From Wikipedia, the free encyclopedia
Chemical compound
The amino acid L -lysine
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 several species of
yeast , higher
fungi (containing
chitin in their cell walls), and the
euglenids .
[1]
[2]
[3]
[4]
[5] It has also been reported from bacteria of the genus
Thermus
[6] and also in
Pyrococcus horikoshii ,
[7] potentially suggesting a wider distribution than previously thought. This uniqueness of the pathway makes it a potentially interesting target for
antimycotics .
[3]
Pathway overview
Comparison of parts of the diaminopimelate (DAP) pathway (left) and α-aminoadipate (AAA) pathway (right).
This pathway is a part of the glutamate family of amino acid biosynthetic pathways.
[2] The reaction steps in the pathway are similar to the
citric acid cycle .
The first step in the pathway is condensation of
acetyl-CoA with
α-ketoglutarate , which gives
homocitrate . This reaction is catalyzed by
homocitrate synthase . Homocitrate is then converted to
homoaconitate by
homoaconitase and then to
homoisocitrate . This is then
decarboxylated by
homoisocitrate dehydrogenase , which results in
α-ketoadipate . 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.
[2]
Conversion of lysine to α-ketoadipate during degradation of lysine proceeds via the same steps, but in reverse.
[8]
See also
References
^ Zabriskie TM, Jackson MD (2000). "Lysine biosynthesis and metabolism in fungi". Natural Product Reports . 17 (1): 85–97.
doi :
10.1039/a801345d .
PMID
10714900 .
^
a
b
c Xu H, Andi B, Qian J, West AH, Cook PF (2006). "The alpha-aminoadipate pathway for lysine biosynthesis in fungi".
Cell Biochemistry and Biophysics . 46 (1): 43–64.
doi :
10.1385/CBB:46:1:43 .
PMID
16943623 .
S2CID
22370361 .
^
a
b Andi B, West AH, Cook PF (September 2004). "Kinetic mechanism of histidine-tagged homocitrate synthase from Saccharomyces cerevisiae". Biochemistry . 43 (37): 11790–11795.
doi :
10.1021/bi048766p .
PMID
15362863 .
^ Bhattacharjee JK (1985). "alpha-Aminoadipate pathway for the biosynthesis of lysine in lower eukaryotes". Critical Reviews in Microbiology . 12 (2): 131–151.
doi :
10.3109/10408418509104427 .
PMID
3928261 .
^ Bhattacharjee JK, Strassman M (May 1967).
"Accumulation of tricarboxylic acids related to lysine biosynthesis in a yeast mutant" . The Journal of Biological Chemistry . 242 (10): 2542–2546.
doi :
10.1016/S0021-9258(18)95997-1 .
PMID
6026248 .
^ 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 .
^ Nishida, Hiromi; Nishiyama, Makoto; Kobashi, Nobuyuki; Kosuge, Takehide; Hoshino, Takayuki; Yamane, Hisakazu (1999-12-01).
"A Prokaryotic Gene Cluster Involved in Synthesis of Lysine through the Amino Adipate Pathway: A Key to the Evolution of Amino Acid Biosynthesis" . Genome Research . 9 (12): 1175–1183.
doi :
10.1101/gr.9.12.1175 .
ISSN
1088-9051 .
PMID
10613839 .
^ Voet, Donald; Voet, Judith G. (2011). Biochemistry (4. ed.). Hoboken, NJ: Wiley.
ISBN
978-0-470-91745-9 .