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.
Synonyms: 2-aminoadipate pathway
|Superclasses:||Degradation/Utilization/Assimilation → Amino Acids Degradation → Proteinogenic Amino Acids Degradation → L-lysine Degradation|
Expected Taxonomic Range:
Fluorescent pseudomonads such as Pseudomonas putida and Pseudomonas fluorescens can catabolize lysine and other amino acids as a sole carbon and nitrogen source, giving them the ability to grow in the rhizosphere of plants where amino acids are part of the root exudates. These soil bacteria are believed to promote the growth and health of crop plants (in [Revelles05, Revelles04, EspinosaUrgel01]).
Pseudomonas putida can catabolize L-lysine via the 5-aminopentanoate (δ-aminovalerate) (AMV) pathway to glutarate (see MetaCyc pathway L-lysine degradation IV). However, some strains also catabolize D-lysine via a separate, pipecolate pathway shown here. This pathway involves a lysine racemase that converts L-lysine to D-lysine, which is then converted to cyclic, six-carbon intermediates ( [Chang71] and in [Muramatsu05, Revelles05, Chang77]). This pathway is also known as the α-aminoadipate ( L-2-aminoadipate) (AMA) pathway, and some of the enzymes, as well as a transporter, may be encoded on the OCT plasmid ( [Cao93a] and in [Revelles05]).
Two enzymes have been identified as involved in the conversion of D-lysine to 1-piperideine-2-carboxylate in Pseudomonas putida KT2440. One is a D-lysine aminotransferase encoded by amaC (PP3590), and the other is a D-lysine dehydrogenase (or D-lysine oxidase) encoded by amaD (PP3596). Both mutant and biochemical studies suggested that AmaD plays a major role, while AmaC has a minor, as yet undefined role [Revelles07]. Earlier evidence for this conversion derived from induction studies [Chang74], radiolabeling experiments [Miller71], and trapping of 1-piperideine-2-carboxylate as an o-aminobenzaldehyde adduct [Cao93a].
The cyclic intermediate substrates 1-piperideine-2-carboxylate and Δ1-piperidine-6-carboxylate ( 1-piperideine 6-carboxylate) are isomers, their nitrogen atoms deriving from the epsilon and alpha nitrogens of lysine, respectively [Broquist91]. They also exist in equilibrium with their open chain forms, 2-keto-6-aminocaproate and (S)-2-amino-6-oxohexanoate (α-aminoadipate δ-semialdehyde), respectively [Broquist91, Calvert66, Rodwell71, IJlst00].
α-Ketoadipate ( 2-oxoadipate) may be converted to glutarate by an uncharacterized ketoadipate decarboxylase [Revelles05, Revelles07]. Although the conversion of glutarate to glutaryl-CoA is also uncharacterized, glutaryl-CoA may be degraded as shown by the pathway link [Numa64], or via 2-hydroxyglutarate (α-hydroxyglutarate) and 2-oxoglutarate (α-ketoglutarate) as suggested in [Cao93a] and [Perfetti72].
L-lysine catabolism in Pseudomonas varies as to species and strain. Pseudomonas aeruginosa does not use the δ-aminovalerate (AMV) pathway. It was proposed to catabolizes L-lysine via decarboxylation to cadaverine (in [Revelles05]) (see MetaCyc pathway L-lysine degradation I).
Fungi and mammals have also been shown to degrade D-lysine or L-lysine to L-pipecolate. In Rhizoctonia leguminicola, L-pipecolate formed from L-lysine is a biosynthetic precursor of indolizidine alkaloids. In mammals, the predominant pathway for L-lysine degradation is via L-saccharopine (see MetaCyc pathway L-lysine degradation XI (mammalian)). However, the pipecolate pathway via D-lysine or L-lysine is predominant in mammalian brain ( [Chang76] in [IJlst00] and reviewed in [Broquist91]). More recently though, the existence of this pathway has been questioned in studies using L-[α-15N]lysine or L-[ε-15N]lysine in human fibroblasts [Struys10].
Superpathways: superpathway of L-lysine degradation
Variants: L-lysine degradation I, L-lysine degradation II (L-pipecolate pathway), L-lysine degradation III, L-lysine degradation IV, L-lysine degradation VI, L-lysine degradation VII, L-lysine degradation VIII, L-lysine degradation IX, L-lysine degradation X, L-lysine degradation XI (mammalian), L-lysine fermentation to acetate and butanoate
Calvert66: Calvert AF, Rodwell VW (1966). "Metabolism of pipecolic acid in a Pseudomonas species. 3. L-alpha-aminoadipate delta-semialdehyde:nicotinamide adenine dinucleotide oxidoreductase." J Biol Chem 241(2);409-14. PMID: 4285660
Chang77: Chang YF, Adams E (1977). "Factors influencing growth on L-lysine by Pseudomonas. Regulation of terminal enzymes in the delta-aminovalerate pathway and growth stimulation by alpha ketoglutarate." J Biol Chem 252(22);7987-91. PMID: 914858
EspinosaUrgel01: Espinosa-Urgel M, Ramos JL (2001). "Expression of a Pseudomonas putida aminotransferase involved in lysine catabolism is induced in the rhizosphere." Appl Environ Microbiol 67(11);5219-24. PMID: 11679348
Muramatsu05: Muramatsu H, Mihara H, Kakutani R, Yasuda M, Ueda M, Kurihara T, Esaki N (2005). "The putative malate/lactate dehydrogenase from Pseudomonas putida is an NADPH-dependent delta1-piperideine-2-carboxylate/delta1-pyrroline-2-carboxylate reductase involved in the catabolism of D-lysine and D-proline." J Biol Chem 280(7);5329-35. PMID: 15561717
Revelles04: Revelles O, Espinosa-Urgel M, Molin S, Ramos JL (2004). "The davDT operon of Pseudomonas putida, involved in lysine catabolism, is induced in response to the pathway intermediate delta-aminovaleric acid." J Bacteriol 186(11);3439-46. PMID: 15150230
Revelles05: Revelles O, Espinosa-Urgel M, Fuhrer T, Sauer U, Ramos JL (2005). "Multiple and interconnected pathways for L-lysine catabolism in Pseudomonas putida KT2440." J Bacteriol 187(21);7500-10. PMID: 16237033
Struys10: Struys EA, Jakobs C (2010). "Metabolism of lysine in alpha-aminoadipic semialdehyde dehydrogenase-deficient fibroblasts: evidence for an alternative pathway of pipecolic acid formation." FEBS Lett 584(1);181-6. PMID: 19932104
deLa97: de La Fuente JL, Rumbero A, Martin JF, Liras P (1997). "Delta-1-piperideine-6-carboxylate dehydrogenase, a new enzyme that forms alpha-aminoadipate in Streptomyces clavuligerus and other cephamycin C-producing actinomycetes." Biochem J 327 ( Pt 1);59-64. PMID: 9355735
Fujii00: Fujii T, Narita T, Agematu H, Agata N, Isshiki K (2000). "Cloning and characterization of pcd encoding delta'-piperideine-6-carboxylate dehydrogenase from flavobacterium lutescens IFO3084." J Biochem (Tokyo) 128(6);975-82. PMID: 11098140
Fujii00a: Fujii T, Narita T, Agematu H, Agata N, Isshiki K (2000). "Characterization of L-lysine 6-aminotransferase and its structural gene from Flavobacterium lutescens IFO3084." J Biochem (Tokyo) 128(3);391-7. PMID: 10965037
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
Goto05: Goto M, Muramatsu H, Mihara H, Kurihara T, Esaki N, Omi R, Miyahara I, Hirotsu K (2005). "Crystal structures of Delta1-piperideine-2-carboxylate/Delta1-pyrroline-2-carboxylate reductase belonging to a new family of NAD(P)H-dependent oxidoreductases: conformational change, substrate recognition, and stereochemistry of the reaction." J Biol Chem 280(49);40875-84. PMID: 16192274
Hallen11: Hallen A, Cooper AJ, Jamie JF, Haynes PA, Willows RD (2011). "Mammalian forebrain ketimine reductase identified as μ-crystallin; potential regulation by thyroid hormones." J Neurochem 118(3);379-87. PMID: 21332720
Marlaire13: Marlaire S, Van Schaftingen E, Veiga-da-Cunha M (2013). "C7orf10 encodes succinate-hydroxymethylglutarate CoA-transferase, the enzyme that converts glutarate to glutaryl-CoA." J Inherit Metab Dis. PMID: 23893049
Mills06: Mills PB, Struys E, Jakobs C, Plecko B, Baxter P, Baumgartner M, Willemsen MA, Omran H, Tacke U, Uhlenberg B, Weschke B, Clayton PT (2006). "Mutations in antiquitin in individuals with pyridoxine-dependent seizures." Nat Med 12(3);307-9. PMID: 16491085
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
Soda68: Soda K, Misono H, Yamamoto T (1968). "L-Lysine:alpha-ketoglutarate aminotransferase. I. Identification of a product, delta-1-piperideine-6-carboxylic acid." Biochemistry 7(11);4102-9. PMID: 5722275
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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