enzymology An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

, an aspartate-semialdehyde dehydrogenase () is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that is very important in the biosynthesis of amino acids in prokaryotes, fungi, and some higher plants. It forms an early branch point in the metabolic pathway forming lysine, methionine, leucine and isoleucine from aspartate. This pathway also produces diaminopimelate which plays an essential role in bacterial cell wall formation. There is particular interest in ASADH as disabling this enzyme proves fatal to the organism giving rise to the possibility of a new class of antibiotics, fungicides, and herbicides aimed at inhibiting it. The enzyme catalyzes the reversible

chemical reaction A chemical reaction is a process that leads to the chemistry, chemical transformation of one set of chemical substances to another. When chemical reactions occur, the atoms are rearranged and the reaction is accompanied by an Gibbs free energy, ...

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

\rightleftharpoons

L-4-aspartyl phosphate + NADPH + H⁺ The 3 substrates of this enzyme are L-aspartate 4-semialdehyde,

phosphate Phosphates are the naturally occurring form of the element phosphorus. In chemistry, a phosphate is an anion, salt, functional group or ester derived from a phosphoric acid. It most commonly means orthophosphate, a derivative of orthop ...

, and NADP⁺, whereas its 3 products are L-4-aspartyl phosphate, NADPH, and H⁺. However, under physiological conditions the reaction runs in the opposite direction. This enzyme belongs to the family of oxidoreductases, specifically those acting on the aldehyde or oxo group of a donor with NAD+ or NADP+ as acceptor. The

systematic name A systematic name is a name given in a systematic way to one unique group, organism, object or chemical substance, out of a specific population or collection. Systematic names are usually part of a nomenclature. A semisystematic name or semitrivi ...

of this enzyme class is L-aspartate-4-semialdehyde:NADP+ oxidoreductase (phosphorylating). Other names in common use include aspartate semialdehyde dehydrogenase, aspartic semialdehyde dehydrogenase, L-aspartate-beta-semialdehyde:NADP+ oxidoreductase, (phosphorylating), aspartic beta-semialdehyde dehydrogenase, and ASA dehydrogenase. This enzyme participates in

glycine Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (G ...

, serine and threonine metabolism and lysine biosynthesis. Aspartate-semialdehyde dehydrogenase may be cis-regulated by an Asd RNA motif found in the

5' UTR The 5′ untranslated region (also known as 5′ UTR, leader sequence, transcript leader, or leader RNA) is the region of a messenger RNA (mRNA) that is directly Upstream and downstream (DNA), upstream from the initiation codon. This region is im ...

of some Asd genes.

Protein families

This domain contains both ''N''-acetyl-glutamine semialdehyde dehydrogenase (AgrC), which is involved in

arginine Arginine is the amino acid with the formula (H2N)(HN)CN(H)(CH2)3CH(NH2)CO2H. The molecule features a guanidinium, guanidino group appended to a standard amino acid framework. At physiological pH, the carboxylic acid is deprotonated (−CO2−) a ...

biosynthesis, and aspartate-semialdehyde dehydrogenase, an enzyme involved in the biosynthesis of various

amino acids Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the Proteinogenic amino acid, 22 α-amino acids incorporated into p ...

from aspartate. It also contains the yeast and

fungal A fungus (: fungi , , , or ; or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as one of the tradit ...

Arg5,6 protein, which is cleaved into the enzymes N-acetyl-gamma-glutamyl-phosphate reductase and acetylglutamate kinase. These are also involved in

biosynthesis Biosynthesis, i.e., chemical synthesis occurring in biological contexts, is a term most often referring to multi-step, enzyme-Catalysis, catalyzed processes where chemical substances absorbed as nutrients (or previously converted through biosynthe ...

. All proteins in this entry contain a dimerisation domain of semialdehyde dehydrogenase.

Structural studies

As of late 2007, 24 structures have been solved for this class of enzymes, with PDB accession codes , , , , , , , , , , , , , , , , , , , , , , , and .

References

* * Boyer, P.D., Lardy, H. and Myrback, K. (Eds.), The Enzymes, 2nd ed., vol. 7, Academic Press, New York, 1963, p. 203-221. EC 1.2.1 NADPH-dependent enzymes Enzymes of known structure {{1.2-enzyme-stub