Urea from ammonia a) Outline the biosynthesis of urea from ammonia in the mammalian liver.

The build up of nitrogen in the blood in the form of ammonia can prove to be very detrimental to the health of many organisms. Hence the body must have systems in place that would prevent such occurrences or control them. Urea is the main end product of nitrogen metabolism in mammals. It is synthesized in the liver of these organisms (mammals) via the urea cycle. The urea cycle basically entails the conversion of ammonia into the less toxic nitrogenous compound urea. This cycle occurs in the mitochondria and cytosol of the liver cells. It (the cycle that is) goes as follows: A) Initially carbamoyl phosphate is produced by the condensation and activation of ammonia (from the oxidative deamination of glutamate by glutamate dehydrogenase) and carbon dioxide. This reaction is catalyzed by the enzyme carbamoyl phosphate synthetase and requires the hydrolysis of two ATP molecules. The process (hydrolysis) makes the reaction between ammonia and carbon dioxide irreversible. This takes place in the mitochondrion of the liver cell. Here the first nitrogen need for the production of urea is provided. B) Still in the mitochondrion, a transfer of the carbamoyl group from carbamoyl phosphate to ornithine is carried out by the transferase enzyme transcarbamoylase resulting in the formation of an amino acid called citrulline. This product is then transported out of the cell energy house, the mitochondrion, and into the cytosol. C) A condensation reaction between citrulline and aspartate facilitated by the enzyme argininosuccinate synthetase provides the next substrate in the cycle, argininosuccinate. This reaction which is driven by the hydrolysis of ATP to AMP and PPi, with the subsequent hydrolysis of the pyrophosphate provides the second nitrogen molecule needed in the formation of urea. D) This is followed by the argininosuccinases removal of the carbon skeleton of aspartate from argininosuccinate giving rise to fumerate as well as the immediate precursor of urea, arginine. E) Urea is finally formed by the action of arginase that is the cleaving or hydrolysis of the arginines carbon backbone. Ornithine which is regenerated is transported back

to the mitochondrion where it would combine with another carbamoyl phosphate molecule. Urea is then secreted into the blood and taken up by urine for excretion. b) Differentiate between transamination and oxidative deamination. Transamination is a reaction resulting in the exchange or as the name suggests transfer of an amine group of one acid with that of a ketone group of another amino acid; that is a double replacement reaction. This occurs primarily in the liver and is catalyzed by enzymes called transminases. Oxidative deamination occurs in all living tissue under aerobic conditions. This process involves a transamination step -the transfer of the amine group of an acid with a ketone group of another amino acid. However differences exist between these two processes in the fact that transamination simply involves the transfer of amino groups from a large variety of amino acid in to two or three amino acids. It does not yield nitrogen from the amino acids. While oxidative deamination would release nitrogen from their reactions as ammonia. References Berg M. Jeremy, e tal; 2005; Biochemistry 5th Edition; WH Freeman and Company; United Kingdom Hames David, e tal; 2005; Biochemistry 3rd Edition; Hoopers, Taylor and Frances group; United Kingdom King W. Michael; 9/03/2012; Urea cycle; http://themedicalbiochemistrypage.org/nitrogenmetabolism.php;5/03/2012