Alpha-aminoadipate pathway

The α-aminoadipate pathway is a biochemical pathway for the synthesis of the amino acid L-lysine. In the eukaryotes, this pathway is unique to the higher fungi (containing chitin in their cell walls) and the euglenids.[1] It has also been reported from bacteria of the genus Thermus.[2]

The amino acid L-lysine

Pathway overview

Homocitrate is initially synthesised from acetyl-CoA and 2-oxoglutarate by homocitrate synthase. This is then converted to homoaconitate by homoaconitase and then to homoisocitrate by homoisocitrate dehydrogenase. A nitrogen atom is added from glutamate by aminoadipate aminotransferase to form the α-aminoadipate from which this pathway gets its name. This is then reduced by aminoadipate reductase via an acyl-enzyme intermediate to a semialdehyde. Reaction with glutamate by one class of saccharopine dehydrogenase yields saccharopine which is then cleaved by a second saccharopine dehydrogenase to yield lysine and oxoglutarate.[3]

alpha-Aminoadipic acid

α-Aminoadipic acid

Names
IUPAC name 2-aminohexanedioic acid
Identifiers
CAS Number	542-32-5^Y
3D model (JSmol)	Interactive image Interactive image
ChEBI	CHEBI:37024^Y
ChEMBL	ChEMBL433238^Y
ChemSpider	456^Y
MeSH	2-Aminoadipic+Acid
PubChem CID	469
UNII	1K7B1OED4N^Y
InChI InChI=1S/C6H11NO4/c7-4(6(10)11)2-1-3-5(8)9/h4H,1-3,7H2,(H,8,9)(H,10,11)^Y Key: OYIFNHCXNCRBQI-UHFFFAOYSA-N^Y InChI=1/C6H11NO4/c7-4(6(10)11)2-1-3-5(8)9/h4H,1-3,7H2,(H,8,9)(H,10,11) Key: OYIFNHCXNCRBQI-UHFFFAOYAC
SMILES C(CC(C(=O)O)N)CC(=O)O O=C(O)CCCC(N)C(=O)O
Properties
Chemical formula	C6H11NO4
Molar mass	161.156 g/mol
Appearance	Crystalline
Density	1.333 g/mL
Melting point	196 °C (385 °F; 469 K)
Boiling point	364 °C (687 °F; 637 K)
Hazards
Main hazards	Irritant
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N verify (what is ^YN ?)
Infobox references

α-Aminoadipic acid is an intermediate in the α-Aminoadipic acid pathway for the metabolism of lysine and saccharopine. It is synthesised from homoisocitrate by aminoadipate aminotransferase and reduced by aminoadipate reductase to form the semialdehyde.

A 2013 study identified α-Aminoadipic acid (2-aminoadipic acid) as a novel predictor of the development of diabetes and suggested that it is a potential modulator of glucose homeostasis in humans.[4]

See also

• Adipic acid

References

1. Zabriskie TM, Jackson MD (2000). "Lysine biosynthesis and metabolism in fungi". Natural Product Reports. 17 (1): 85–97. doi:10.1039/a801345d. PMID 10714900.
2. Kosuge T, Hoshino T (1999). "The α-aminoadipate pathway for lysine biosynthesis is widely distributed among Thermus strains". Journal of Bioscience and Bioengineering. 88 (6): 672–5. doi:10.1016/S1389-1723(00)87099-1. PMID 16232683.
3. Xu H, Andi B, Qian J, West AH, Cook PF (2006). "The α-aminoadipate pathway for lysine biosynthesis in fungi". Cell Biochemistry and Biophysics. 46 (1): 43–64. doi:10.1385/CBB:46:1:43. PMID 16943623.
4. Wang TJ, Ngo D, Psychogios N, Dejam A, Larson MG, Vasan RS, Ghorbani A, O'Sullivan J, Cheng S, Rhee EP, Sinha S, McCabe E, Fox CS, O'Donnell CJ, Ho JE, Florez JC, Magnusson M, Pierce KA, Souza AL, Yu Y, Carter C, Light PE, Melander O, Clish CB, Gerszten RE (2013). "2-Aminoadipic acid is a biomarker for diabetes risk". J Clin Invest. 123 (10): 4309–4317. doi:10.1172/JCI64801. PMC 3784523. PMID 24091325.