Reactions of Urea Cycle | Protein Metabolism

The below mentioned article provides a short note on the Reactions of Urea Cycle.

Carbamoyl phosphate is formed by the condensation of one mol of phosphate (derived from ATP) being catalyzed by the enzyme carbamoyl phosphate synthetase which is present in liver mitochondria of all ureotelic organisms including humans.

In addition to magnesium ion (Mg⁺⁺), N-acetyl-glutamate (a dicarboxylic acid) is required. Probably, the presence of N-acetyl-glutamate brings about a marked change in the structure of carbamoyl phos­phate synthetase which exposes certain sulfhydryl groups and affects the affin­ity of the enzyme for ATP.

In bacteria, glutamine in place of ammo­nia serves as a substrate for carbamoyl phosphate synthesis.

Carbamoyl moiety is transferred to orni­thine to form citrulline being catalyzed by ornithine transcarbamoylase of liver mitochondria.

Arginosuccinic acid is formed by the com­bination of citrulline and aspartic acid in presence of arginosuccinic acid synthetase and ATP.

Arginosuccinic acid is cleaved to arginine and fumaric acid by arginosuccinase which is present in mammalian liver and kidney. The fumarate formed is converted to oxaloacetate via the fumarase and malate dehydrogenase reactions and then trans-aminated to regenerate aspartate.

The hydrolytic cleavage of arginine is catalyzed by arginase which is present in the livers of all ureotelic organisms form­ing ornithine and urea.

Smaller quantities of arginase also occur in renal tissue, brain, mammary gland, tes­ticular tissue and skin. Ornithine and lysine are the competitive inhibitors of arginine.

The cycle for the overall reactions is given in Fig. 20.7.

The biosynthesis of urea occurs mainly in the liver. 1 mol of urea is synthesized from 1 mol of ammonia, 1 mol of carbon dioxide, 3 mols of ATP (2 of which are converted to ADP and Pi and 1 to AMP + PPi), 5 enzymes catalyzing the reactions and 6 amino acids involved in the reaction.

One amino acid, N-acetyl-glutamate, serves as an enzyme activator. The remaining 5 amino acids aspartate, arginine, ornithine, citrulline and arginosuccinic acid – all function as carriers of at­oms which, ultimately, become urea. Aspartate and arginine occur in protein while ornithine, citrul­line, arginosuccinate do not.

Urea formation is partly a cyclical process. Ornithine used in reaction (2) is regenerated in re­action (5).

An active man consuming about 300g of car­bohydrates, 100g of fat, 100g of protein daily ex­crete about 16.5g of nitrogen. 95 per cent is elimi­nated by the kidneys and 5 per cent in the Stool. The major pathway of nitrogen excretion in hu­mans is as urea which is synthesized in the liver.

Blood Level:

Normal concentration of urea in the blood is 15 to 45 mg/100 ml.

Excretion:

The daily output of urea through urine is 20 to 30 grams. A less quantity is excreted in the sweat. The quantity of urea excreted is pro­portional to the total protein metabolism.

The ex­cretion of urea is decreased in certain liver diseases. In severe acidosis, the output of urea is decreased. In nephritis, when the ability of the kidneys to ex­crete urea is severely impaired, the concentration of urea in the blood is increased (uremia).