If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
Synonyms: threonine D-lactate catabolism, threonine catabolism
|Superclasses:||Degradation/Utilization/Assimilation → Amino Acids Degradation → Threonine Degradation|
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 188.8.131.52) 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 184.108.40.206) 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 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 220.127.116.11), 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 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 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 [Kim02], 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 threonine degradation II and threonine degradation III (to methylglyoxal)). TDH is is a major route for threonine degradation in E. coli. A minor pathway is shown in threonine degradation IV and an anaerobic pathway is shown in threonine degradation I.
About This Pathway
threonine dehydrogenase (TDH) catalyzes the NAD+-dependent oxidation of threonine to 2-amino-3-oxobutanoate which is typically converted by 2-amino-3-ketobutyrate CoA ligase into glycine and acetyl-CoA (see threonine degradation II). However, it has been shown that 2-amino-3-oxobutanoate can also be non-enzymatically decarboxylated to aminoacetone. In E. coli, a mutant that overproduced TDH utilized threonine as the sole carbon source and excreted glycine and aminoacetone into the medium. Crude extracts of this mutant catalyzed a quantitative conversion of threonine to glycine and aminoacetone [Boylan83].
In E. coli the subsequent metabolism of aminoacetone remains unclear. In eukaryotic cells aminoacetone is oxidized to toxic methylglyoxal by semicarbazide-sensitive, Cu2+-dependent amine oxidases in a reaction yielding methylglyoxal, hydrogen peroxide and ammonia [Ray83, Lyles96, Dutra01]. However, E. coli contains a periplasmic copper-containing amine oxidase encoded by tynA that could hypothetically convert aminoacetone to methylglyoxal as predicted in this pathway. Another possible route for aminoacetone metabolism was suggested by [Kelley85] who characterized an E. coli enzyme that stereospecifically and reversibly catalyzed the reduction of aminoacetone to D-1-amino-2-propanol (see L-1,2-propanediol dehydrogenase / glycerol dehydrogenase). Methylglyoxal is toxic to E. coli [Kim04b], although it can be degraded as shown in the pathway link.
Older literature reporting on the metabolism of aminoacetone in other microorganisms may also be relevant to E. coli. Aminoacetone was first isolated and identified in the supernatant from washed cell suspensions of Staphylococcus aureus incubated with threonine [Elliott60]. Subsequent reports were summarized by [Higgins67] who concluded that a number of microorganisms can metabolize aminoacetone via methylglyoxal. In a species of Arthrobacter, aminoacetone in the growth medium was shown to be oxidatively deaminated to methylglyoxal by a putative amine oxidase [Green68]. The conversion of aminoacetone to methylglyoxal has also been suggested to occur in Serratia marcescens although it was not experimentally demonstrated [Komatsubara78]. In cell-free extracts of a strain of Bacillus subtilis grown on nutrient broth, aminoacetone was formed from threonine and was alternatively transaminated to methylglyoxal or reduced to 1-aminopropan-2-ol [Willetts70]. In threonine-grown Bacillus subtilis, data suggested that aminoacetone was reduced to 1-aminopropan-2-ol by a distinct aminoacetone NADH reductase [Rahhal67, Willetts71]. A Pseudomonas species utilized aminoacetone in a pathway involving its metabolism to L-1-aminopropan-2-ol by L-1-aminopropan-2-ol-NAD(P) oxidoreductase, with subsequent reactions converting the latter compound to propionate [Faulkner74].
Superpathways: superpathway of threonine metabolism
Boylan83: Boylan SA, Dekker EE (1983). "Growth, enzyme levels, and some metabolic properties of an Escherichia coli mutant grown on L-threonine as the sole carbon source." J Bacteriol 156(1);273-80. PMID: 6413491
Dutra01: Dutra F, Knudsen FS, Curi D, Bechara EJ (2001). "Aerobic oxidation of aminoacetone, a threonine catabolite: iron catalysis and coupled iron release from ferritin." Chem Res Toxicol 14(9);1323-9. PMID: 11559049
Faulkner74: Faulkner A, Turner JM (1974). "Microbial metabolism of amino alcohols. Aminoacetone metabolism via 1-aminopropan-2-ol in Pseudomonas sp. N.C.I.B. 8858." Biochem J 138(2);263-76. PMID: 4362743
Kelley85: Kelley JJ, Dekker EE (1985). "Identity of Escherichia coli D-1-amino-2-propanol:NAD+ oxidoreductase with E. coli glycerol dehydrogenase but not with Neisseria gonorrhoeae 1,2-propanediol:NAD+ oxidoreductase." J Bacteriol 1985;162(1);170-5. PMID: 3920199
Kim02: 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
Kim04b: Kim I, Kim E, Yoo S, Shin D, Min B, Song J, Park C (2004). "Ribose utilization with an excess of mutarotase causes cell death due to accumulation of methylglyoxal." J Bacteriol 186(21);7229-35. PMID: 15489434
Lyles96: Lyles GA (1996). "Mammalian plasma and tissue-bound semicarbazide-sensitive amine oxidases: biochemical, pharmacological and toxicological aspects." Int J Biochem Cell Biol 28(3);259-74. PMID: 8920635
Willetts71: Willetts AJ, Turner JM (1971). "Threonine metabolism in a strain of Bacillus subtilis enzymic oxidation of 1-aminopropan-2-ol and aminoacetone." Biochim Biophys Acta 252(1);98-104. PMID: 4334917
Azakami94: Azakami H, Yamashita M, Roh JH, Suzuki H, Kumagai H, Murooka Y (1994). "Nucleotide sequence of the gene for monoamine oxidase (maoA) from Escherichia coli." Journal of Fermentation and Bioengineering 77(3):315-319.
Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554
Chen95: Chen YW, Dekker EE, Somerville RL (1995). "Functional analysis of E. coli threonine dehydrogenase by means of mutant isolation and characterization." Biochim Biophys Acta 1253(2);208-14. PMID: 8519804
Cooper92: Cooper RA, Knowles PF, Brown DE, McGuirl MA, Dooley DM (1992). "Evidence for copper and 3,4,6-trihydroxyphenylalanine quinone cofactors in an amine oxidase from the gram-negative bacterium Escherichia coli K-12." Biochem J 1992;288 ( Pt 2);337-40. PMID: 1334402
Craig90: Craig PA, Dekker EE (1990). "The sulfhydryl content of L-threonine dehydrogenase from Escherichia coli K-12: relation to catalytic activity and Mn2+ activation." Biochim Biophys Acta 1990;1037(1);30-8. PMID: 2104757
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
Epperly89: Epperly BR, Dekker EE (1989). "Inactivation of Escherichia coli L-threonine dehydrogenase by 2,3-butanedione. Evidence for a catalytically essential arginine residue." J Biol Chem 1989;264(31);18296-301. PMID: 2681195
Epperly91: Epperly BR, Dekker EE (1991). "L-threonine dehydrogenase from Escherichia coli. Identification of an active site cysteine residue and metal ion studies." J Biol Chem 1991;266(10);6086-92. PMID: 2007567
Ferrandez97a: Ferrandez A, Prieto MA, Garcia JL, Diaz E (1997). "Molecular characterization of PadA, a phenylacetaldehyde dehydrogenase from Escherichia coli." FEBS Lett 1997;406(1-2);23-7. PMID: 9109378
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