Branched chain amino acid glutamate

Branched-chain amino acid glutamate transaminase... 

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). 

Transaminase enzymes (also called aminotransferases) specifically use 2-oxoglutarate as the amino group acceptor to generate glutamate but some have a wide specificity with respect to the amino donor. For example, the three branched-chain amino acids leucine, isoleucine and valine, all serve as substrates for the same enzyme, branched-chain amino acid transaminase, BCAAT ... 

Amino acids and some small peptides are absorbed into the enterocytes in the jejnnnm. The transport of amino acids from the lumen into the ceU is an active process, coupled to the transport of Na ions down a concentration gradient. There are at least six carrier systems with different amino acid specificities neutral amino acids (i.e. those with no net charge, e.g. branched-chain amino acids) neutral plus basic amino acids imino acids (proline, hydroxyproline) and glycine basic amino acids (e.g. arginine and lysine) P-amino acids and taurine acidic amino acids (glutamic and aspartic acids). 

Figure 8.17 The metabolism of branched-chain amino acids in muscle and the fate of the nitrogen and oxoacids. The a-NH2 group is transferred to form glutamate which is then aminated to form glutamine. The ammonia required for aminab on arises from glutamate via glutamate dehydrogenase, but originally from the transamination of the branded chain amino acids. Hence, they provide both nitrogen atoms for glutamine formation.

The amino acids, aspartate and glutamate, are not taken up from the blood but are synthesised in the brain. This requires nitrogen (for the -NH2 groups) which is obtained from branched-chain amino acids via transamination, as in other tissues. 

Branched-chain amino acids that are metabolised in muscle transfer nitrogen to glutamate to form glutamine (See Figure 8.23). 

Free amino acids are further catabolized into several volatile flavor compounds. However, the pathways involved are not fully known. A detailed summary of the various studies on the role of the catabolism of amino acids in cheese flavor development was published by Curtin and McSweeney (2004). Two major pathways have been suggested (1) aminotransferase or lyase activity and (2) deamination or decarboxylation. Aminotransferase activity results in the formation of a-ketoacids and glutamic acid. The a-ketoacids are further degraded to flavor compounds such as hydroxy acids, aldehydes, and carboxylic acids. a-Ketoacids from methionine, branched-chain amino acids (leucine, isoleucine, and valine), or aromatic amino acids (phenylalanine, tyrosine, and tryptophan) serve as the precursors to volatile flavor compounds (Yvon and Rijnen, 2001). Volatile sulfur compounds are primarily formed from methionine. Methanethiol, which at low concentrations, contributes to the characteristic flavor of Cheddar cheese, is formed from the catabolism of methionine (Curtin and McSweeney, 2004 Weimer et al., 1999). Furthermore, bacterial lyases also metabolize methionine to a-ketobutyrate, methanethiol, and ammonia (Tanaka et al., 1985). On catabolism by aminotransferase, aromatic amino acids yield volatile flavor compounds such as benzalde-hyde, phenylacetate, phenylethanol, phenyllactate, etc. Deamination reactions also result in a-ketoacids and ammonia, which add to the flavor of... 

Ryberg H, Askmai k H, Persson L (2003) A double blind randomized clinical dial in amyod ophic lateral sclerosis using lamod igine Effects on CSF glutamate, aspai tate, branched chain amino acid levels and clinical pai ameters. Acta Neurol Scand 108 1-8. 

Fig. 15.1 Branched-chain amino acid cycle and glutamate cycle in the brain (A = astrozyte, N = neuron, BBB = blood-brain barrier, GNT = glutamate neurotransmitter, BCAA = branched-chain amino acids, BCKA = branched-chain keto acids) (150)...

Branched-chain amino acids apparently stimulate the urea cycle. Carbamoylphosphate synthetase, which channels ammonia into the urea cycle, is induced by ornithine and N-acetylglutamate as a cofactor of urea synthesis. Here, BCAA follow two modes of action (i.) they stimulate the synthesis of N-acetylglutamate via synthetase formed from glutamate and acetyl CoA, and (2.) they inhibit omithine-keto acid transferase, which is the enzyme responsible for ornithine degradation, leading to an increase in ornithine concentration. Ammonia detoxication is thus stimuiated by two regu-iatory mechanisms, (s. fig. 40.2)... 

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. 

In laboratory-scale experiments, solutions containing 200-600 mM keto acid were transaminated to the corresponding branched-chain L-amino acid, with a concentration of L-glutamate between 50 mM and 100 mM and a 1.1 molar excess of l-aspartate. Yields obtained for the branched-chain amino acids have typically been in the range of 80-90 % based on starting with a 2-keto acid [10l... 

Tyrosine can arise from two major sourcesone is dietary tyrosine and the other is from phenylalanine that is converted to tyrosine. Tyrosine is further metabolized via a number of different pathways the major quantitative pathway of metabolism occurs in the liver. Almost all essential amino-acid metabolism, with the exception of the branched-chain amino acids, occurs primarily in the liver. Tyrosine is transaminated, with a-ketoglutarate being the acceptor, to form / -hydroxyphenyl pyruvate and glutamate (Fig. 19.2). This reaction is freely reversible. 

Synthesis of glutamate removes a-ketoglutarate from the TCA cycle, thereby decreasing the regeneration of oxaloacetate in the TCA cycle. Because oxaloacetate is necessary for the oxidation of acetyl CoA, oxaloacetate must be replaced by anapierotic reactions. There are two major types of anapierotic reactions (1) pyruvate carboxylase and (2) the degradative pathway of the branched-chain amino acids, valine and isoleucine, which contribute succinyl CoA to the TCA cycle. This pathway uses B12 (but not folate) in the reaction catalyzed by methylmalonyl CoA mutase. 

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