Why is ammonia dangerous?
What is ammonia? Ammonia is a metabolite that, in excess, becomes a neurotoxin.
It has the lowest molecular mass among all nitrogen-containing compounds of biological interest. Ammonia can move by simple diffusion—that is, free penetration. For example, from the gastrointestinal tract through the bloodstream to any other tissue, such as the brain.
Blood ammonia levels must remain very low, as even slightly elevated concentrations are toxic to the central nervous system (CNS).
Ammonia can significantly impair speech development and other abilities that are not prioritised for survival in children from birth and especially up to 3 years of age.
Ammonia increases epithelial permeability and induces tumour necrosis factor (TNF) expression. When ammonia accumulates, pH in cells rises to toxic levels, which can adversely affect metabolism.
Elevated ammonia levels have harmful effects on neutrophils, leading to impaired immunity. Accumulation of ammonia can lead to visual impairment.
About 90% of hyperammonaemic patients have liver disease. Toxic increases in ammonia levels are mainly linked to impaired liver detoxification, which can arise from genetic predisposition or acquired dysfunction. Impaired ammonia detoxification (urea cycle) can adversely affect the main metabolic system that takes place in the liver. As a result of excessive ammonia load (hyperammonaemia), hepatic encephalopathy can develop.
Acute hyperammonaemia causes rapidly progressive, often fatal encephalopathy with brain oedema. Chronic hyperammonaemia causes neuropsychiatric disorders. When hyperammonaemia occurs in a newborn, structural brain damage ensues. This is associated with glutamine accumulation, neuronal damage, and effects on neurochemistry, cerebral blood flow and electrolyte balance. Ammonia has not only a physical effect on tissues but also a biochemical effect at the cellular level. Ammonia greatly affects neurotransmitter balance, mitochondrial function (energy production) and promotes inflammation.
Sources of ammonia:
1) Food industry
Ammonium hydroxide is used in the food industry—it is one of the most commonly used preservatives. It is used today by thousands of manufacturers—most often in the production of meat and other foods that require preservation. Manufacturers claim that as long as you consume ammonia in small amounts, it will not pose a risk to your health.
So which foods can contain large amounts of ammonia? These include:
- meat,
- chocolate,
- cheeses,
- yoghurts,
- doughnuts, cakes, biscuits,
- peanut butter,
- products with E150c and E150d additives. E150c and E150d are used for caramel colouring (dough, beer, chocolate, biscuits, spirits and liqueurs, creams, crisps, etc.),
- products with E503 (ammonium carbonate). E503 is used instead of baking soda and yeast (biscuits, bagels, cakes and other baked goods).
2) Protein
We consume about 100 g of protein per day. In the stomach, hydrochloric acid breaks down proteins with the enzyme pepsin into peptides; then in the large intestine peptides are split into ever smaller molecules, down to amino acids. This process is carried out by enzymes. The resulting amino acids are then absorbed through the small intestinal epithelium via sodium ions (Na+) and transported into the blood.
Ammonia can be produced during the deamination of amino acids (an important process in our body).
The body can use protein to produce energy. The breakdown product—ammonia—enters the urea cycle to be converted into non-toxic urea and excreted from the body in urine.
3) Pathogenic flora
Gut microbiota imbalance leads to many adverse consequences. Many pathogenic microorganisms can "recover" ammonia from urea. Moreover, they can release chemicals that enhance the neurotoxic effect of ammonia.
4) Purine breakdown
Purines play an important role in mechanoreception (a mechanoreceptor is a sensory receptor responsible for receiving signals such as touch, vibration and pain). Purine receptors are located throughout the brain. A by-product of the purine cycle is ammonia.
5) Sulfation pathway
The sulfation pathway is very important in humans. The pathway starts with the conversion of homocysteine to cystathionine and ends with the formation of glutathione, taurine, sulfates and sulfites. By-products of these reactions are ammonia and hydrogen sulfide.
How is ammonia excreted from the body?
Ammonia is converted to urea by the urea cycle. Urea is the end product of protein metabolism.
Urea synthesis is a five-step process involving the enzymes:
- N-acetyl glutamate synthase,
- Carbamoyl phosphate synthase,
- Ornithine carbamoyltransferase,
- Argininosuccinate synthase,
- Argininosuccinate lyase,
- Arginase,
- Nitric oxide synthase.
The first two enzymes, N-acetyl glutamate synthase and carbamoyl phosphate synthase, are located and function in the mitochondria; another two in the cell cytosol. Genetic defects that disrupt the urea cycle can lead to type I and type II hyperammonaemia, acidosis and impairment of the Krebs cycle.
Genes associated with the urea cycle:
- NAGS – synthesis of N-acetyl glutamate,
- CPS I – synthesis of carbamoyl phosphate,
- OTC – synthesis of citrulline,
- ASS – synthesis of argininosuccinate,
- ASL – synthesis of arginine,
- ARG – synthesis of ornithine,
- NOS3 – synthesis of nitric oxides.