Ammonia urea synthesis

The two major chemicals based on synthesis gas are ammonia and methanol. Each compound is a precursor for many other chemicals. From ammonia, urea, nitric acid, hydrazine, acrylonitrile, methylamines and many other minor chemicals are produced (see Figure 5-1). Each of these chemicals is also a precursor of more chemicals. 

All defects in urea synthesis result in ammonia intoxication. Intoxication is more severe when the metabolic block occurs at reactions 1 or 2 since some covalent linking of ammonia to carbon has already occurred if citrulline can be synthesized. Clinical symptoms common to all urea cycle disorders include vomiting, avoidance of high-protein foods, intermittent ataxia, irritability, lethargy, and mental retardation. The clinical features and treatment of all five disorders discussed below are similar. Significant improvement and minimization of brain damage accompany a low-protein diet ingested as frequent small meals to avoid sudden increases in blood ammonia levels. 

Mak, J.Y., D. Heaven, D. Kubek, C. Sharp, and M. Clark, Synthesis Gas Purification in Gasification to Ammonia/Urea Complex, Gasification Technology Conference, October 2004. 

Heaven, D. et al., Synthesis gas purification in gasification to Ammonia/Urea plants, Gasification Technologies Conference, Washington, 2004. 

The formation and excretion of urea is the primary mechanism by which excess nitrogen, in the form of ammonia, is removed from the body. Surprisingly, it was found that the actual rate of urea synthesis exceeded considerably the rate of excretion of the urea. The interesting question, therefore, is what is the fate of this lost urea The answer is that urea enters the large intestine, where it is degraded by microorganisms that possess the enzyme urease, which catalyses the reaction ... 

In comparison, the vampire bat has a capacity for urea synthesis approximately 1000-fold greater than that of a human. A bat consumes one half of its weight in blood in 10-15 minutes so that the massive amount of protein that is metabolised produces a massive amount of ammonia which must be removed as quickly as possible. Indeed, it also ingests sufficient fluid so that it is too heavy to fly. Hence, it urinates very quickly. 

One of the nitrogen atoms for urea synthesis comes from ammonia and the other is donated by aspartate. 

In contrast to transamination reactions that transfer amino groups, oxidative deamination by gutamate dehydrogenase results in the lib eration of the amino group as free ammonia (Figure 19.11). These reactions occur primarily in the liver and kidney. They provide a-ketoacids that can enter the central pathway of energy metabolism, and ammonia, which is a source of nitrogen in urea synthesis. 

Flow of nitrogen from amino acids to urea. Amino groups for urea synthesis are collected in the form of ammonia and aspartate. 

Shown in Figure 10, this ammonia plant is a major part of the overall fertilizer site complex. Other major facilities include urea plant, steam system, and cooling water system. Most of the ammonia is used to make granulated urea product. The other raw material for urea synthesis is C02 from the C02 capture system in the ammonia plant, supplemented with a small stream from an adjacent business. The ammonia production and the C02 available from the ammonia plant are never precisely in balance, in part because of the overall stoichiometric yields of ammonia and C02 from the natural gas feedstock. C02 is the limiting feedstock for the urea plant and its production rate in the ammonia plant sets the urea plant production rate since there is no intermediate C02 storage to buffer the urea production from the C02 production rate. Ammonia that is produced in excess of that which is used to make urea... 

Dog No. 3 was omitted because of insufficient data. It is apparent that a marked uptake of ammonia occurs in tissues in metabolic acidosis. In alkalosis the uptake by tissues is only slightly greater than normal, and the arterial levels of ammonia are comparable with normal values. The elevation of blood ammonia which occurs on vigorous acidification of the animal might not be due to a drop in permeability with pH, but might be due to a phenomenon reported by Krebs and Henseleit (K4). Urea synthesis by liver slices is directly proportional to the pH and C02 content of the medium. Table 2, constructed from data reported in this paper, shows this dependence. 

Thus the drop in ammonia content of plasma in alkalosis may be related to the pH effect on urea synthesis rather than to the alterations in permeability caused by changes in pNHs. The treatment of hepatic coma by acidification with C02 would lower pH, inhibiting synthesis of urea. This would cause a rise in blood ammonia. The same type of change could be brought about by infusion of HC1, which would have a double effect on urea synthesis by lowering both pH and bicarbonate. It does not appear necessary to invoke a penetration hypothesis to explain the... 

In summary, then, the above short overview indicates that organisms from very early on probably minimized the threat of ammonia intoxication by metabolic mechanisms which serve to limit the amount of free ammonia in cell/body fluids formed in the first place. However, some formation and accumulation are inevitable. In mammals, and other animals that depend upon the urea cycle, this excess NH4+/NH3 together forms the precursor pool for urea synthesis. 

In starvation, the kidney uses glutamine, and glutamate derived from it, as a source of ammonia to buffer ketone bodies that are excreted. Some ammonia. goes to the liver for urea synthesis. The... 

In some mammalian cells, enzymes comprising partial spans of biosynthetic pathways are inside and some outside the mitochondrial matrix space. Therefore, in the liver, six mitochondrial membrane transport proteins are required for urea synthesis, three for gluconeogenesis [7,8], and three others participate in ammonia-genesis [9] in the kidney. The synthesis of neurotransmitter substances such as acetylcholine, glutamate and y-amino butyric acid requires the participation of metabolite transporters in mitochondrial membranes of nervous tissue [9,10]. 

As a rule, 2 mol bicarbonate are required for the synthesis of 1 mol urea. The amount of urea eliminated in the urine is approximately 500 mmol/day (ca. 30 g). Normally, only about 25% of the capacity of the urea cycle are used. It is therefore virtually impossible for hyperammonaemia to be a sequela to isolated NH4+ hyperproduction alone. In patients with liver cirrhosis, the capacity for urea synthesis is reduced by approximately 80%, i. e. there is a considerable decrease in ammonia detoxification in the periportal field, predominantly due to a function loss on the part of the perivenous scavenger cells. 

Gebhardt, R., Beckers, G., Gaunitz, F., Haupt, W., Jonitza, D., Klein, S., Scheja, L. Treatment of cirrhotic rats with L-ornithine-L-aspartate enhances urea synthesis and lowers serum ammonia levels. X. Pharmacol Exper. Ther. 1997 283 1-6... 

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)... 

Inhibition of ornithine breakdown in the liver with a favourable effect on urea synthesis (= definitive ammonia detoxication)... 

As early as 1932, H.A. Krebs and K. Henseleit discovered in their investigation of the amino acids that ornithine, even in small amounts, was capable of increasing urea synthesis from (toxic) ammonia. Otherwise, only arginine had a slight effect in this respect. (138) The following table shows which of the amino adds involved in the urea cycle are available for therapeutic purposes ... 

The biomolecular modes of action of ornithine have been the subject of several experimental investigations. Ornithine activates the enzymes carbamylphosphate synthetase and ornithine carbamyl transferase, which are necessary for the liver-specific process of urea synthesis (133,139) this occurs mainly in the periportal hepa-tocytes (= definitive ammonia detoxification). Glutamine synthesis (binding of ammonia to glutamate) takes place predominantly in the perivenous hepatocytes (= transitory ammonia detoxification). Large amounts of glutamate are necessary for this. Aspartate, ornithine... 

Fig. 3. Uptake of ammonia in pyrimidine synthesis and breakdown. Compounds found in excess in inherited disorders of urea synthesis are enclosed in rectangles. ASA, argininosuccinate.

The rise in glutamine level in hyperammonemia is highly significant. The formation of glutamic acid from a-ketoglutarate, and ammonia and its further conversion to glutamine by its reaction with ammonia, serves to regulate the level of ammonia in the blood, albeit to only a limited extent. Thus the initial effect of a defect of urea synthesis in the body... 

Cedrangolo et al (C5) and De Lorenzo (Dl) also postulated an alternative pathway on the basis of their experimental results on rats. The animals were injected with a-methyl aspartate, a specific inhibitor for argininosuccinate synthetase. No effect on urea excretion was observed, but there was complete inhibition of urea synthesis from citrulline in liver homogenates prepared from injected animals, as well as increased susceptibility to ammonia intoxication. However, this inhibition was not confirmed by Crokaert and Baroen (C15, C16, C17), although they did confirm the lack of any effect on urea excretion. The experimental basis for this suggestion is therefore in doubt. 

Within the liver, elimination of ammonia occurs via urea synthesis (Chapter 17). Since urea is uncharged, it does not disturb the acid-base balance. Many interorgan relationships in protein and nitrogen homeostasis arose because of the role that the liver plays in excess nitrogen excretion. 

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