Glutamate biosynthesis, pathways

Figure Pathways for glutamate biosynthesis from 3- C alanine.

Although the GOGAT reaction consumes one NADPH it produces two molecules of glutamate that can yield, via GDH, two NADPH that can in turn serve as an electron source for the anti-oxidative enzymes glutathione reductase (GR) and thioredoxin reductase (TrxR see p. 264-266) glutamine could also be used in pyrimidine biosynthesis. (The glutamate metabolic pathway can be found online at http //sites.huji.ac. il/malaria/maps/glutamatemetpath.html last accessed 16 July 2008.)... 

Dihydrofolate is assembled by a convergent pathway from a pteridine precursor (6-hydroxymethyldihydrop-terin pyrophosphate), 4-aminobenzoate, and glutamate (Figure 2). The following paragraphs describe the biosynthesis pathways of 4-aminobenzoate and the pteridine precursor, 6-hydroxymethyl-dihydropterine... 

Enzymes catalyze almost every metabolic reaction in extant cells. A few tmusually facile reactions, such as cyclization of L-glutamate 7-semialdehyde to form pyrroline-5-carboxylate in the proline biosynthesis pathway and decarboxylation of 2-amino-3-oxo-4-phosphonooxybutyrate in the pyridoxal phosphate (PLP) synthesis pathway, do not require acceleration to satisfy the demands of the cell. For all other reactions, catalysis is required because the rates of nonenzymatic reactions are very slow. Modern enzymes are marvelous catalysts. They accelerate reactions by up to 20 orders of magnitude, prevent side reactions of reactive intermediates, and catalyze stereoselective and stereospecific reactions. Further, they are often exquisitely regulated by small molecule ligands. 

For large-scale recombinant production of bacterial polymers, non-polymer producing bacteria were exposed to biosynthesis pathways. Polymers such as PHA, CGP (cyanophycin granule peptide), HA (hyaluronic acid), and PGA [poly-y-glutamate] were produced by these methods [89, 85-96]. For example, recombinant E.coli [89] was fermented for the lai e-scale production of PHA [89]. In addition the PHB biosynthesis genes of Ralstonia eutropa were harbored in E.coli to produce poljmers such as PHA composed of (R)-S-hydroxybutyrate and (R)-3-hydroxyvalerate and/or (R)-3-hydroxyhexanoate which showed preferable properties for use in industrial applications [97-99, 85-96]. 

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. 

The 20 fflnino acids listed in Table 27.1 are biosynthesized by a number of different pathways, and we will touch on only a few of them in an introductory way. We will examine the biosynthesis of glutamic acid first because it illustrates a biochemical process analogous to a reaction we discussed earlier in the context of amine synthesis, reductive amination (Section 22.10). 

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. 

S ATP 4- L-glutamate <2, 4, 5> (<2> the enzyme catalyzes the first step in the pathway from glutamate to proline [2,3] <2> enzyme is involved in biosynthesis of proline [4] <4> enzyme form GKl is involved in biosynthesis of L-Pro, enzyme form GK 2 is involved in biosynthesis of glutamine and the function of enzyme form GK 3 has not been found [6] <4> enzyme GK 1 is the first enzyme of the proline biosynthetic pathway... 

FIGURE 22-15 Biosynthesis of six essential amino acids from oxalo-acetate and pyruvate in bacteria methionine, threonine, lysine, isoleucine, valine, and leucine. Here, and in other multistep pathways, the enzymes are listed in the key. Note that L,L-a,e-diaminopimelate, the product of step (HI), is symmetric. The carbons derived from pyruvate (and the amino group derived from glutamate) are not traced beyond this point, because subsequent reactions may place them at either end of the lysine molecule. 

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