In order for the human body to maintain normal life, it has developed mechanisms for the elimination of toxic substances. Among them, ammonia is the end product of the metabolism of nitrogenous compounds, primarily proteins. NH3 is toxic to the body and, like any poison, is eliminated 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 release ammonia into the environment. Alternative end substances of nitrogen metabolism are uric acid and urea. Accordingly, three types of nitrogen metabolism are called, depending on the substance released.
Ammoniotelic type. The end product here is ammonia. It is a colorless gas soluble in water. Ammoniothelia is characteristic of all fish that live in s alt water.
Ureotelic type. Animals that are characterized by ureothelia release urea into the environment. Examples arefreshwater fish, amphibians and mammals, including humans.
Uricotelic type. This includes those representatives of the animal world, in which the final metabolite is uric acid crystals. This substance as a product of nitrogen metabolism is found in birds and reptiles.
In any of these cases, the task of the end product of metabolism is to remove unnecessary nitrogen from the body. If this does not happen, 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 reactions of the ornithine cycle. Urea is a waste product of ureotelic animals, including humans.
Urea is one way to excrete 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, 20-25 g of urea is excreted in the urine. The substance is synthesized in the liver, and then with the blood flow enters the nephron of the kidney and is excreted along with the urine.
The liver is the main organ for the synthesis of urea
In the whole human body there is no such cell in which absolutely all the enzymes of the ornithine cycle will be present. Except for hepatocytes, of course. The function of liver cells is not only to synthesize and destroy hemoglobin, but also to carry out all reactions of urea synthesis.
UnderThe description of the ornithine cycle fits the fact that it is the only way to remove nitrogen from the body. If in practice the synthesis or action of the main enzymes is inhibited, 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), so we will analyze each reaction separately. The first two stages take place directly in the mitochondria of liver cells.
NH3 reacts with carbon dioxide using two ATP molecules. As a result of this energy-consuming reaction, carbamoyl phosphate is formed, which contains a macroergic bond. This process is catalyzed by the enzyme carbamoyl phosphate synthetase.
Carbamoyl phosphate reacts with ornithine by the enzyme ornithine carbamoyl transferase. As a result, the high-energy bond is destroyed, and citrulline is formed due to its energy.
The third and subsequent stages take place not in mitochondria, but in the cytoplasm of hepatocytes.
There is a reaction between citrulline and aspartate. With the consumption of 1 ATP molecule and under the action of the enzyme arginine-succinate synthase, arginine-succinate is formed.
Arginino-succinate, in combination with the enzyme arginino-succin-lyase, breaks down to arginine and fumarate.
Arginine in the presence of water and under the action of arginase is broken down to ornithine (1 reaction) and urea (final product). The cycle is complete.
Energy of the urea synthesis cycle
The ornithine cycle is an energy-consuming process in which macroergic bonds of adenosine triphosphate (ATP) molecules are consumed. During all 5 reactions, 3 ADP molecules are formed in total. In addition, energy is spent on the transport of substances from the mitochondria to the cytoplasm and vice versa. Where does ATP come from?
Fumarate, which was formed in the fourth reaction, can be used as a substrate in the tricarboxylic acid cycle. During the synthesis of malate from fumarate, NADPH is released, which results in 3 ATP molecules.
Glutamate deamination reaction also plays a role in supplying liver cells with energy. At the same time, 3 ATP molecules are also released, which are used for the synthesis of urea.
Regulation of ornithine cycle activity
Normally, the cascade of urea synthesis reactions functions at 60% of its possible value. With an increased protein content in food, reactions are accelerated, which leads to an increase in overall efficiency. Metabolic disorders of the ornithine cycle are observed during high physical exertion and prolonged fasting, when the body begins to break down its own proteins.
The regulation of the ornithine cycle can also occur at the biochemical level. Here 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 lack of the substance itself or itsprecursors, glutamate and acetyl-CoA, the ornithine cycle loses its functional load.
Relationship between the urea synthesis cycle and the Krebs cycle
The reactions of both processes take place in the mitochondrial matrix. This makes it possible for some organic substances to participate in two biochemical processes.
CO2 and adenosine triphosphate, which are formed in the citric acid cycle, are precursors of carbamoyl phosphate. ATP is also the most important source of energy.
The ornithine cycle, whose reactions take place in liver hepatocytes, is a 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 fumarate reaction is a source of NADP, which can be used to phosphorylate ADP to ATP.
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 end product of metabolic processes. The ornithine cycle consists of several consecutive reactions, the main task of which is to detoxify NH3 by converting it into urea. Urea, in turn, enters the nephron of the kidney and is excreted from the body with urine.
In addition, by-product of the ornithine cycle is a source of arginine, one of the essential amino acids.
Violations in synthesisurea can lead to a disease such as hyperammonemia. This pathology is characterized by an increased concentration of ammonium ions NH4+ in human blood. These ions adversely affect the life of the body, turning off or slowing down some important processes. Ignoring this disease can lead to death.
