L-Aspartic-4-semialdehyde

L-Aspartic-4-semialdehyde
Names
	IUPAC name L-Aspart-4-al
	Systematic IUPAC name (2S)-2-Amino-4-oxobutanoic acid
	Other names L-Aspartic-β-semialdehyde
Identifiers
CAS Number	2338-03-6 ;
3D model (JSmol)	Interactive image; Interactive image;
ChEBI	CHEBI:18051;
ChemSpider	388372;
KEGG	C00441;
PubChem CID	439235;
UNII	NM79MG686B ;
CompTox Dashboard (EPA)	DTXSID201336656 DTXSID10934160, DTXSID201336656 ;
	InChI InChI=1S/C4H7NO3/c5-3(1-2-6)4(7)8/h2-3H,1,5H2,(H,7,8)/t3-/m0/s1 Key: HOSWPDPVFBCLSY-VKHMYHEASA-N;
	SMILES C(C=O)C(C(=O)O)N; C(C=O)[C@@H](C(=O)O)N;
Properties
Chemical formula	C4H7NO3
Molar mass	117.104 g·mol−1
Appearance	Solid
	Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa). Infobox references

L-Aspartic-4-semialdehyde is an α-amino acid derivative of aspartate. It is an important intermediate in the aspartate pathway, which is a metabolic pathway present in bacteria and plants. The aspartate pathway leads to the biosynthesis of a variety of amino acids from aspartate, including lysine, methionine, and threonine.^[1]

Aspartate pathway

The aspartate pathway is an amino acid metabolic pathway present in bacteria and plants that deal with converting aspartate to other amino acids through a series of reactions and intermediates. L-Aspartate-4-semialdehyde serves as one of the first intermediates in the pathway and as an important step of differentiation in the pathway.^[2]

L-Aspartate-4-semialdehyde is synthesized by the enzyme aspartate semialdehyde dehydrogenase, which catalyzes the following reversible chemical reaction:

L-4-Aspartyl phosphate + NADPH + H⁺

\rightleftharpoons

L-aspartate-4-semialdehyde + NADP⁺ + phosphate

Once L-aspartate-4-semialdehyde is synthesized, the molecule can then progress down a number of pathways. One possible pathway requires L-aspartate-4-semialdehyde to undergo a reaction catalyzed by the enzyme dihydrodipicolinate synthase in order to form the molecule dihydrodipicolinate. This reversible chemical reaction is shown below:^[3]

L-Aspartate-4-semialdehyde + pyruvate

\rightleftharpoons

dihydrodipicolinate + H₂O

Once dihydrodipicolinate is synthesized, it can continue down the metabolic pathway leading to the synthesis of lysine.^[4] Other than the lysine biosynthetic pathway, L-aspartate-4-semialdehyde can also undergo a reversible reaction catalyzed by the enzyme homoserine dehydrogenase. This reaction, which turns L-aspartate-4-semialdehyde into homoserine is shown below:^[5]

L-Aspartate-4-semialdehyde + NAD(P)H + H⁺

\rightleftharpoons

homoserine + NAD(P)⁺

Homoserine represents another branch in the aspartate pathway, as it can progress down one of two pathways to eventually become one of two amino acids: threonine or methionine. This aspartate pathway is present in plants and bacteria, allowing them to synthesize lysine, methionine, and threonine. This pathway is not present in humans or other animals, however. The lack of this pathway means that humans need to take in these amino acids through their diet, which is why they are called essential amino acids.^[6]^[7]

References

^ Viola, Ronald E. (2001). "The Central Enzymes of the Aspartate Family of Amino Acid Biosynthesis". Accounts of Chemical Research. 34 (5): 339–349. doi:10.1021/ar000057q. PMID 11352712.
^ Thangavelu, B.; Bhansali, P.; Viola, R.E. (2015-10-15). "Elaboration of a fragment library hit produces potent and selective aspartate semialdehyde dehydrogenase inhibitors". Bioorganic & Medicinal Chemistry. 23 (20): 6622–6631. doi:10.1016/j.bmc.2015.09.017. PMC 4601562. PMID 26404410.
^ Mazelis, M.; Whatley, F.R.; Whatley, J. (December 1977). "The enzymology of lysine biosynthesis in higher plants. The occurrence, characterization and some regulatory properties of dihydrodipicolinate synthase". FEBS Letters. 84 (2): 236–240. doi:10.1016/0014-5793(77)80696-0. PMID 598503. S2CID 11088733.
^ Viola, R.E.; Faehnle, C.R.; Blanco, J.; Moore, R.A.; Liu, X.; Arachea, B.T.; Pavlovsky, A.G. (2010-12-22). "The Catalytic Machinery of a Key Enzyme in Amino Acid Biosynthesis". Journal of Amino Acids. 2011: 352–538. doi:10.4061/2011/352538. PMC 3276109. PMID 22332000.
^ Thomas, D.; Barbey, R.; Surdin-Kerjan, Y. (June 1993). "Evolutionary relationships between yeast and bacterial homoserine dehydrogenases". FEBS Letters. 323 (3): 289–293. doi:10.1016/0014-5793(93)81359-8. PMID 8500624. S2CID 23964791.
^ Viola, R.E.; Faehnle, C.R.; Blanco, J.; Moore, R.A.; Liu, X.; Arachea, B.T.; Pavlovsky, A.G. (2010-12-22). "The Catalytic Machinery of a Key Enzyme in Amino Acid Biosynthesis". Journal of Amino Acids. 2011: 352–538. doi:10.4061/2011/352538. PMC 3276109. PMID 22332000.
^ Berg, Jeremy M.; Tymoczko, John L.; Gatto, Gergory J. Jr.; Stryer, Lubert (2015). Biochemistry. New York, NY: W.H. Freeman and Company. p. 719. ISBN 978-1-4641-2610-9.

[1] Viola, Ronald E. (2001). "The Central Enzymes of the Aspartate Family of Amino Acid Biosynthesis". Accounts of Chemical Research. 34 (5): 339–349. doi:10.1021/ar000057q. PMID 11352712.

[2] Thangavelu, B.; Bhansali, P.; Viola, R.E. (2015-10-15). "Elaboration of a fragment library hit produces potent and selective aspartate semialdehyde dehydrogenase inhibitors". Bioorganic & Medicinal Chemistry. 23 (20): 6622–6631. doi:10.1016/j.bmc.2015.09.017. PMC 4601562. PMID 26404410.

[3] Mazelis, M.; Whatley, F.R.; Whatley, J. (December 1977). "The enzymology of lysine biosynthesis in higher plants. The occurrence, characterization and some regulatory properties of dihydrodipicolinate synthase". FEBS Letters. 84 (2): 236–240. doi:10.1016/0014-5793(77)80696-0. PMID 598503. S2CID 11088733.

[4] Viola, R.E.; Faehnle, C.R.; Blanco, J.; Moore, R.A.; Liu, X.; Arachea, B.T.; Pavlovsky, A.G. (2010-12-22). "The Catalytic Machinery of a Key Enzyme in Amino Acid Biosynthesis". Journal of Amino Acids. 2011: 352–538. doi:10.4061/2011/352538. PMC 3276109. PMID 22332000.

[5] Thomas, D.; Barbey, R.; Surdin-Kerjan, Y. (June 1993). "Evolutionary relationships between yeast and bacterial homoserine dehydrogenases". FEBS Letters. 323 (3): 289–293. doi:10.1016/0014-5793(93)81359-8. PMID 8500624. S2CID 23964791.

[6] Viola, R.E.; Faehnle, C.R.; Blanco, J.; Moore, R.A.; Liu, X.; Arachea, B.T.; Pavlovsky, A.G. (2010-12-22). "The Catalytic Machinery of a Key Enzyme in Amino Acid Biosynthesis". Journal of Amino Acids. 2011: 352–538. doi:10.4061/2011/352538. PMC 3276109. PMID 22332000.

[7] Berg, Jeremy M.; Tymoczko, John L.; Gatto, Gergory J. Jr.; Stryer, Lubert (2015). Biochemistry. New York, NY: W.H. Freeman and Company. p. 719. ISBN 978-1-4641-2610-9.

[1]

[2]

[3]

[4]

[5]

[6]

[7]