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Nitrogenous Waste in Terrestrial Animals: the Urea Cycle

Nitrogenous Waste in Terrestrial Animals: The Urea Cycle

The urea cycle is the primary mechanism by which mammals convert ammonia to urea. Urea is made in the liver and excreted in urine. The overall chemical reaction by which ammonia is converted to urea is 2 NH3 (ammonia) + CO2 + 3 ATP + H2O → H2N-CO-NH2 (urea) + 2 ADP + 4 Pi + AMP.

The urea cycle utilizes five intermediate steps, catalyzed by five different enzymes, to convert ammonia to urea, as shown in the figure below. The amino acid L-ornithine gets converted into different intermediates before being regenerated at the end of the urea cycle. Hence, the urea cycle is also referred to as the ornithine cycle. The enzyme ornithine transcarbamylase catalyzes a key step in the urea cycle and its deficiency can lead to accumulation of toxic levels of ammonia in the body. The first two reactions occur in the mitochondria and the last three reactions occur in the cytosol. Urea concentration in the blood, called blood urea nitrogen or BUN, is used as an indicator of kidney function.

 The urea cycle begins in the mitochondrion, where bicarbonate (HCO3) is combined with ammonia (NH3) to make carbamoyl phosphate. Two ATP are used in the process. Ornithine transcarbamylase adds the carbamoyl phosphate to a five-carbon amino acid called ornithine to make L-citrulline. L-citrulline leaves the mitochondrion, and an enzyme called arginosuccinate synthetase adds a four-carbon amino acid called L-aspartate to it to make arginosuccinate. In the process, one ATP is converted to AMP and PPi. Arginosuccinate lyase removes a four-carbon fumarate molecule from the arginosuccinate, forming the six-carbon amino acid L-arginine. Arginase-1 removes a urea molecule from the L-arginine, forming ornithine in the process. Urea has a single carbon double-bonded to an oxygen and single-bonded to two ammonia groups. Ornithine enters the mitochondrion, completing the cycle.

The urea cycle converts ammonia to urea.

Evolution Connection: Excretion of Nitrogenous Waste

The theory of evolution proposes that life started in an aquatic environment. It is not surprising to see that biochemical pathways like the urea cycle evolved to adapt to a changing environment when terrestrial life forms evolved. Arid conditions probably led to the evolution of the uric acid pathway as a means of conserving water.

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