Ornithine cycle: reactions, pattern, description, metabolic disorders

In order for the human body to maintain normal life activity, it has developed mechanisms for the removal of toxic substances. Among them, ammonia is the final product of the metabolism of nitrogen compounds, especially proteins. NH ₃ is toxic to the body, and, like any poison, is excreted through the excretory system. But before ammonia undergoes a series of successive reactions, which is called the ornithine cycle.

Types of nitrogen metabolism

Not all animals are characterized by the release of ammonia into the environment. Alternative final substances of nitrogen metabolism are uric acid and urea. Accordingly, there are three types of nitrogen metabolism, depending on the substance released.

Ammonothelic type. The final substance here is ammonia. It is a colorless gas, soluble in water. Ammoniothelia is characteristic of all fish that live in salt water bodies.

Ureothelic type. Animals, which are characterized by ureothelium, release urea into the environment. Examples are freshwater fish, amphibians and mammals, including humans.

Urinary type. These include those representatives of the animal world, in which the final metabolite is the crystals of uric acid. This substance as a product of nitrogen metabolism is found in birds and reptiles.

In any of these cases, the task of the final product of metabolism is the removal of unnecessary nitrogen from the body. If this does not happen, cell valuation and inhibition of important reactions are observed.

What is urea?

Urea is an amide of carbonic acid. It is formed from ammonia, carbon dioxide, nitrogen and amino groups of some substances during the course of reactions of the ornithine cycle. Urea is the product of the isolation of ureothelic animals, including man.

Urea is one way of excreting excess nitrogen from the body. The formation of this substance carries a protective function, t. The precursor of urea is ammonia, it is toxic to human cells.

When processing 100 g of protein of different nature with urine, 20-25 g of urea is released. The substance is synthesized in the liver, and then with blood flow enters the nephron of the kidney and is excreted along with the urine.

The liver is the main organ of urea synthesis

In the entire human body there is no such cell in which absolutely all enzymes of the ornithine cycle will be present. Except hepatocytes, of course. The function of liver cells is not only in the synthesis and destruction of hemoglobin, but also in carrying out all the reactions of urea synthesis.

The description of the ornithine cycle is suitable for the fact that it is the only way to remove nitrogen from the body. If in practice to inhibit the synthesis or action of the main enzymes, the synthesis of urea will stop, and the body will die from an overabundance of ammonia in the blood.

Ornithine cycle. Biochemistry of reactions

The cycle of urea synthesis takes place in several stages. The general scheme of the ornithine cycle is presented below (picture), so we will analyze each reaction separately. The first two stages proceed directly in the mitochondria of the liver cells.

NH ₃ reacts with carbon dioxide with the cost of two ATP molecules. As a result of this energy-consuming reaction, carbamoyl phosphate is formed, which contains a macroergic bond. The enzyme carbamoyl phosphate synthetase catalyzes this process.

Carbamoyl phosphate reacts with ornithine under the action of the enzyme ornithine-carbamoyl transferase. As a result, the macroergic bond is destroyed, and at the expense of its energy, citrulline is formed.

The third and subsequent stages proceed not in mitochondria, but in the cytoplasm of hepatocytes.

There is a reaction between citrulline and asparagus. With the expenditure of 1 ATP molecule and the action of the arginine-succinate synthase enzyme, arginine succinate is formed.

Arginine-succinate in combination with the enzyme arginine-succine-lyase is split into arginine and fumarate.

Arginine in the presence of water and under the action of arginase is split into ornithine (1 reaction) and urea (final product). The cycle is closed.

Energy of the urea synthesis cycle

The ornithine cycle is an energy-consuming process in which macroergic bonds of adenosine triphosphate molecules (ATP) are consumed. Throughout the 5 reactions in the aggregate, 3 molecules of ADP are formed. In addition, energy is spent on the transport of substances from the mitochondria to the cytoplasm and vice versa. Where does the ATP come from?

Fumarate, which was formed in the fourth reaction, can be used as a substrate in a cycle of tricarboxylic acids. During the synthesis of malate from fumarate, NADPH is released, which results in 3 molecules of ATP.

The deamination of glutamate also plays a role in supplying the liver cells with energy. At the same time, 3 molecules of ATP are also isolated, which go to the synthesis of urea.

Regulation of ornithine cycle activity

Normally, the cascade of urea synthesis reactions functions at 60% of the possible value. With an increased protein content in food, reactions accelerate, which leads to an increase in overall efficiency. Metabolic disorders of the ornithine cycle are observed with high physical loads and prolonged starvation, when the body begins to break down its own proteins.

Regulation of the ornithine cycle can also occur at the biochemical level. Here the main enzyme is carbamoyl phosphate synthetase. Its allosteric activator is N-acetyl-glutamate. With its high content in the body, the urea synthesis reactions proceed normally. With a lack of the substance itself or its precursors, glutamate and acetyl-CoA, the ornithine cycle loses its functional load.

The connection between the urea synthesis cycle and the Krebs cycle

The reactions of both processes occur in the mitochondrial matrix. This makes it possible to participate in some organic substances in two biochemical processes.

CO ₂ and adenosine triphosphate, which are formed in the cycle of citric acid, are precursors of carbamoyl phosphate. ATP is also an important source of energy.

Ornithine cycle, the reactions of which occur in hepatocytes of the liver, is the source of fumarate, one of the most important substrates in the Krebs cycle. Moreover, this substance, as a result of several stepwise reactions, gives rise to aspartate, which, in turn, is used in the biosynthesis of the ornithine cycle. The reaction involving fumarate is a source of NADP, with which it is possible to phosphorylate ADP to ATP.

The biological meaning of the ornithine cycle

The vast majority of nitrogen enters the body as a part of proteins. In the process of metabolism, amino acids are destroyed, ammonia is formed as the final product of metabolic processes. The ornithine cycle is a series of successive reactions whose main task is to detoxify NH ₃ by means of its transfer to urea. Urea, in turn, enters the kidney nephron and is excreted from the body with urine.

In addition, the side-by-side ornithine cycle is the source of arginine, one of the essential amino acids.

Disorders in the synthesis of urea can lead to a disease such as hyperammonemia. This pathology is characterized by an increased concentration of ammonium NH _{4 ⁺} ions in human blood. These ions adversely affect the life of the organism, turning off or slowing down some important processes. Ignoring this disease can lead to death.