Aspartate metabolic fate

Figure 7. Metabolic fate of oxaloacetate in mammalian tissues. 1, Aspartate aminotransferase 2, citrate synthetase 3, malate dehydrogenase 4, P-enolpy-ruvate carboxykinase.

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 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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