4. Ammonia detoxification and urea cycle.

The NH4+ resulting from deamination of amino acid (such as glutamate) is converted to ammonia either directly or indirectly.
In microorganisms, when need to dispose of, ammonia may be secreted directly into environment and carried away.
But to many animals, ammonia is toxic, and its removal by simple diffusion is difficult.
Uric acid is the major form of detoxified ammonia in nitrogen excretion in birds.
Urea is the principle end product of nitrogen metabolism which also help to maintain osmotic balance in many fishes.
First proposed in 1932, urea formation is a complex and costly (energy needed) mode of ammonia detoxification in the liver of mammals.
With the help from 5 enzymes, free ammonia formed by oxidative deamination of glutamate is converted into carbamoyl phosphate and then, finally into urea.
The urea formed in the liver cells is diffused into bloodstream and is ultimately eliminated through the kidneys in the urine.
The over-all reactions of the urea cycle is:
CO2 + NH4+ + 3 ATP + aspartate + 2 H2O --->
Urea + 2 ADP + 2 Pi + AMP + PPi + fumarate + 6 H+
In each cycle of urea cycle, 2 nitrogens are eliminated, one originating from the oxidative deamination of glutamate and the other coming from the a-amino group of aspartate.
It will take the equivalent of 4 high-energy phosphates to form a single molecule of urea.
Urea cycle is linked to TCA cycle.
Glutamine and alanine are also carriers of ammonia (from muscle and other tissues to liver) 
  • Glutamine synthetase and its role in amino acid synthesis 
  • Glutaminase 
  • Other roles of glutamine 
  • Glucose-alanine cycle and pyruvate (in contracting muscle) 


1,2    3       5    6    7
I    Back