If an enzyme name is shown in bold, there is experimental evidence for this enzymatic activity.
Locations of Mapped Genes:
|Superclasses:||Biosynthesis → Amino Acids Biosynthesis → Proteinogenic Amino Acids Biosynthesis → L-isoleucine Biosynthesis|
The pathway of isoleucine biosynthesis from threonine is a five-step pathway that shares its last four steps with the pathway of valine biosynthesis. These entwined pathways are part of the superpathway of branched amino acid biosynthesis, that generates not only isoleucine and valine, but also leucine.
As a consequence of having several of its component enzymes involved in the synthesis of three different amino acids, the pathway of isoleucine biosynthesis is subject to regulation by all three amino acids. The first enzyme in the pathway, L-threonine deaminase, is downregulated by isoleucine and leucine, but is upregulated by valine. The following pathway step, catalyzed by acetohydroxybutanoate synthases (AHAS) I and III, is inhibited by all three amino acids. This apparent paradox of valine stimulation of step one followed by valine inhibition of step two is a product of the preference of AHAS III for processing of the isoleucine precursor 2-oxobutanoate rather than the valine precursor pyruvate. When valine is abundant in the cell, both AHAS enzymes are inhibited, blocking valine production and potentially disrupting isoleucine synthesis as well. However, the stimulation of L-threonine deaminase generates a substantial pool of 2-oxobutanoate. Combined with the high affinity of AHAS III for this compound, this allows the isoleucine synthesis to continue despite inhibition caused by the parallel valine synthesis pathway.
Enteric bacteria such as Escherichia coli K-12 substr. MG1655 and Salmonella enterica enterica serovar Typhimurium have been shown to possess two types of threonine dehydratases - a catabolic enzyme, which is induced by threonine, and a consistitutively- produced biosynthetic enzyme [Umbarger57]. Both enzymes convert threonine to 2-oxobutanoate, but differ in their regulation and expression.
Biosynthetic threonine dehydratases were also described in several soil bacteria [Bell77]. A survey of 75 soil isolates capable of growth on L-threonine revealed a group of three organisms that possessed substantial L-threonine dehydratase activity, to the exclusion of any other threonine-catabolyzing enzyme[Bell72]. The group consisted of Corynebacterium sp. F5 and two Brevibacterium isolates. The enzyme from Corynebacterium sp. F5 was partially purified, and was found to be of the biosynthetic type on the criteria that its formation was consitutive, it was susceptible to inhibition by L-isoleucine, L-valine protected against denaturation and was a positive effector and antagonist of isoleucine, and neither AMP nor ADP acted as effectors [Bell77]. Interestingly, even though the enzyme was of the biosynthetic type, the researchers found that much of the threonine in these organisms was converted to propanoate in a catabolic pathway identical to that described in L-threonine degradation I. Thus, the biosynthetic enzyme was recruited to a catabolic pathway.
Unification Links: EcoCyc:ILEUSYN-PWY
Bell77: Bell SC, Turner JM (1977). "Bacterial catabolism of threonine. Threonine degradation initiated by l-threonine hydrolyase (deaminating) in a species of Corynebacterium." Biochem J 164(3);579-587. PMID: 16743051
LeePeng79: Lee-Peng FC, Hermodson MA, Kohlhaw GB (1979). "Transaminase B from Escherichia coli: quaternary structure, amino-terminal sequence, substrate specificity, and absence of a separate valine-alpha-ketoglutarate activity." J Bacteriol 1979;139(2);339-45. PMID: 378964
Neidhardt96: Neidhardt FC, Curtiss III R, Ingraham JL, Lin ECC, Low Jr KB, Magasanik B, Reznikoff WS, Riley M, Schaechter M, Umbarger HE "Escherichia coli and Salmonella, Cellular and Molecular Biology, Second Edition." American Society for Microbiology, Washington, D.C., 1996.
Ratzkin72: Ratzkin B, Arfin S, Umbarger HE (1972). "Isoleucine and valine metabolism in Escherichia coli. 18. Induction of acetohydroxy acid isomeroreductase." J Bacteriol 112(1);131-41. PMID: 4562389
AlexanderCaudle90: Alexander-Caudle C, Latinwo LM, Jackson JH (1990). "Acetohydroxy acid synthase activity from a mutation at ilvF in Escherichia coli K-12." J Bacteriol 1990;172(6);3060-5. PMID: 2188950
Burns95: Burns DM, Burger MJ, Beacham IR (1995). "Silent genes in bacteria: the previously designated 'cryptic' ilvHI locus of 'Salmonella typhimurium LT2' is active in natural isolates." FEMS Microbiol Lett 131(2);167-72. PMID: 7557326
Chen13b: Chen L, Chen Z, Zheng P, Sun J, Zeng AP (2013). "Study and reengineering of the binding sites and allosteric regulation of biosynthetic threonine deaminase by isoleucine and valine in Escherichia coli." Appl Microbiol Biotechnol 97(7);2939-49. PMID: 22669632
Dailey86a: Dailey FE, Cronan JE (1986). "Acetohydroxy acid synthase I, a required enzyme for isoleucine and valine biosynthesis in Escherichia coli K-12 during growth on acetate as the sole carbon source." J Bacteriol 1986;165(2);453-60. PMID: 3511034
Daniels92: Daniels DL, Plunkett G, Burland V, Blattner FR (1992). "Analysis of the Escherichia coli genome: DNA sequence of the region from 84.5 to 86.5 minutes." Science 1992;257(5071);771-8. PMID: 1379743
Datta87: Datta P, Goss TJ, Omnaas JR, Patil RV (1987). "Covalent structure of biodegradative threonine dehydratase of Escherichia coli: homology with other dehydratases." Proc Natl Acad Sci U S A 1987;84(2);393-7. PMID: 3540965
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
Eisenstein94: Eisenstein E, Yu HD, Schwarz FP (1994). "Cooperative binding of the feedback modifiers isoleucine and valine to biosynthetic threonine deaminase from Escherichia coli." J Biol Chem 269(47);29423-9. PMID: 7961922
Eisenstein95: Eisenstein E (1995). "Allosteric regulation of biosynthetic threonine deaminase from Escherichia coli: effects of isoleucine and valine on active-site ligand binding and catalysis." Arch Biochem Biophys 316(1);311-8. PMID: 7840631
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