3-Aspartate semialdehyde

Orthophosphate as substrate or product, ACETATE KINASE (PYROPHOSPHATE) ACETYL-CoA CARBOXYLASE ACID PHOSPHATASE ACTOMYOSIN ATPase ACYL PHOSPHATASE ASPARTATE-SEMIALDEHYDE DEHYDROGENASE ATPases... 

Zhang, W.W. Jiang, W.H. Zhao, G.P. Yang, Y.L. Chiao, J.S. Expression in Escherichia coli, purification and kinetic analysis of the aspartokinase and aspartate semialdehyde dehydrogenase from the rifamycin SV-producing Amycolatopsis mediterranei U32. Appl. Microbiol. Biotechnol., 54, 52-58 (2000)... 

In the best-documented example of the formation of lysine, the product is formed from aspartate which reacts via aspartylphosphate and aspartate semialdehyde to lysine. The wild type of Brevibacterium lactofermentum does not produce any lysine. With the following steps the yield could be increased to 50 g IT1 ... 

FIGURE 3.4 The common pathway of the aspartate-derived amino acids in Corynebacteria. The mnemonic of the genes involved are shown in parentheses below the enzymes responsible for each step. Dotted lines indicate multiple enzymatic steps, and 16 is L-aspartic acid, 17 is L-aspartyl phosphate, 18 is L-aspartate semialdehyde, 19 is L-lysine, 20 is L-homoserine, 21 is L-isoleucine, 22 is L-threonine, and 23 is L-methionine. 

Overproduction of E (isoleucine) inhibits enzyme E6 (threonine deaminase), and the consequent rise of D (threonine) reduces the rate of production of C (homoserine) via enzyme E3 (homoserine dehydrogenase). The concentration of B (aspartate semialdehyde) rises, and this in turn inhibits Ej (aspartokinase). It is therefore obvious why the control system is called a negative feedback network, or sequential feedback system. 

The fluoromethylene and difluoromethylene linkages have also been incorporated into an aspartyl phosphate, providing the first synthetic inhibitors of aspartate semialdehyde dehydrogenase [136] as well as lysophosphatidic acid analogues, which increased the half-lives of analogues in cell culture [137],... 

All three must be inhibited before production of the intermediate ceases completely. In addition, each of the amino acids inhibits the first enzyme on its branch line away from aspartate-semialdehyde, so ensuring that the decrease in concentration of the metabolite affects only the production of the inhibiting amino acid. This is an example of control by enzyme multiplicity, although the individual inhibitions are brought about by the type of allosteric processes that have already been described. 

Aspartic Semialdehyde + NADPH + H+ <=> Homoserine + NADP+ (catalyzed by homoserine dehydrogenase). 

Aspartic semialdehyde (aspartate / -semialdehyde) is an intermediate in aspartate metabolism (see here). 

Aspartyl Phosphate + NADPH + H+ <=> Aspartic Semialdehyde + NADP+ + Pi (catalyzed by Aspartate Semialdehyde Dehydrogenase)... 

Aspartic / -Semialdehyde also participates in the reaction below that leads ultimately to lysine or to homoserine and methionine ... 

Aspartate has many fates, too. For example, its nitrogen is used in the biosynthesis of arginine and urea. Similar reactions are involved in purine nucleotide synthesis. The entire aspartate molecule is used in pyrimidine nucleotide biosynthesis. In plants and bacteria, aspartate is a precursor to three other amino acids (i.e., methionine,threonine, and isoleucine) via its conversion to homoserine (see here). Homoserine then leads in separate pathways to methionine and threonine. Threonine, in turn, can be converted to isoleucine. In bacteria, aspartic / -semialdehyde is a precursor to lysine. 

Figure 21.2 shows the sequence of reactions that converts glutamate to ornithine (a urea cycle intermediate). In this pathway, the energy-requiring reduction of glutamate to glutamicy-semialdehyde (see here) is comparable to the reduction of aspartate to aspartic semialdehyde (see here) and also leads to synthesis of proline (see here). In the synthesis of proline, however, cyclization is desirable because the cyclized product can be reduced with NADPH to proline. 

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. 

In Ramalingam and Woodard s synthesis (117) the protected aspartate semialdehyde 113 was synthesized from (2S)-aspartic acid and then converted to the labeled alcohols 115 using (R)- and (S)-alpine boranes (Scheme 33). Hydrolysis then led directly to (2S,4R)- and (2S,4S)-[4- H,]homoserine lactones 112. Since the enzyme aspartase may be used to prepare samples or (2S, 3R)-[3- H J- and (2S, 3S)-[2,3- H2]aspartate (see Section IX), the synthesis, or a modification using more direct reduction methods, could be... 

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