In order for the human body to maintain normal life activity, he has developed mechanisms for eliminating toxic substances. Among them, ammonia is the end product of the metabolism of nitrogenous compounds, primarily 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 sequential reactions, which is called the ornithine cycle.
Types of Nitrogen Exchange
Not all animals are characterized by the release of ammonia into the environment. Alternative end substances for nitrogen metabolism are uric acid and urea. Accordingly, three types of nitrogen metabolism are called, depending on the substance released.
Ammoniothelic type. The final substance here is ammonia. It is a colorless gas soluble in water. Ammoniothelium is characteristic of all fish that live in salt bodies of water.
Ureotelic type. Animals that are characterized by ureothelium release urea into the environment. Examples are freshwater fish, amphibians, and mammals, including humans.
Uricothelic type. This includes those representatives of the animal world in which uric acid crystals are the final metabolite . This substance as a product of nitrogen metabolism is found in birds and reptiles.
In any of these cases, the goal of the final metabolic product is the removal of unnecessary nitrogen from the body. If this does not occur, cell taxation 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 certain substances during the course of reactions of the ornithine cycle. Urea is a product of the release of ureotelic animals, including humans.
Urea is one way of excreting excess nitrogen from the body. The formation of this substance has a protective function, because urea precursor - ammonia, toxic to human cells.
When processing 100 g of protein of various nature with urine, 20-25 g of urea is released. The substance is synthesized in the liver, and after a blood stream enters the kidney nephron and is excreted in the urine.
The liver is the main organ of urea synthesis
Throughout the human body there is no such cell in which absolutely all the enzymes of the ornithine cycle will be present. In addition to hepatocytes, of course. The function of liver cells consists not only in the synthesis and destruction of hemoglobin, but also in the conduct of all urea synthesis reactions.
The fact that it is the only way to remove nitrogen from the body fits the description of the ornithine cycle. If, in practice, inhibit the synthesis or action of major enzymes, the synthesis of urea will stop, and the body will die from an excess of ammonia in the blood.
Ornithine cycle. Biochemistry of reactions
The urea synthesis cycle takes place in several stages. The general scheme of the ornithine cycle is presented below (picture), therefore, 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 at the expense of two ATP molecules. As a result of this energy-intensive reaction, carbamoyl phosphate is formed, which contains a macroergic bond. The enzyme carbamoyl phosphate synthetase catalyzes this process.
Carbamoyl phosphate reacts with ornithine by the action of the ornithine-carbamoyl transferase enzyme. As a result, the macroergic bond is destroyed, and citrulline is formed due to its energy.
The third and subsequent stages proceed not in the mitochondria, but in the cytoplasm of hepatocytes.
There is a reaction between citrulline and asparagus. With the consumption of 1 ATP molecule and under the action of the enzyme arginine-succinate synthase, arginine-succinate is formed.
Arginine-succinate in combination with the enzyme arginine-succin-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.
Urea synthesis cycle energy
The ornithine cycle is an energy-consuming process in which macroergic bonds of adenosine triphosphate (ATP) molecules are consumed. Over the course of all 5 reactions, 3 ADP molecules are formed in aggregate. In addition, energy is spent on the transport of substances from the mitochondria to the cytoplasm and vice versa. Where does ATP come from?
The fumarate, which was formed in the fourth reaction, can be used as a substrate in the tricarboxylic acid cycle. During the synthesis of malate, NADPH is released from the fumarate, which results in 3 ATP molecules.
The glutamate deamination reaction also plays a role in supplying liver cells with energy. At the same time, 3 ATP molecules are also released that are used for urea synthesis.
Regulation of the activity of the ornithine cycle
Normally, the cascade of urea synthesis reactions functions at 60% of the possible value. With a high content of protein in food, reactions accelerate, which leads to an increase in overall efficiency. Metabolic disorders of the ornithine cycle are observed with high physical exertion and prolonged starvation, when the body begins to break down its own proteins.
Regulation of the ornithine cycle can occur at the biochemical level. The target is the main enzyme, carbamoyl phosphate synthetase. Its allosteric activator is N-acetyl-glutamate. With its high content in the body, urea synthesis reactions proceed normally. With a deficiency 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 proceed in the matrix of mitochondria. This makes it possible for some organic substances to participate in two biochemical processes.
CO 2 and adenosine triphosphate, which are formed in the citric acid cycle, are precursors of carbamoyl phosphate. ATP is also an essential energy source.
The ornithine cycle, the reactions of which occur in the hepatocytes of the liver, is a source of fumarate, one of the most important substrates in the Krebs cycle. Moreover, as a result of several phased reactions, this substance gives rise to aspartate, which, in turn, is used in the biosynthesis of the ornithine cycle. The fumarate reaction is a source of NADP, with which you can phosphorylate ADP to ATP.
The biological meaning of the ornithine cycle
The vast majority of nitrogen enters the body as 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 sequential reactions whose main task is to detoxify NH 3 by transferring it to urea. Urea, in turn, enters the kidney nephron and is excreted in the urine.
In addition, the ornithine cycle is a source of arginine, one of the essential amino acids.
Violations in the synthesis of urea can lead to a disease such as hyperammonemia. This pathology is characterized by an increased concentration of ammonium ions NH 4 + in human blood. These ions negatively affect the life of the body, turning off or slowing down some important processes. Ignoring this disease can be fatal.