Formation and detoxification of ammonia, urea cycle and its regulation, hyperammonaemia
Ammonia-NH3 synthesis[edit | edit source]
Ammonia-NH3 is a toxic weak basic compound that needs to be detoxified and eliminated from the body. Ammonia derives from the metabolism of amino acids and especially that of gluconeogenesic transversion of amino acid into glucose. Glucose can be synthesized from amino acid carbon skeleton after the removal of its amino group. This removal of the amino group occurs through two similar processes, transamination and deamination.
Urea cycle[edit | edit source]
Ammonia detoxification[edit | edit source]
Ammonia is rapidly removed from the circulation in the liver, converted into a water soluble compound known as urea. Ammonia is toxic to the CNS because it reacts with the α-ketoglutarate to form glutamate. As a consequence, the depleted levels of α-ketoglutarate impairs the function of the Citric Acid cycle in neurons, depriving them energy production. Furthermore, glutamate is a potent CNS neurotransmitter, thus any significant increase in the concentration of glutamate could have abnormal effects in synaptic transmission.
|1||NH4+ + HCO3− + 2ATP||Carbamoyl phosphate + 2ADP + Pi||Carbamoyl phosphate synthetase I||mitochondria|
|2||Carbamoyl phosphate + Ornithine||Citrulline + Pi||Ornithine transcarbamoylase||mitochondria|
|3||Citrulline + Aspartate + ATP||Argininosuccinate + AMP + pyrophosphate||Argininosuccinate synthetase||cytosol|
|4||Argininosuccinate||Arginine + Fumarate||Argininosuccinase||cytosol|
|5||Arg + H2O||Ornithine + Urea||Arginase||cytosol|
Urea cycle regulation[edit | edit source]
Urea cycle is regulated by the rate limiting enzyme carbamoyl phosphate synthase I, the first enzyme of the ammonia detoxification pathway. It is only active in presence of its allosteric activator N-methyl-glutamate amino acid. It catalyses the condensation of ammonium ions NH4+, CO2 and ATP to form carbamoyl phosphate, a product that will condense with L-ornithine in order to initiate the urea cycle.
Links[edit | edit source]
Bibliography[edit | edit source]
MURRAY, Robert K. – BENDER, David A.. Harper's Illustrated Biochemistry. 29th edition. McGraw-Hill Companies, Inc., 2012. ISBN 978-0-07-176576-3.