug 2014.

Burlingame83: Burlingame R, Chapman PJ (1983). "Stereospecificity in meta-fission catabolic pathways." J Bacteriol 155(1);424-6. PMID: 6345511

Chen91: Chen YM, Lin EC (1991). "Regulation of the adhE gene, which encodes ethanol dehydrogenase in Escherichia coli." J Bacteriol 1991;173(24);8009-13. PMID: 1744060

Clark80: Clark DP, Cronan JE (1980). "Acetaldehyde coenzyme A dehydrogenase of Escherichia coli." J Bacteriol 144(1);179-84. PMID: 6998946

Clark89: Clark DP (1989). "The fermentation pathways of Escherichia coli." FEMS Microbiol Rev 1989;5(3);223-34. PMID: 2698228

Contestabile01: Contestabile R, Paiardini A, Pascarella S, di Salvo ML, D'Aguanno S, Bossa F (2001). "l-Threonine aldolase, serine hydroxymethyltransferase and fungal alanine racemase. A subgroup of strictly related enzymes specialized for different functions." Eur J Biochem 268(24);6508-25. PMID: 11737206

Dailly00: Dailly YP, Bunch P, Clark DP (2000). "Comparison of the fermentative alcohol dehydrogenases of Salmonella typhimurium and Escherichia coli." Microbios 103(406);179-96. PMID: 11131810

Dellomonaco11: Dellomonaco C, Clomburg JM, Miller EN, Gonzalez R (2011). "Engineered reversal of the β-oxidation cycle for the synthesis of fuels and chemicals." Nature 476(7360);355-9. PMID: 21832992

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

diSalvo14: di Salvo ML, Remesh SG, Vivoli M, Ghatge MS, Paiardini A, D'Aguanno S, Safo MK, Contestabile R (2014). "On the catalytic mechanism and stereospecificity of Escherichia coli l-threonine aldolase." FEBS J 281(1);129-45. PMID: 24165453

Echave03: Echave P, Tamarit J, Cabiscol E, Ros J (2003). "Novel antioxidant role of alcohol dehydrogenase E from Escherichia coli." J Biol Chem 278(32);30193-8. PMID: 12783863

Ferrandez97a: Ferrandez A, Garcia JL, Diaz E (1997). "Genetic characterization and expression in heterologous hosts of the 3-(3-hydroxyphenyl)propionate catabolic pathway of Escherichia coli K-12." J Bacteriol 1997;179(8);2573-81. PMID: 9098055

Fischer13: Fischer B, Boutserin S, Mazon H, Collin S, Branlant G, Gruez A, Talfournier F (2013). "Catalytic properties of a bacterial acylating acetaldehyde dehydrogenase: evidence for several active oligomeric states and coenzyme A activation upon binding." Chem Biol Interact 202(1-3);70-7. PMID: 23237860

Gaudet10: Gaudet P, Livstone M, Thomas P (2010). "Annotation inferences using phylogenetic trees." PMID: 19578431

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."

Goodlove89: Goodlove PE, Cunningham PR, Parker J, Clark DP (1989). "Cloning and sequence analysis of the fermentative alcohol-dehydrogenase-encoding gene of Escherichia coli." Gene 85(1);209-14. PMID: 2695398

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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