From a chemical point of view, ammonium (NH4) is the conjugate acid that belongs to the base ammonia (NH3). Ammonium is the most common breakdown product from amino acid metabolism.
What is ammonium?
Ammonium is a cation. In its chemical reactions, it resembles alkali metal ions and can form salts just like these ions. Examples of such salts are ammonium nitrate or ammonium chloride. In nature, however, ammonium is mainly formed during the decomposition of proteins. Bacterial decomposition of dead biomass also produces ammonium as an end product. Similar to ammonia, ammonium can also have a neurotoxic effect in the human body.
Function, effects, and roles
In the medical context, ammonia is often referred to as being present in the body. Basically, this is not so correct, because ammonia is present in the body almost only in the form of ammonium ions. Ammonia or ammonium plays a role in many metabolic processes. However, ammonium is particularly important in the formation and breakdown of amino acids. Glutamate is formed from ammonium and α-ketoglutarate by a chemical process. This process is also known as reductive amination. Glutamate is a so-called α-amino acid. It is also known as glutamic acid. By means of transamination, further non-essential amino acids can be produced from glutamic acid. The amino acids formed in this way perform numerous tasks in the body. For example, they are involved in the regulation of various metabolic processes or serve as a precursor of hormones. But glutamate is not only a precursor of other amino acids, it is also one of the most important excitatory neurotransmitters in the central nervous system (CNS). Neurotransmitters are biochemical messengers that transmit stimulus from one nerve cell to another nerve cell or from one nerve cell to a body cell. In addition, glutamic acid also serves as a precursor to γ-aminobutyric acid (GABA). This in turn is one of the most important inhibitory neurotransmitters in the central nervous system.
Formation, occurrence, properties, and optimal levels
The largest amounts of ammonium are formed during the breakdown of amino acids. For most amino acids, degradation to glutamate first occurs via the process of transamination. This in turn is cleaved into the parent substances ammonium and α-ketoglutarate. The main site of ammonium formation is the intestine. In the large intestine in particular, ammonium is released from undigested protein by bacterial action. This then enters the bloodstream via the intestinal mucosa. But ammonium is also produced in the muscles and kidneys. Since ammonium, like ammonia, has a toxic effect in larger quantities and cannot be completely converted back into new amino acids, the body must have a way of breaking down ammonium. The ammonium in the blood quickly reaches the liver via the portal circulation. This converts the toxic ammonium into the harmless urea. Urea is a white, crystalline solid that is excreted in the urine. The standard values for ammonium in blood serum are 27 to 90 µg/dl (micrograms per deciliter) or, in conventional units, 16 to 53 µmol/l (micromoles per liter).
Diseases and disorders
An increase in blood ammonium levels occurs primarily when liver function is disturbed. Then the toxic ammonium can no longer be converted into the nontoxic urea. The most common cause of such liver dysfunction is alcoholic cirrhosis. In cirrhosis, liver tissue perishes over a period of several years and/or undergoes connective tissue remodeling (fibrosis). As a result, the blood supply to the liver is disturbed. Particularly in the area of the portal vein, the blood backs up in front of the liver. This is also called portal hyptertension. Part of the blood from the unpaired abdominal organs then no longer flows initially through the liver for detoxification, but enters the systemic circulation directly. Even the blood that actually still passes through the liver can no longer be sufficiently detoxified due to the cell changes within the liver. The first symptoms of cirrhosis (e.g. icterus) are noticed quite late by those affected. If the increased ammonium levels cause damage to the brain, this is known as hepatic encephalopathy. Initially, this usually results in only a mild psychosyndrome. Often, the changes are initially noticed only by friends or relatives. Typical symptoms at this stage are lack of movement, tremor or muscle twitching.Later in the course of the disease, there may be a compulsive need to sleep, muscle wasting, trembling of the hands and unsteadiness of gait. Gradually, increasing confusion sets in. The most severe form of hepatic encephalopathy is hepatic coma. This is also known as hepatic decay coma or coma hepaticum. At this stage, patients are unconscious and cannot be awakened even with pain stimuli. Ammonium in the urine is always a sign of concrements. Concrements are crystalline deposits of the urinary tract. They are also called urinary calculi or uroliths. There are many different types of urinary calculi. Ammonium is part of the so-called struvites. These are magnesium ammonium phosphate. Urinary stones can have different causes. For example, inflammation of the kidneys or ureters can lead to the formation of urinary stones. Metabolic disorders such as gout, cystinuria or diabetes can also cause urinary stones. The stones often go unnoticed for a long time. Symptoms only develop when a stone becomes lodged in the renal pelvis or ureter. Extreme painful colics then occur. Small stones usually go away on their own; large stones must be surgically removed or crushed by shock waves.
