Arginine urea cycle

One step in the urea cycle for ridding the body of ammonia is the conversion of argininosuccinate to the amino acid arginine plus fumarate. Propose a mechanism for the reaction, and show the structure of arginine. 

Urea cycle defects Failure to convert ammonia to urea via urea cycle (Fig. 40-5). Coma, convulsions, vomiting, respiratoryfailure in neonate. Often mistaken for sepsis of the newborn. Mental retardation, failure to thrive, lethargy, ataxia and coma in the older child. Associated with hyperammonemia and abnormalities of blood aminogram Low protein diet Acylation therapy (sodium benzoate, sodium phenylacetate) Arginine therapy in selected syndromes Hepatic transplantation... 

Valine, leucine, and isoleucine biosynthesis Lysine biosynthesis Lysine degradation Arginine and proline metabolism Histidine metabolism Tyrosine metabolism Phenylalanine metabolism Tryptophan metabolism Phenylalanine, tyrosine, and tryptophan biosynthesis Urea cycle and metabolism of amino groups... 

Arginine is converted to citrulline, which is released into the blood. This protects arginine from uptake and degradation in the urea cycle in the liver. Citrulline is released into the blood and transported to the kidney, where it is converted back to arginine (Chapter 8). 

Ornithine is a metabolically quite active amino acid, and the important precursor of pyrrolidine nucleus, which is found in pyrrolizidine alkaloids. Ornithine itself is a non-protein amino acid formed mainly from L-glumate in plants, and synthesized from the urea cycle in animals as a result of the reaction catalyzed by enzymes in arginine. 

Fig. 6.14. Biosynthesis of NO. The starting point of NO synthesis is arginine. Arginine is converted by NO synthase, together with O, and NAD PH, to NO and citruUine. Arginine can be regenerated from citrulline via reactions of the urea cycle.

Arginine Hyperargininemia LPI Urea cycle defects, HHH syndrome Hemolytic plasma ... 

FIGURE 3-8 Uncommon amino acids, (a) Some uncommon amino acids found in proteins. All are derived from common amino acids. Extra functional groups added by modification reactions are shown in red. Desmosine is formed from four Lys residues (the four carbon backbones are shaded in yellow). Note the use of either numbers or Creek letters to identify the carbon atoms in these structures, (b) Ornithine and citrulline, which are not found in proteins, are intermediates in the biosynthesis of arginine and in the urea cycle. 

Fig. 3-8b) deserve special note because they are key intermediates (metabolites) in the biosynthesis of arginine (Chapter 22) and in the urea cycle (Chapter 18). 

As we noted in Chapter 16, the enzymes of many metabolic pathways are clustered (p. 605), with the product of one enzyme reaction being channeled directly to the next enzyme in the pathway. In the urea cycle, the mitochondrial and cytosolic enzymes appear to be clustered in this way. The citrulline transported out of the mitochondrion is not diluted into the general pool of metabolites in the cytosol but is passed directly to the active site of argininosuccinate synthetase. This channeling between enzymes continues for argininosuccinate, arginine, and ornithine. Only urea is released into the general cytosolic pool of metabolites. 

Ammonia is highly toxic to animal tissues. In the urea cycle, ornithine combines with ammonia, in the form of carbamoyl phosphate, to form citrulline. A second amino group is transferred to citrulline from aspartate to form arginine—the immediate precursor of urea. Arginase catalyzes hydrolysis of arginine to urea and ornithine thus ornithine is regenerated in each turn of the cycle. 

Morris, S.M. (2002) Regulation of enzymes of the urea cycle and arginine metabolism. Annu. Rev. Nutr. 22, 87-105. 

Cleavage of argininosuccinate Argininosuccinate is cleaved to yield arginine and fumarate. The arginine formed by this reaction serves as the immediate precursor of urea. Fumarate produced in the urea cycle is hydrated to malate, providing a link with sev eral metabolic pathways. For example, the malate can be trans ported into the mitochondria via the malate shuttle and reenter... 

Correct answer = D. The amino nitrogen of dietary protein is excreted as urea. The two nitrogens enter the urea cycle as ammonia and aspartate. Urea is produced by the hydrolysis of arginine. The cleavage of argininosucdnate does not require ATP. The urea cycle occurs partly in the mitochondria. 

Arginine is cleaved by arginase to produce ornithine. [Note This reaction occurs primarily in the liver as part of the urea cycle (9ee p. 253).] Ornithine is subsequently converted to a-ketoglutarate. 

The 5-carbon skeleton of glutamic acid gives rise directly to those of proline, ornithine, and arginine. The reactions are outlined in Fig. 24-9. Arginine, in turn, is involved in the urea cycle, which is shown in detail in Fig. 24-10. Arginine is also a biosynthetic precursor of the polyamines. Another important biosynthetic product of glutamate metabolism is 8-aminolevulinate, a precursor to porphyrins (Eq. 24-44) in some organisms.139... 

Synthesis of arginine by the salvage pathway found in vertebrates and by the de novo pathway found in plants and bacteria. The final steps from ornithine to arginine are also part of the urea cycle (see fig. 22.7). 

Arginine and the urea cycle Argininemia and hyperammonemia Mental retardation Arginase... 

Next, in steps 7 and 8, N-l of the purine ring is contributed by aspartate. Aspartate forms an amide with the 4-carboxyl group, and the succinocarboxamide so formed is then cleaved with release of fumarate. Energy for carboxamide formation is provided by ATP hydrolysis to ADP and phosphate. These reactions resemble the conversion of cit-rulline to arginine in the urea cycle (chapter 22) and the conversion of IMP to AMP (see fig. 23.11). 

Because of the importance of the urea cycle, the capacity to convert ornithine into arginine is obvious. Complete loss of the ability to produce ornithine (a catalyst or carrier in the urea cycle) would limit the organism s control over production of its nitrogen waste product. 

Carbamoyl phosphate synthase contributes to two processes (a) the initial enzyme in the biosynthesis of pyrimidines and (b) a component in the synthesis of arginine biosynthesis or the urea cycle. In bacteria both of these processes occur within the same compartment. In human beings the carbamoyl phosphate synthase involved in the urea cycle is contained in... 

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