Food Chemistry and Fish in Nutrition ( 2+1)

8.2.2.4Synthesis of Urea by urea cycle

Synthesis of Urea by urea cycle (Ornithine Cycle or Krebs – Henseleit Cycle)

 

            Urea is the major end product of nitrogen catabolism. Urea is formed from ammonia, carbon dioxide, and aspartate, synthesis of one mol each of ammonium ion and the a -amino nitrogen of aspartate. The synthesis of urea has several steps.

 

(i) Synthesis of carbamoyl phosphate:

            The biosynthesis of urea begins with the condensation of carbon dioxide, ammonia, and ATP to form carbamoyl phosphate, a reaction catalyzed by carbamoy1 phosphate synthase. Formation of carbamoy1 phosphate requires 2 mol of ATP.(Fig8.2.2).One ATP serves as a source of phosphate. Conversion of the second ATP to AMP and pyrophosphate, together with the coupled hydrolysis of pyrophosphate to orthophosphate, provides the driving force for synthesis of the amide bond and the mixed acid anhydride bond of carbamoy1 phosphate.

(ii) Synthesis of citrulline

            In the next step, carbamoy1 phosphate donates its carbamoy1 to ornithine to form citrulline and release phosphate in a reaction catalyzed by ornithine transcarbamoylase, a Mg2+ requiring enzyme. The citrulline thus formed leaves the mitochondria and passes into the cytosol of the liver cells.

 

 

 

(iii). Synthesis of Arginosuccinate

            The second amino group is introduced in the form of L asparate, which in turn acquired it form L. glutamate by the action of aspartate  transaminase. The transfer of the second amino group to citrulline occurs by a condensation reaction between the amino group of aspartate and the carbamoy1 carbon citrulline in the presence of ATP to form arginosuccinate, catalyzed by the enzyme arginosuccinate synthetase.

 

(iv) Action of  arginosuccinate lyase

            In the next step, arginosuccinate is reversibly cleaved by arginosuccinase to form free arginate and fumarate. The fumarate so formed returns to the pool of citric acid cycle intermediates.

 

(v) Action of arginase

 In the last reaction arginase cleaves arginate to yield urea and ornithine. Ornithine thus generated enters the mitochondria again to initiate another round of urea cycle. The overall equation of the urea cycle is

 

2NH4+  + HCO3- + 3ATP4- + H2O     →    Urea + 2ATP3- + 2Pi- + AMP- + PPi3- + H+

 

            The urea cycle brings together two amino and HCO3- to form a molecule of urea which diffuses from the liver cells into the blood thence to be excreted into the urine by the kidneys.

 

Thus the toxic ammonia is converted into harmless urea in ureotelic animals. Two molecules of ATP are required to make carbamoy1 phosphate and one is required to make arginosuccinate in which one molecule of ATP undergoes a pyrophosphate cleavage to AMP and pyrophophosphate, which may be hydrolyzed to yield two orthophosphates.

 

 The ultimate cost of one molecule of urea is four ATP molecules. The daily output of urea through urine is 20-30g. A less quantity is excreted through sweat. The excretion of urea is proportional to the total protein metabolism.