2-Amino-3-carboxymuconic semialdehyde

2-Amino-3-carboxymuconic semialdehyde
Skeletal formula of 2-amino-3-carboxymuconic semialdehyde
Ball-and-stick model of the 2-amino-3-carboxymuconic semialdehyde molecule as a zwitterion
Names
Preferred IUPAC name
(2Z)-2-Amino-3-[(1Z)-3-oxoprop-1-en-1-yl]but-2-enedioic acid
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
KEGG
  • InChI=1S/C7H7NO5/c8-5(7(12)13)4(6(10)11)2-1-3-9/h1-3H,8H2,(H,10,11)(H,12,13)/b2-1-,5-4- checkY
    Key: KACPVQQHDVBVFC-OIFXTYEKSA-N checkY
  • C(=CC(=C(C(=O)O)N)C(=O)O)C=O
Properties
C7H7NO5
Molar mass 185.13 g/mol
Density 1.527 g/mL
Boiling point 389 °C (732 °F; 662 K)
Hazards
Flash point 189 °C (372 °F; 462 K)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

2-Amino-3-carboxymuconic semialdehyde[1][2] is an intermediate in the metabolism of tryptophan in the kynurenine pathway. Quinolinic acid is a neurotoxin formed nonenzymatically from 2-amino-3-carboxymuconic semialdehyde in mammalian tissues. 2-Amino-3-carboxymuconic semialdehyde is enzymatically converted to picolinic acid via 2-aminomuconic semialdehyde.

Biosynthesis

The enzyme 3-hydroxyanthranilate 3,4-dioxygenase uses oxygen to cleave the aromatic ring of 3-hydroxyanthranilic acid, giving 2-amino-3-carboxymuconic semialdehyde.[3]

2D representation of the chemical structure of 3-Hydroxyanthranilic acid .
3-Hydroxyanthranilic acid
 
O2
 
Rightward reaction arrow with minor substrate(s) from top left
 
 
 
2D representation of the chemical structure of Q2823201.
2-amino-3-carboxymuconic semialdehyde

Metabolism

The kynurenine pathway of tryptophan catabolism leads to nicotinamide adenine dinucleotide and supplies the nicotinic acid component of that cofactor.[3][4] In this pathway, quinolinic acid is produced spontaneously from the intermediate semialdehyde as its amine cyclises with the aldehyde, losing a molecule of water:[5]

2D representation of the chemical structure of Q2823201.
2-amino-3-carboxymuconic semialdehyde
 
 
H2O
Rightward reaction arrow with minor product(s) to top right
 
 
 
2D representation of the chemical structure of quinolinic acid .
quinolinic acid

Alternatively, 2-amino-3-carboxymuconic semialdehyde can be acted on by the enzyme aminocarboxymuconate-semialdehyde decarboxylase to give 2-aminomuconic semialdehyde, an unstable open-chain precursor of picolinic acid.[4][6][7][8]

2D representation of the chemical structure of Q2823201.
2-Amino-3-carboxymuconic semialdehyde
Enzymic
 
CO2
Rightward reaction arrow with minor product(s) to top right
 
 
 
2D representation of the chemical structure of 2-Aminomuconic semialdehyde .
2-Aminomuconic semialdehyde
Spontaneous
 
H2O
Rightward reaction arrow with minor product(s) to top right
 
 
 
2D representation of the chemical structure of Picolinic acid .
Picolinic acid

References

  1. ^ "UniProt". www.uniprot.org. Retrieved 2022-11-22.
  2. ^ "Human Metabolome Database: Showing metabocard for 2-Amino-3-carboxymuconic acid semialdehyde (HMDB0001330)". hmdb.ca. Retrieved 2022-11-22.
  3. ^ a b Decker, R.H.; Kang, H.H.; Leach, Franklin R.; Henderson, L.M. (1961). "Purification and Properties of 3-Hydroxyanthranilic Acid Oxidase". Journal of Biological Chemistry. 236 (11): 3076–3082. doi:10.1016/S0021-9258(19)76432-1.
  4. ^ a b Savitz, J (25 January 2020). "The kynurenine pathway: a finger in every pie". Molecular Psychiatry. 25 (1): 131–147. doi:10.1038/s41380-019-0414-4. PMC 6790159. PMID 30980044.
  5. ^ Schwarcz, Robert; Bruno, John P.; Muchowski, Paul J.; Wu, Hui-Qiu (2012). "Kynurenines in the mammalian brain: When physiology meets pathology". Nature Reviews Neuroscience. 13 (7): 465–477. doi:10.1038/nrn3257. PMC 3681811. PMID 22678511.
  6. ^ He, Z.; Spain, J. (1999-08-01). "Preparation of 2-aminomuconate from 2-aminophenol by coupled enzymatic dioxygenation and dehydrogenation reactions". Journal of Industrial Microbiology & Biotechnology. 23 (2): 138–142. doi:10.1038/sj.jim.2900705. ISSN 1476-5535. PMID 10510494. S2CID 1091252.
  7. ^ Zeng, Ting; Liang, Yanshan; Chen, Jinyao; Cao, Guodong; Yang, Zhu; Zhao, Xingchen; Tian, Jinglin; Xin, Xiong; Lei, Bo; Cai, Zongwei (2021-09-01). "Urinary metabolic characterization with nephrotoxicity for residents under cadmium exposure". Environment International. 154 106646. Bibcode:2021EnInt.15406646Z. doi:10.1016/j.envint.2021.106646. ISSN 0160-4120. PMID 34049269.
  8. ^ Davis, Ian; Yang, Yu; Wherritt, Daniel; Liu, Aimin (2018). "Reassignment of the human aldehyde dehydrogenase ALDH8A1 (ALDH12) to the kynurenine pathway in tryptophan catabolism". Journal of Biological Chemistry. 293 (25): 9594–9603. doi:10.1074/jbc.RA118.003320. PMC 6016481. PMID 29703752.
allikas: https://en.wikipedia.org/wiki/2-amino-3-carboxymuconic_semialdehyde