Aspartate semialdehyde dehydrogenase reaction

The next two reactions in the pathway are catalyzed by aspartate semialdehyde dehydrogenase and homoserine dehydrogenase, respectively (Fig. 2). Both enzymes were initially detected in extracts of pea seedlings (Sasa-oka and Inagaki, 1960 Sasaoka, 1961) and subsequently characterized as B stereospecific with respect to hydride transfer from the dihydropyridine ring of NADPH (Davies el al., 1972). Aspartate semialdehyde dehydrogenase has also been detected in extracts of maize shoots, roots, developing kernels,... 

So, the biosynthesis of methionine (Met, M), the first of the essential amino adds to be considered (Scheme 12.13), begins by the conversion of aspartate (Asp, D) to aspartate semialdehyde in the same way glutamate (Glu, E) was converted to glutamate semialdehyde (vide supra. Scheme 12.6). Phosphorylation on the terminal carboxylate of aspartate (Asp, D) by ATP in the presence of aspartate kinase (EC 2.7.2.4) and subsequent reduction of the aspart-4 yl phosphate by NADPH in the presence of aspartate semialdehyde dehydrogenase (EC 1.2.1.11) yields the aspartate semialdehyde. The aspartate semialdehyde is further reduced to homoserine (homoserine oxoreductase, EC 1.1.1.3) and the latter is succinylated by succinyl-CoA with the liberation of coenzyme A (CoA-SH) in the presence of homoserine O-succinyl-transferase (EC 2.3.1.46). Then, reaction with cysteine (Cys, C) in the presence of cystathionine y-synthase (EC 2.5.1.48) produces cystathionine and succinate. In the presence of the pyridoxal phosphate protein cystathionine P-lyase (EC 4.4.1.8), both ammonia and pyruvate are lost from cystathionine and homocysteine is produced. Finally, methylation on sulfur to generate methionine (Met, M) occurs by the donation of the methyl from 5-methyltetrahydrofolate in the presence of methonine synthase (EC 2.1.1.13). 

Aspartyl phosphate is reduced to aspartic-/3-semialdehyde (ASA) by aspartic semialdehyde dehydrogenase. The reaction resembles that catalyzed by triose phosphate dehydrogenase, but specifically requires TPN (III). The equilibrium constant is about 3 X 10 , so that at neutral... 

The reactions catalyzed by aspartokinase (1) and aspartate semialdehyde dehydrogenase (2) are utilized for the synthesis of all pathway products, including threonine. Regulation of aspartokinase activity is, therefore, considered to be of central importance in the overall control of the pathway. Two classes of differentially regulated isozymes of aspartokinase have been isolated from plants. One class is comprised of enzymes subject to feedback inhibition by threonine the other encompasses those inhibited by lysine, or by lysine and 5 -adenosylmethionine. Examples of each class have been isolated from several... 

In E. coli there are three aspartokinases that catalyze the conversion of aspartate to p-aspartyl phosphate. All three catalyze the same reaction, but they have very different regulatory properties, as is indicated in Fig. 24-13. Each enzyme is responsive to a different set of end products. The same is true for the two aspartate semialdehyde reductases which catalyze the third step. Both repression of transcription and feedback inhibition of the enzymes are involved. Two of the aspartokinases of E. coli are parts of bifimctional enzymes, which also contain the homoserine dehydrogenases that are needed to reduce aspartate semialdehyde in the third step. These aspar-tokinase-homoserine dehydrogenases 1 and 11 (Fig. 

Starting from the building block of L-aspartate, the biosynthesis of L-threonine comprises five successive reactions sequencially catalyzed by aspartate kinase, aspartyl semialdehyde dehydrogenase, homoserine dehydrogenase, homoserine kinase and threonine synthase. 

This is accomplished by the action of aspartic jS-semialdehyde dehydrogenase as shown in Fig. 3, reaction 2 lOS). This enzyme catalyzes the reversible reduction of /9-aspartyl phosphate by TPNH to form aqraurtic fi-semialdehyde. The source of the /9-aspartyl phosphate in the experiments of Black and Wright was either the chemically prepared or enzymically formed compound. This enzyme was purified about thirtyfold from brewer s yeast extract by elimination of inert material by heating to 60°, acid pre-... 

The reaction catalyzed by aspartic jS-semialdehyde dehydrogenase is analogous to the one catalyzed by 3-phosphoglyceraldehyde dehydrogenase This similarity is shown by the parallel inhibition of both enzymes by iodoacetate and by the catalysis of an arsenolysis of its acyl phosphate substrate by both enzymes. 

Aspartate kinase [EC 2.T.2.4], also known as asparto-kinase, catalyzes the reaction of aspartate with ATP to produce 4-phosphoaspartate and ADP. The enzyme isolated from E. coli is a multifunctional protein, also exhibiting the ability to catalyze the reaction of homoserine with NAD(P) to produce aspartate 4-semialdehyde and NAD(P)H (that is, the activity of homoserine dehydrogenase, EC 1.1.1.3). 

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