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MetaCyc Pathway: lysine biosynthesis IV

Enzyme View:

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 Individual Amino Acids Biosynthesis Lysine Biosynthesis

Some taxa known to possess this pathway include ? : Euglena gracilis , Saccharomyces cerevisiae

Expected Taxonomic Range: Euglenozoa , Fungi

Summary:
General Background

Six pathways are now recognized in bacteria, most algae, fungi and higher plants for the biosynthesis of lysine. They are divided into two groups - the diaminopimelate (DAP) pathways, and the L-2-aminoadipate pathways.

In the pathways that belong to the DAP group, lysine is produced from aspartate (along with methionine, threonine and isoleucine). All of the DAP group pathways share the upper segments, which include the four steps required for conversion of L-aspartate to (S)-2,3,4,5-tetrahydrodipicolinate. They also share the last step, which is the conversion of the intermediate meso-diaminopimelate (D,L-DAP, or meso-DAP) to lysine. However, these pathways differ in the routes leading from (S)-2,3,4,5-tetrahydrodipicolinate to meso-diaminopimelate. The four variations include:

(I) the succinylase variant (see lysine biosynthesis I), which involves succinylated intermediates. In this route (S)-2,3,4,5-tetrahydrodipicolinate is coverted to meso-diaminopimelate in four enzymatic steps.

(II) the acetylase variant (see lysine biosynthesis II), which involves acetylated intermediates. This route also involves four enzymatic steps for the conversion of (S)-2,3,4,5-tetrahydrodipicolinate to meso-diaminopimelate.

(III) the dehydrogenase variant (see lysine biosynthesis III), in which (S)-2,3,4,5-tetrahydrodipicolinate is converted to meso-diaminopimelate in a single enzymatic step.

(IV) the diaminopimelate-aminotransferase variant (see lysine biosynthesis VI), in which (S)-2,3,4,5-tetrahydrodipicolinate is converted to meso-diaminopimelate in two steps.

In addition to lysine, all of the pathways in this group also produce meso-diaminopimelate, which is an important metabolite on its own (for example, as a constituent of bacterial cell wall peptidoglycan).

The two other pathways belong to the L-2-aminoadipate group. They are found in organisms that have no requirement for meso-diaminopimelate, as it is not a component of their cell walls. These pathways also share the first segments, leading to the synthesis of the intermediate L-2-aminoadipate (α-aminoadipate). However, in yeast and fungi, as well as Euglena, the pathway continues with the key enzyme α aminoadipate reductase, leading to the intermediate L-saccharopine (see lysine biosynthesis IV), while in prokaryotes the pathway continues in a path similar to bacterial arginine biosynthesis (see lysine biosynthesis V).

Most of the bacteria that have been investigated in detail appear to utilize only one of these pathways [Schrumpf91]. A few exceptions include Paenibacillus macerans, in which variants (II) and (III) seem to coexist [Bartlett85], and Corynebacterium glutamicum, in which variant (I) and (III) coexist [Schrumpf91].

Lysine is one of the 10 essential amino acids that mammals are unable to synthesize, and must therefore acquire in their diets.

About This Pathway

S. cerevisiae synthesizes the essential amino acid L-lysine via the L-α-aminoadipate pathway instead of the diaminopmelate pathway [Zabriskie00]. While some bacteria and archaebacteria synthesize lysine via a similar α-aminoadipate pathway (see lysine biosynthesis V), this particular variation is unique to yeast and fungi [Nishida00].

Intermediates in this pathway are often incoporated into secondary metabolites. For example, it has been well- documented that α-aminoadipate is required for penicillin production [Zabriskie00].

Regulation of the lysine biosynthetic pathway in S. cerevisiae is an interaction between general amino acid control (via Gcn4p) [Hinnebusch92], feedback inhibition of homocitrate synthase activity by lysine [Feller99], and induction of Lys14p by α-aminoadipate semialdehyde [ElAlami00].

Variants: lysine biosynthesis I , lysine biosynthesis II , lysine biosynthesis III , lysine biosynthesis V , lysine biosynthesis VI

Credits:
Created 21-Dec-2004 by Hong E , Saccharomyces Genome Database
Revised 03-Apr-2006 by Caspi R , SRI International


References

Bartlett85: Bartlett, A. T. M., Whilte, P. J. (1985). "Species of Bacillus that make a vegetative peptidoglycan containing lysine lack diaminopimelate epimerase but have diaminopimelate dehydrogenase." J. Gen. Microbiol. 131:2145-2152.

ElAlami00: El-Alami M, Feller A, Pierard A, Dubois E (2000). "Characterisation of a tripartite nuclear localisation sequence in the regulatory protein Lys14 of Saccharomyces cerevisiae." Curr Genet 38(2);78-86. PMID: 10975256

Feller99: Feller A, Ramos F, Pierard A, Dubois E (1999). "In Saccharomyces cerevisae, feedback inhibition of homocitrate synthase isoenzymes by lysine modulates the activation of LYS gene expression by Lys14p." Eur J Biochem 261(1);163-70. PMID: 10103047

Hinnebusch92: Hinnebusch, A (1992). "General and pathway-specific regulatory mechanisms controlling the synthesis of amino acid biosynthetic enzymes in Saccharomyces cerevisiae." The Molecular and Cellular Biology of the yeast Saccharomyces: Gene Expression, Vol 2, pp. 319-414.

Nishida00: Nishida H, Nishiyama M (2000). "What is characteristic of fungal lysine synthesis through the alpha-aminoadipate pathway?." J Mol Evol 51(3);299-302. PMID: 11029074

Schrumpf91: Schrumpf B, Schwarzer A, Kalinowski J, Puhler A, Eggeling L, Sahm H (1991). "A functionally split pathway for lysine synthesis in Corynebacterium glutamicium." J Bacteriol 173(14);4510-6. PMID: 1906065

Zabriskie00: Zabriskie TM, Jackson MD (2000). "Lysine biosynthesis and metabolism in fungi." Nat Prod Rep 17(1);85-97. PMID: 10714900

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

Allen94: Allen RM, Chatterjee R, Madden MS, Ludden PW, Shah VK (1994). "Biosynthesis of the iron-molybdenum cofactor of nitrogenase." Crit Rev Biotechnol 1994;14(3);225-49. PMID: 7954845

Drevland08: Drevland RM, Jia Y, Palmer DR, Graham DE (2008). "Methanogen homoaconitase catalyzes both hydrolyase reactions in coenzyme B biosynthesis." J Biol Chem 283(43);28888-96. PMID: 18765671

Goh02: Goh DL, Patel A, Thomas GH, Salomons GS, Schor DS, Jakobs C, Geraghty MT (2002). "Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT)." Mol Genet Metab 76(3);172-80. PMID: 12126930

Han08: Han Q, Robinson H, Li J (2008). "Crystal structure of human kynurenine aminotransferase II." J Biol Chem 283(6);3567-73. PMID: 18056995

Hoover88: Hoover TR, Imperial J, Liang JH, Ludden PW, Shah VK (1988). "Dinitrogenase with altered substrate specificity results from the use of homocitrate analogues for in vitro synthesis of the iron-molybdenum cofactor." Biochemistry 1988;27(10);3647-52. PMID: 3044446

Hoover89: Hoover TR, Imperial J, Ludden PW, Shah VK (1989). "Homocitrate is a component of the iron-molybdenum cofactor of nitrogenase." Biochemistry 1989;28(7);2768-71. PMID: 2663059

Howell00: Howell DM, Graupner M, Xu H, White RH (2000). "Identification of enzymes homologous to isocitrate dehydrogenase that are involved in coenzyme B and leucine biosynthesis in methanoarchaea." J Bacteriol 2000;182(17);5013-6. PMID: 10940051

Howell98: Howell DM, Harich K, Xu H, White RH (1998). "Alpha-keto acid chain elongation reactions involved in the biosynthesis of coenzyme B (7-mercaptoheptanoyl threonine phosphate) in methanogenic Archaea." Biochemistry 1998;37(28);10108-17. PMID: 9665716

Jia06: Jia Y, Tomita T, Yamauchi K, Nishiyama M, Palmer DR (2006). "Kinetics and product analysis of the reaction catalysed by recombinant homoaconitase from Thermus thermophilus." Biochem J 396(3);479-85. PMID: 16524361

Jones66: Jones EE, Broquist HP (1966). "Saccharopine, an intermediate of the aminoadipic acid pathway of lysine biosynthesis. 3. Aminoadipic semialdehyde-glutamate reductase." J Biol Chem 241(14);3430-4. PMID: 4380448

Kobashi99: Kobashi N, Nishiyama M, Tanokura M (1999). "Aspartate kinase-independent lysine synthesis in an extremely thermophilic bacterium, Thermus thermophilus: lysine is synthesized via alpha-aminoadipic acid not via diaminopimelic acid." J Bacteriol 181(6);1713-8. PMID: 10074061

Kosuge98: Kosuge T, Hoshino T (1998). "Lysine is synthesized through the alpha-aminoadipate pathway in Thermus thermophilus." FEMS Microbiol Lett 169(2);361-7. PMID: 9868782

Latendresse13: Latendresse M. (2013). "Computing Gibbs Free Energy of Compounds and Reactions in MetaCyc."

Liang90: Liang J, Madden M, Shah VK, Burris RH (1990). "Citrate substitutes for homocitrate in nitrogenase of a nifV mutant of Klebsiella pneumoniae." Biochemistry 1990;29(37);8577-81. PMID: 2271541

Lombo04: Lombo T, Takaya N, Miyazaki J, Gotoh K, Nishiyama M, Kosuge T, Nakamura A, Hoshino T (2004). "Functional analysis of the small subunit of the putative homoaconitase from Pyrococcus horikoshii in the Thermus lysine biosynthetic pathway." FEMS Microbiol Lett 233(2);315-24. PMID: 15063502

Miyazaki03: Miyazaki J, Kobashi N, Nishiyama M, Yamane H (2003). "Characterization of homoisocitrate dehydrogenase involved in lysine biosynthesis of an extremely thermophilic bacterium, Thermus thermophilus HB27, and evolutionary implication of beta-decarboxylating dehydrogenase." J Biol Chem 278(3);1864-71. PMID: 12427751

Miyazaki04: Miyazaki T, Miyazaki J, Yamane H, Nishiyama M (2004). "alpha-Aminoadipate aminotransferase from an extremely thermophilic bacterium, Thermus thermophilus." Microbiology 150(Pt 7);2327-34. PMID: 15256574

Rubio06: Rubio S, Larson TR, Gonzalez-Guzman M, Alejandro S, Graham IA, Serrano R, Rodriguez PL (2006). "An Arabidopsis mutant impaired in coenzyme A biosynthesis is sugar dependent for seedling establishment." Plant Physiol 140(3);830-43. PMID: 16415216

Takeuchi83: Takeuchi F, Otsuka H, Shibata Y (1983). "Purification, characterization and identification of rat liver mitochondrial kynurenine aminotransferase with alpha-aminoadipate aminotransferase." Biochim Biophys Acta 743(3);323-30. PMID: 6830814

Tobes77: Tobes MC, Mason M (1977). "Alpha-Aminoadipate aminotransferase and kynurenine aminotransferase. Purification, characterization, and further evidence for identity." J Biol Chem 252(13);4591-9. PMID: 873907

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Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Thu Dec 18, 2014, BIOCYC14A.