Glutamate metabolic fate

McKenna, M. C., Sonnewald, U., Huang, X. etal. Exogenous glutamate concentration regulates the metabolic fate of glutamate in astrocytes. /. Neurochem. 66 386-393,1996. 

The histidine catabolic pathway is discussed under Folate in Chapter 9. The material reveals that histidine is catabolized to produce glutamate. Glutamate in turn, can be converted to a-ketoglutarate and completely oxidized to CO in the Krebs cycle. In the study depicted in Figure 8,26, the dietary histidine was spiked with I Cjhistidine, The term "spiked" means that only a very small proportion of the histidine contained carbon-14. The metabolic behavior of the radioactive histidine, which can be followed, mirrors the metabolic fate of nonradioactive histidine in the diet. All of the CQz exhaled by the rats can be easily collected, The " COj present in the rat s breath can be measured by use of a liquid scintillation counter. The amount of CO2 produced directly mirrors the proportion of histidine, absorbed from the diet that was degraded the rat s body. 

Figure 4. Schematic representation of the metabolic fate of alanine in hepatocytes. Note that striking differences may exist between mammalian cell types on the one hand and individual amino acids on the other (see text). Solid and broken arrow lines refer to metabolic conversions and transport routes, respectively, and circles in membranes refer to specific transporters. Numbers refer to enzymes involved in alanine metabolism 1, alanine transaminase 2, pyruvate carboxylase 3, malate dehydrogenase 4, glutamate dehydrogenase 5, glutamine synthetase.

After orally ingested, L-theanine is absorbed into the blood circulation through the small intestinal tract s brush-border membrane and then distributed to tissues." " It is easily transported into the brain through the blood-brain barrier s leucine-preferring amino acid transporter system L-Theanine does not appear to accumulate. The metabolic fate of theanine after its oral administration was verified to be enzymatically hydrolyzed to glutamic acid and ethylamine in the blood, kidney, liver, and brain then most of the ethylamine generated was immediately excreted into urine, with only a part circulated in plasma. It is completely absent 24 h after administration. 

Glutamate metabolism. The metabolism of glutamate, including fates and sources of glutamate,... 

Alanine is the simplest L-amino acid found in protein. It has a simple metabolism, but complex physiological roles and functions. Alanine can transaminate reversibly with a-ketoglutarate, forming pyruvate and glutamate. This transamination occurs in many tissues, including liver and muscle. This is the only metabolic fate of pyruvate, other than protein synthesis. Therefore, alanine is glucogenic and is not required in the diet. 

Figure 30-12. Intermediates in tyrosine catabolism. Carbons are numbered to emphasize their ultimate fate. (a-KG, a-ketoglutarate Glu, glutamate PLP, pyridoxal phosphate.) Circled numerals represent the probable sites of the metabolic defects in type II tyrosinemia neonatal tyrosinemia alkaptonuria and 0 type I tyrosinemia, or tyrosinosis.

Aspartame, N-a-L-aspartyl-L-phenylalanine methyl ester, trade names NutraSweet , and Aspartil , is a dipeptide derivative. Like dipeptides aspartame is metabolised into the constituents, i.e. amino acids and methanol. Therefore studies into the metabolic behaviour and the fate of metabolites were carried out. Levels of blood aspartate and glutamate were measured after intake of high aspartame doses. Changes were transient and allegations of influences of high aspartame levels on brain function could never be verified. 

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.

Figure 9-3. Fates of the carbon skeletons upon metabolism of the amino acids. Points of entry at various steps of the tricarboxylic acid (TCA) cycle, glycolysis and gluconeogenesis are shown for the carbons skeletons of the amino acids. Note the multiple fates of the glucogenic amino acids glycine (Gly), serine (Ser), and threonine (Thr) as well as the combined glucogenic and ketogenic amino acids phenylalanine (Phe), tryptophan (Trp), and tyrosine (Tyr). Ala, alanine Cys, cysteine lie, isoleucine Leu, leucine Lys, lysine Asn, asparagine Asp, aspartate Arg, arginine His, histidine Glu, glutamate Gin, glutamine Pro, proline Val, valine Met, methionine.

Apart from glutamate, asdocytes also uptake neurodans-mitters like gamma amino butyric acid (GABA), aspartate, taurine, [3-alanine, serotonin, and catecholamines. The fate of all these neurodansmitters is to be metabolized within asdocytes. 

Joy and his colleagues have also monitored the fate of the asparagine carbon skeleton. Almost 75% of the [ CJasparagine supplied was metabolized in 210 min in the light but only 45% in the dark. Over 50% of the metabolized asparagine accumulated in a novel compound 2-hydroxysuccinamate (see Section III,C,2). 2-Oxosuccinamic acid was shown to be a precursor of 2-hydroxysuccinamic acid. Other amino acids were also labeled particularly aspartate, with lesser amounts in glutamate, homoserine, and alanine. 2-Hydroxysuccinamate was only slowly metabolized (approximately 20% in 210 min) although there was evidence of more rapid breakdown in the dark (Lloyd and Joy, 1978). 

The ammonia enters the portal vein and mixes with the metabolic nitrogen pool of the body. The fixation of this ammonia nitrogen into arginine, glutamic acid and utamine and aspartic acid represents a net contribution to nitrogen balance. The alternative fate of this ammonia is its conversion to urea prior to renal excretion. Thus the use of N-labelled ammonium salts or [ N]urea forms the basis of several common lines of clinical investigation. 

In considering amino acid catabolism, one must distinguish the catabolism of the carbon chain from that of the nitrogen moiety. The breakdown of the carbon chain of the amino acids yields carbon units that can be used in carbohydrate metabolism, acetate metabolism, or the metabolism of single carbon units. The fate of the carbon units of the individual amino acids has been discussed in other sections of this book, and only a synopsis of the results will be presented here. The carbon skeletons of isoleucine, phenylalanine, threonine, tryptophan, valine, histidine, alanine, arginine, aspartic acid, glycine, proline, glutamic acid, and hydroxyproline are ultimately converted to pyruvic acid. 

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