Urea Cycle Research Paper

The Urea Cycle

The ornithine cycle (also known as the 'urea cycle ') is a cycle of biochemical reactions occurring in many animals that produce urea ((NH2)2CO) from ammonia (NH3). This cycle was the first metabolic cycle discovered by Hans Krebs and Kurt Henseleit in 1932, five years before the discovery of the TCA cycle. In mammals, the urea cycle takes place primarily in the liver, and to a lesser extent in the kidney.

Ammonia Toxicity

Every amino acid contains at least one amino group. Therefore every amino acid degradation pathway has a key step where the amino group is removed. In short amino acid catabolism generates ammonia. Brain tissue is very sensitive to ammonia. Ammonia intoxication produces a comatose state. Cells get rid of

Ammonia is produced in the mitochondrial matrix by the enzymatic activities of glutaminase and glutamate dehydrogenase. Carbamoyl phosphate synthetase I is the enzyme that takes the ammonia, bicarbonate and 2 molecules of ATP to produce carbamoyl phosphate. This enzyme activates bicarbonate by the same method used by biotin containing enzymes. In fact carbamoyl phosphate synthetase is homologous to the biotin family of enzymes. Carbamoyl phosphate synthetase I activates bicarbonate by phosphorylation with ATP to form carboxyphosphate. Ammonia then reacts with carboxyphosphate to from a carbamate intermediate. A second molecule of ATP is used to phosphorylate the carbamate intermediate to form carbamoyl phosphate. Carbamoyl phosphate synthetase I is the first committed step of the urea cycle. As one would expect this enzyme is allosterically regulated. This enzyme is allosterically activated by N-acetyl glutamate. N-acetylglutamate is a precursor for ornithine biosynthesis and is an essential activator for the urea cycle. N-acetyl glutamate also serves to coordinate related pathways. The carbamoyl phosphate formed by this reaction enters into the urea cycle as a substrate for ornithine transcarbamoylase which catalyzes the following

Ornthine is then transported back in the matrix of the mitochondria and the cycle is complete.

Importance of Urea Cycle:

The Urea Cycle - the Ornithine Cycle - is essentially the last part of Nitrogen metabolism in some organisms. When proteins are broken down, they are deaminated - the NH2 group is removed, and converted to NH3 (Ammonia). Ammonia is extremely toxic in small concentrations and so has to be removed quickly - some animals (e.g. Fish) can release it directly into their environment, as NH3 readily dissolves. This is not possible for animals in a land/air environment, as they need to conserve water, but they still need to remove the Ammonia.

In the Ornithine cycle, the Ammonia is converted to Urea – CO (NH2)2 - mostly in the Liver, which is far less toxic, and can be transported to the kidneys, filtered and removed dissolved in water as Urine. Some organisms take this a step further by converting the Ammonia to Uric Acid - these are animals which need to conserve the most water - birds, reptiles, and insects - though it is done by a different