3-Aspartate semialdehyde lysine synthesis

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. 

Fig. 10. Schematic representation of the split biosynthetic pathway of L-lysine in wildtype Corynebacterium glutamicum including the branch point of aspartate semialdehyde distribution. The metabolites derived from the aldehyde via the synthase activity are D,L-di-aminopimelate and L-lysine, whereas that resulting from dehydrogenase activity are L-threo-nine, L-methionine, and L-isoleucine. The activity of the dehydrogenase is inhibited at elevated L-threonine concentrations and its synthesis is repressed by L-methionine. Accumulating intracellular lysine causes feedback inhibition of aspartate kinase and activates lysE transcription...

A further flux control step within L-lysine synthesis is the aspartate semialdehyde branch point. The aldehyde is either used as a substrate for the homoserine dehydrogenase, or together with pyruvate as a substrate for the dihydrodipicolinate synthase (Fig. 10). Whereas the homoserine dehydrogenase is allosterically controlled in its catalytic activity by the L-threonine concentration... 

Seven enzyme catalyzed reactions are required for the synthesis of lysine from pyruvate and aspartate semialdehyde as illustrated in Fig. 3. However, enzymes catalyzing only the first and last of these reactions have been isolated from plants. Dihydropicolinate synthase facilitates the condensation of the precursors during a reaction which presumably proceeds in two steps. A double bond between the C-4 of the semialdehyde and the methyl carbon of pyruvate would be formed, with the loss of water, followed by spontaneous ring closure and the loss of a second molecule of water. Catalysis of this reaction in plant extracts was first demonstrated by Cheshire and Miflin (1975) using maize seedlings as the source of the enzyme. Mazelis et al. (1977) detected the enzyme in extracts obtained from six different taxonomic families of plants and partially purified the enzyme from wheat germ. Only the L isomer of aspartate semialdehyde was active as a substrate of this enzyme and strong cooperativity was noted when the concentration of pyruvate was varied. A dihydropicolinate synthase has also been isolated from carrot cells (Matthews and Widholm, 1978). 

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... 

L-Threonine is synthesized from L-aspartic acid via L-aspartic acid-4-phosphate and L-aspartic-jS-semialdehyde (Fig. 203). The latter is a precursor of L-lysine (D 18) as well as of L-homoserine (D 12). L-Threonine is formed from L-homoserine by synthesis of the 4-phosphate and shift to the hydroxyl group by a pyridoxal-phosphate-dependent enzyme. 

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