Glutamate/glutamic acid synthesis

This method is particularly interesting because it is a close laboratoiy analogy of a pathway by which some amino acids are bio.synthesized in nature. For example, the major route for glutamic acid synthesis in most organisms is by reductive amination of or-ketoglutaric acid. The biological... 

M.H. Sung, C. Park, C.J. Kim, H. Poo, K. Soda, M. Ashiuchi, Natural and edible biopolymer poly-gamma-glutamic acid synthesis, production, and applications, Chem. Rec. 5 (2005) 352-366. 

Kino K, Arai T, Arimura Y (2011) Poly-Alpha-Glutamic Acid Synthesis Using a Novel Catalytic Activity of RimK from Escherichia coli K-12. Appl. environ, microbiol. 77 p. 2019-25. 

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)... 

Chemical Production. Glyciae, DL-methionine, and dl-alanine ate produced by chemical synthesis. From 1964 to 1974, some glutamic acid was produced chemically (48). The synthetic amino acid with the largest production is DL-methionine from actoleia (see Acrolein and derivatives). The iadustrial production method is shown ia the foUowiag (210). 

An estimation of the amount of amino acid production and the production methods are shown ia Table 11. About 340,000 t/yr of L-glutamic acid, principally as its monosodium salt, are manufactured ia the world, about 85% ia the Asian area. The demand for DL-methionine and L-lysiae as feed supplements varies considerably depending on such factors as the soybean harvest ia the United States and the anchovy catch ia Pern. Because of the actions of D-amiao acid oxidase and i.-amino acid transamiaase ia the animal body (156), the D-form of methionine is as equally nutritive as the L-form, so that DL-methionine which is iaexpensively produced by chemical synthesis is primarily used as a feed supplement. In the United States the methionine hydroxy analogue is partially used ia place of methionine. The consumption of L-lysiae has iacreased ia recent years. The world consumption tripled from 35,000 t ia 1982 to 100,000 t ia 1987 (214). Current world consumption of L-tryptophan and i.-threonine are several tens to hundreds of tons. The demand for L-phenylalanine as the raw material for the synthesis of aspartame has been increasing markedly. 

Glutamic acid dehydrogenase is widely distributed in microorganisms and higher plants as a catalyst in the synthesis of L-glutamic acid from a-ketoglutaric acid and free ammonia. Transaminase is contained in a wide variety of microorganisms. 

The first L-folic acid synthesis was based on the concept of a thiee-component, one-pot reaction (7,22). Ttiainino-4(3JT)-pyrirnidinone [1004-45-7] (10) was reacted simultaneously with C -dibromo aldehyde [5221-17-0] (11) and j )-aminoben2oyl-L-glutamic acid [4271-30-1] (12) to yield fohc acid (1). 

Another viable method for the synthesis of L-foUc acid (1) starts from 6-formylpterin (23). The diester of L-glutamic acid (24) is condensed with 6-formylpterin (23). Reduction of the Schiff base with sodium borohydride is followed by hydrolysis to yield L-foUc acid (37). 

The first are competitors of PABA (p-aminobenzoic acid) and thus intermpt host de novo formation of the tetrahydrofoUc acid required for nucleic acid synthesis. Examples of dmgs that fall into this group are the sulfones and sulfonamides. The most weU-known of the sulfones is dapsone (70, 4,4 -diaminodiphenyl sulfone, DDS), whose toxicity has discouraged its use. Production of foHc acid, which consists of PABA, a pteridine unit, and glutamate, is disturbed by the substitution of a sulfonamide (stmcturally similar to PABA). The antimalarial sulfonamides include sulfadoxine (71, Fanasd [2447-57-6]) sulfadiazine (25), and sulfalene (72, sulfamethoxypyrazine [152-47-6] Kelfizina). Compounds of this group are rapidly absorbed but are cleared slowly. 

Both threo- (14) and eo f >"4-fluoro-DL-glutamic acid (/5) are noncompetitive inhibitors of glutamine synthase, an enzyme that catalyzes the synthesis of glutamine from L-glutamic acid and ammonia. This mhibibon may explain the... 

The Dmab group was developed for glutamic acid protection during Fmoc/r-Bu based peptide synthesis. The group shows excellent acid stability and stability toward 20% piperidine in DMF. It is formed from the alcohol using the DCC protocol for ester formation and is cleaved with 2% hydrazine in DMF at rt. ... 

A convenient method for the stereoselective synthesis of sv -3-substituled glutamic acids is based upon the Michael addition oflithium enolates of jV.A -dibenzylglycinates to a,/J-unsatu-... 

Ail extremely useful method for the asymmetric synthesis of substituted amino acids, in particular glutamic acids, is based on optically active bislactim ethers of cyclodipeptides. The lithium etiolates of bislactim ethers (which are prepared easily from amino acids) undergo 1,4-addition to various a,/ -unsaturated esters to give -substituted 2,5-dihydropyrazine-propanoates203-205 with high diastereofacial selectivity, ratio (R/S) > 140-200 1. 

Many microorganisms can synthesise amino acids from inorganic nitrogen compounds. The rate and amount of some amino acids may exceed the cells need for protein synthesis, where the excess amino acids are excreted into the media. Some microorganisms are capable of producing certain amino acids such as lysine, glutamic acid and tryptophan. 

There is another fundamental difference between folate utilization in microbial and mammalian cells. Bacteria and protozoa are unable to take up exogenous folate and must synthesize it themselves. This is carried out in a series of reactions involving first the synthesis of dihydropteroic acid from one molecule each of pteridine and p-aminobenzoic acid (PABA). Glutamic acid is then added to form DHF which is reduced by DHFR to THF. Mammalian cells do not make their own DHF, instead they take it up firm dietary nutrients and convert it to THF using DHFR. 

If a substance is to be a NT it should be possible to demonstrate appropriate enzymes for its synthesis from a precursor at its site of action, although peptides are transported to their sites of location and action after synthesis in the axon or distal neuronal cell body. The specificity of any enzyme system must also be established, especially if they are to be modified to manipulate the levels of a particular NT, or used as markers for it. Thus choline acetyltransferase (ChAT) may be taken as indicative of ACh and glutamic acid decarboxylase (GAD) of GABA but some of the synthesising enzymes for the monoamines lack such specificity. 

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