Glutamate biosynthesis

Figure Pathways for glutamate biosynthesis from 3- C alanine.

Ward H W, Thanki C. M., Peterson D. W., and Bradford H F (1982) Brain glutaminase activity in relation to transmitter glutamate biosynthesis. Biochem. Soc Trans 10, 369-370. 

Greenfield, S. and G.W. Claus. 1972. Nonfunctional tricarboxcylic acid cycle and the mechanism of glutamate biosynthesis in Acetobacter suboxydans. f. Bacteriol 112 1295-1301. 

Glutamate is synthesized from 2-oxoglutarate in the tricarboxylic acid (TCA) cycle by glutamate dehydrogenase (GDH) reaction, which is the main pathway for glutamate biosynthesis when nitrogen supply is sufficient. 

For glutamate production, a balanced supply of acetyl-CoA and oxaloacetate is important to proceed TCA cycle reactions toward 2-oxoglutarate, because it is a substrate for glutamate biosynthesis catalyzed by GDH. In particular, anaplerotic reactions, which supply oxaloacetate from the glycolytic intermediates, are caudal. C. glutamicum possesses two enzymes for anaplerotic reactions phosphoenolpyru-vate carboxylase (PEPC) encoded by ppc and pyruvate carboxylase (PC) encoded by pyc (Bormann et al. 1992 Eikmanns et al. 1995 O Regan et al. 1989 Peters-Wendisch et al. 1998). PC requires biotin as a cofactor for its activity. MFA was conducted to understand the role of these anaplerotic reactions in glutamate production. 

The 20 ammo acids listed m Table 27 1 are biosynthesized by a number of different path ways and we will touch on only a few of them m an introductory way We will exam me the biosynthesis of glutamic acid first because it illustrates a biochemical process analogous to a reaction we discussed earlier m the context of amine synthesis reductive ammatwn (Section 22 10)... 

L Glutamic acid is not an essential ammo acid It need not be present m the diet because animals can biosynthesize it from sources of a ketoglutaric acid It is however a key intermediate m the biosynthesis of other ammo acids by a process known as transamination L Alanine for example is formed from pyruvic acid by transamination from L glutamic acid... 

Nevertheless the biosynthesis of glutamine proceeds from glutamic acid The dif ference is that the endergonic process m Equation 1 is coupled with the strongly exer gome hydrolysis of ATP... 

Microorganisms requite several minerals such as ferrous and potassium ions which play important roles in glutamic acid fermentation. Other important culture conditions include regulating aeration stirring. The biosynthesis of L-glutamic acid is performed under regulated aerobic conditions. 

Reductive animations also occur in various biological pathways, fn the biosynthesis of the amino acid proline, for instance, glutamate 5-semjaldehyde undergoes internal imine formation to give 1-pyrrolinium 5-carboxylate, which is then reduced by nucleophilic addition of hydride ion to the C=N bond. 

Pyridoxamine phosphate serves as a coenzyme of transaminases, e.g., lysyl oxidase (collagen biosynthesis), serine hydroxymethyl transferase (Cl-metabolism), S-aminolevulinate synthase (porphyrin biosynthesis), glycogen phosphoiylase (mobilization of glycogen), aspartate aminotransferase (transamination), alanine aminotransferase (transamination), kynureninase (biosynthesis of niacin), glutamate decarboxylase (biosynthesis of GABA), tyrosine decarboxylase (biosynthesis of tyramine), serine dehydratase ((3-elimination), cystathionine 3-synthase (metabolism of methionine), and cystathionine y-lyase (y-elimination). 

The enzymes glutamate dehydrogenase, glutamine synthetase, and aminotransferases occupy central positions in amino acid biosynthesis. The combined effect of... 

Figure 28-8. Biosynthesis of proline from glutamate by reversal of reactions of proline catabolism.

Urea biosynthesis occurs in four stages (1) transamination, (2) oxidative deamination of glutamate, (3) ammonia transport, and (4) reactions of the urea cycle (Figure 29-2). 

Fig. 8.1 Biosynthesis of peptidoglycan. The large circles represent A -acetylglucosamine orN-acetylmuramic acid to the latter is linked initially a pentapeptide chain comprising L-alanine, D-glutamic acid and meso-diaminopiraelic acid (small circles) terminating in two D-alanine residues (small, darker circles). The lipid molecule is undecaprenyl phosphate. In the initial (cytoplasm) stage where inhibition by the antibiotic D-cycloserine is shown, two molecules of Dalanine (small circles) are converted by an isomerase to the D-forms (small, darker circles), alter which a ligase joins the two D-alanines together to produce a D-alanyl-D-alanine dipeptide.

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