Aspartate kinase methionine

Lugli, J. Gaziola, S.A. Azevedo, R.A. Effects of calcium, S-adenosylmethio-nine, S-(2-aminoethyl)-L-cysteine, methionine, valine and salt concentration on rice aspartate kinase isoenzymes. Plant Sci., 150, 51-58 (2000)... 

The L-threonine biosynthetic pathway consists of five enzymatic steps from L-aspartate. E. coli has three aspartate kinase isoenzymes, key enzymes which catalyze the first reaction of the L-threonine biosynthetic pathway. The aspartate kinase isoenzymes I, II, and III encoded by the thrA, metL, and lysC genes, respectively, are affected by feedback inhibition by L-threonine, L-methionine, and L-lysine, respectively. C. glutamicum has only one aspartate kinase encoded by the lysC gene, which is subjected to feedback inhibition by L-lysine and... 

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...

Biosynthesis metabolism Asp is formed from oxaloacetic acid by aspartate aminotransferase (EC 2.6.1.1) and serves as starting material in the biosyntheses of threonine, methionine, and lysine. The first step is catalysed by aspartate kinase (EC 2.7.24) which only occurs in plants and microorganisms. This enzyme exists as 3 isozymes in Escherichia coli and exhibits a typical example of feedback regulation. Asp plays a central role in the biosyntheses of pyrimidines and purines. In the urea cycle Asp condenses with " citrulline to aigininosuccinate, a stimulating neuro-transmitter. ... 

Several plant aspartate kinases are activated by other amino acids such as valine, alanine, and isoleucine (Table HI). Activation does not appear to be a general effect of hydrophobic amino acids, since neither methionine nor leucine influence the activity of the maize enzyme yet, leucine has been reported to activate the enzyme isolated from Sinapsis alba and inhibit the enzyme from Helianthus annus. Interaction of these secondary effectors with the various aspartate kinases has not been fully explored, but several observations suggest a considerable degree of complexity. Alanine partially relieves threonine inhibition of the enzyme isolated from pea seedlings (Aames and Rognes, 1974). Lysine inhibition of maize aspartokinase is diminished in the presence of isoleucine, alanine, or valine (Bryan e/ al., 1970) and threonine, even though it does not inhibit the maize enzyme, counteracts... 

Lysine plus threonine severely inhibits growth of maize in a synergistic manner. Growth inhibition could result from combined effects of lysine on aspartate kinase and threonine on homoserine dehydrogenase, resulting in starvation for methionine. Growth inhibition by lysine -i- threonine can be overcome by supplying methionine. Bryan [1980) Miflin [1977). 

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). 

Fig. 5. Regulation of the enzymes of methionine biosynthesis and related pathways. Enzymes catalyzing the synthesis of methionine and 5 -adenosylmethionine (SAM) from cysteine are (1) cystathionine y-synthase, (2) j9-cystathionase, (3) methionine synthase, and (4) SAM synthetase. Enzymes associated with the synthesis and metabolism of phospbohomoserine which are relevant to the regulation of methionine synthesis are (5) aspartate kinase, (6) homoserine kinase, and (7)...

Isoenzymes of enzymes involved in the first step of a branched biosynthetic pathway may differ in their sensitivity to inhibitors. Thus the enzyme aspartate kinase catalyses in Escherichia coli the first step in the synthesis of lysine, methionine and threonine. Three isoenzymes occur, the synthesis and activity of one is suppressed by L-lysine, the activity of the second is depressed by L-threonine and the activity of the third by homoserine (an intermediate in methionine biosynthesis). Thus accumulation of L-lysine or L-threonine suppresses their own further S3mthesis but does not prevent the activity of the aspartokinase isoenzyme involved in methionine synthesis. Again peroxidase isoenzymes differ in their activity in destroying indol-3yl-acetic acid (lAA) and the pattern of peroxidase isoenzymes can be altered by feeding lAA or gibberellic acid (GA) to plant tissues. 

---