Glutamate amino acid synthesis

The first example of a dynamic flux analysis was a study performed in the 1960s [269]. In the yeast Candida utilis, the authors determined metabolic fluxes via the amino acid synthesis network by applying a pulse with 15N-labeled ammonia and chasing the label with unlabeled ammonia. Differential equations were then used to calculate the isotope abundance of intermediates in these pathways, with unknown rate values fitted to experimental data. In this way, the authors could show that only glutamic acid and glutamine-amide receive their nitrogen atoms directly from ammonia, to then pass it on to the other amino acids. 

J Kovacs, R Gianotti, A Kapoor. Polypeptides with known repeating sequence of amino acids. Synthesis of poly-L-glutamyl-L-alanyl-L-glutamic acid and polyglycyl-L-phenylalanine through pentachlorophenyl active ester. J Am Chem Soc 88, 2282, 1966. 

The ammonia can then be utilised for amino acid synthesis in some or all of the microorganisms in the intestine, a process requiring the enzyme glutamate dehydrogenase to incorporate the ammonia into glutamate... 

Your liver is also a site for amino acid synthesis such as Serine, Glycine, Glutamic acid and Glutamine. This means that the liver will hang on to some amino acids for bio-synthesis while passing others onto the general circulation for transportation to other organs and tissue. 

Finally, a pyridoxal transamination converts the two keto-acids stereospecifically to the corresponding amino acids, valine (R = Me) and isoleucine (R = Et). The donor amino acid is probably glutamate—-it usually is in amino acid synthesis. 

On the basis of the similarities in their synthetic pathways, the amino acids can be grouped into six families glutamate, serine, aspartate, pyruvate, the aromatics, and histidine. The amino acids in each family are ultimately derived from one precursor molecule. In the discussions of amino acid synthesis that follow, the intimate relationship between amino acid metabolism and several other metabolic pathways is apparent. Amino acid biosynthesis is outlined in Figure 14.4. 

Herbicides that inhibit enzymes important for amino acid synthesis account for 28% of the herbicide market. Just three enzymes are involved the enzyme that adds phosphoenolpyruvate to shikimate-3-phoshate in the pathway leading to aromatic compounds, the enzyme that makes glutamine from glutamate and ammonia, and the first common enzyme in the biosynthesis of the branched-chain amino acids. 

The glutamate family of transaminases is very important because the ketoacid corresponding to glutamate is a-ketoglutarate, one of the citric acid cycle intermediates. This provides a link between the citric acid cycle and amino acid metabolism. These transaminases provide amino groups for amino acid synthesis and collect amino groups during catabolism of amino acids. 

Fig. 20.17. Efflux of intermediates from the TCA cycle. In the liver, TCA cycle intermediates are continuously withdrawn into the pathways of fatty acid synthesis, amino acid synthesis, gluconeogenesis, and heme synthesis. In brain, a-ketoglutarate is converted to glutamate and GABA, both neurotransmitters.

Fig. 38.8. Role of glutamate in amino acid synthesis. Glutamate transfers nitrogen by means of transamination reactions to a-keto acids to form amino acids. This nitrogen is either obtained by glutamate from transamination of other amino acids or from NH4 by means of the glutamate dehydrogenase (GDH) reaction. PLP = pyridoxal phosphate.

One of the consequences of amino acid catabolism is the production of ammonia, which is highly toxic. Some of this may be used in amination during amino acid synthesis in the body. In this case, ammonia reacts with a-ketoglutarate to give glutamate. 

In the case of hyperphenylalaninaemia, which occurs ia phenylketonuria because of a congenital absence of phenylalanine hydroxylase, the observed phenylalanine inhibition of proteia synthesis may result from competition between T.-phenylalanine and L-methionine for methionyl-/RNA. Patients sufferiag from maple symp urine disease, an inborn lack of branched chain oxo acid decarboxylase, are mentally retarded unless the condition is treated early enough. It is possible that the high level of branched-chain amino acids inhibits uptake of L-tryptophan and L-tyrosiae iato the brain. Brain iajury of mice within ten days after thek bkth was reported as a result of hypodermic kijections of monosodium glutamate (MSG) (0.5—4 g/kg). However, the FDA concluded that MSG is a safe kigredient, because mice are bom with underdeveloped brains regardless of MSG kijections (106). 

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. 

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