Nitrogenous Waste, Urea cycle and Formation of uric acid

Ammonia is a toxic product to the body of animals, thus ammonia is continuously excreted from the body of the animals, in various from depending upon the external environment and physiology of animals.

Nitrogenous Waste, Urea cycle and Formation of uric acid

Types of animal-based on excretion of nitrogenous waste

There are different types of nitrogenous waste products in different types of animals, animals are categorized into groups based on the type of nitrogenous waste they excrete. Animals have the following types of nitrogenous excretion-

Aminotelic animals

Some exceptional organisms directly excrete amino-acid, known as aminotelic.

Ammonotelic animals

Most aquatic species as like bony fishes excrete ammonia. Ammonia is a toxic compound simply diluted into the surrounding water. And terrestrial organisms do not have a surrounding water environment, so can’t excrete nitrogenous waste in form of ammonia.

Ureotelic animals

Terrestrial amphibians, cartilaginous fish, some bony fish, and mammals are ureotelic. Their excretory product is urea, in these organisms, toxic ammonia is converted into urea, and urea is excreted with water in a dissolved form called urine.

Uricotelic animals

Reptiles and birds are uricotelic. They have to conserve water and do not excrete much water in form of urine. So they excrete semi-solid excretory product uric acid.

Urea cycle (formation of urea)

The urea cycle takes place in 5 successive enzymatic steps, beginning two steps take place mitochondria of liver cells, and the rest three steps take place inside the cytosol, thus the urea cycle is completed in two compartments. The amino group that enters into the urea cycle is from ammonia of the mitochondrial matrix, which arises during the breakdown process.

Step-I, synthesis of carbamoyl phosphate

Ammonia is changed into carbamoyl phosphate after combining with carbonate and phosphate from ATP, in the presence of carbamoyl phosphate synthetase I.

Step-II, formation of citrulline

Carbamoyl phosphate synthesizes in the previous step now donate carbamoyl group to ornithine in presence of ornithine transcarbamoylase enzyme to form citrulline.

Step-III, formation of arginosuccinate

This step takes place in the cytosol. Citrulline synthesized in the previous step is transported to cytosol, and aspartate, which is synthesized by transamination of oxaloacetate is also transported to the cytosol from the mitochondria. This reaction is taking place in presence of argininosuccinate synthetase which requires ATP and forms citrullyl-AMP intermediate, now aspartate and citrulline from citrullyl-AMP intermediate join to each other by amino group of aspartate and carbamoyl group of citrulline forming the argininosuccinate.

Step-IV, cleavage of argininosuccinate

In this step, argininosuccinate is cleaved by argininosuccinase enzyme to form arginine and fumarate. This fumarate changes into malate and enters into mitochondria and joins the pool of citric acid cycle, hence, oxaloacetate of the citric acid cycle which is transaminated to form aspartate for urea cycle, recycled, this shunt is called as aspartate arginosuccinate shunt. And the arginine enters the next step of the urea cycle.

Step-V, cleavage of arginine

In the fifth and last step of the urea, cycle arginine is cleaved into ornithine and urea. Now this ornithine is transported to mitochondria to initiate a new round of the urea cycle.

urea cycle

Figure- Reactions of the urea cycle. Image Source: Lippincott’s Illustrated Reviews: Biochemistry. Seventh Edition.

Formation of uric acid

Uric acid is generated by the breakdown of nucleotides, mainly from purines nucleotides. Purine nucleotides such as Adenosine-nucleotide and Guanosine-nucleotide breakdown produce uric acid. The process takes place in two ways-

Uric acid production from Adenosine-nucleotide

Breakdown or catabolism of Adenosine nucleotide produces uric acid. This breakdown process takes place in following successive step are as follow –

Step I

The enzyme namely 5’nucleotidase removes one inorganic phosphate from AMP in presence of water and converts it into Adenosine.

Step II

In this step adenosine deaminase remove NH3 by use of water, thus convert adenosine to inosine, which is also a purine nucleoside like adenosine.

Step III

Now inosine is breakdown into ribose and hypoxanthine in presence of nucleosidase enzyme and water.

Step IV

Now hypoxanthine is converted into xanthine, the reaction is catalyzed by xanthine oxidase enzyme in presence of water, & oxygen and hydrogen peroxide is librated.

Step V

In this reaction, xanthine is converted into uric acid, as in the previous reaction this reaction is also catalyzed by xanthine oxidase enzyme in presence of water & oxygen and hydrogen peroxide is librated.

Uric acid production from Guanosine-nucleotide

Breakdown of guanosine nucleotide (GMP) produces uric acid, this is catalyzed in several steps.

Step I

This step is like the first step of uric acid production from adenosine-nucleotide. Here also enzyme 5’nucleotidase removes one inorganic phosphate from GMP in presence of water and converts it into guanosine.

Step II

Now nucleosidase break guanosine into guanine and ribose in presence of water.

Step III

In this step guanine is converted into xanthine by removal of NH3 in presence of water, this reaction is catalyzed by guanine deaminase.

Step IV

Now xanthine oxidase converts xanthine into uric acid, in presence of water, & oxygen, and hydrogen peroxide is librated. This step is the same as the last step of uric acid production from adenosine-nucleotide.

References and Sources

  1. Lehninger principle of biochemistry by David L. Nelson and Michael M. Cox.
  2. (Physiology, Urea Cycle – StatPearls – NCBI Bookshelf)
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