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Urea Cycle Nitrogen containing compounds cannot be stored in the body and therefore any excess of these

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Introduction

Urea Cycle Nitrogen containing compounds cannot be stored in the body and therefore any excess of these must be excreted to prevent poisoning. Most aquatic species, such as bony fishes, excrete amino nitrogen as ammonia and are thus called amonotelic animals; most terrestrials animals excrete amino nitrogen in the form of urea and are thus ureotelic; and birds and reptiles excrete amino nitrogen as uric acid and are called uricotelic. Plants recycle virtually all amino groups, and nitrogen excretion occurs only under very unusual circumstances hence there is no general pathway for nitrogen excretion. In ureotelic organisms, the ammonia in the mitochondria of hepatocytes is converted to urea via the urea cycle. The urea cycle was discovered by Hans Krebs and Kurt Henseleit who found it almost exclusively occurs in the liver. In their experiments they revealed that urea formation from ammonia was greatly accelerated by adding any one of three amino acids: ornithine, citrulline, or arginine. ...read more.

Middle

This reaction forms the second non standard amino acid - citrulline, this then has to be transported to the cytosol where the remaining three reactions take place. Third reaction involves citrulline being condensed with aspartate, the source of the second nitrogen atom in urea, by the enzyme argininosuccinate synthetase to form argninosuccinate. This reaction is driven by the hydrolysis of ATP to AMP and PPi, with subsequent hydrolysis of the pyrophosphate. Thus both of the high energy bonds in ATP are ultimately cleaved. Fourthly argninosuccinase then removes the carbon skeleton of aspartate from argninosuccinate in the form of fumarate, leaving the nitrogen atom on the other product arginine. As the urea cycle also produces arginine, this amino acid is classified as non-essential in ureotolic organisms. Fifthly and finally urea is formed from arginine by the action of arginase with the regeneration of ornithine. The orninthine is then transported back into the mitochondrion ready to be combined with another molecule of carbamoyl phosphate. ...read more.

Conclusion

All five enzymes are synthesised at higher rates during starvation or in animals on very high proteins diets than in well fed animals on diets containing primarily carbohydrates and fats. Animals on protein free diets produce even lower levels of urea cycle enzymes. On a shorter scale , allosteric regulation of at least one key enzyme is involved in adjusting flux through the cycle. The first enzyme in the pathway, carbamoyl phosphate synthetase I is allosterically activiated by N-acetylglutamate, which is synthesised from acetyl CoA and glutamate. N-acetylglutamate synthase is in turn activated by arginine, a urea cycle intermediate that accumulates when urea production is too slow to accommodate the ammonia produced by amino acid catabolism In conclusion ureotelic organisms need to convert ammonia to nitrogen, in order to reduce toxicity levels in the body. This is done by the urea cycle, using three non-standard amino acids ammonia is converted to urea via 5 enzymatic reactions, these reactions are closely intertwined with the citric acid cycle. ...read more.

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