Methionine plays the role in metabolism as a supplier of methyl groups (CH3), which are required for essential biosyntheses. To perform this function, the essential amino acid must first be activated with ATP (adenosine triphosphate). The reaction steps of methionine activation are catalyzed by methionine adenosyl transferase. As a result of the cleavage of triphosphate, energy is released that the transferase requires for the transfer of the adenosine residue to methionine. S-adenosylmethionine, or SAM for short, is formed. S-adenosylmethionine is the metabolically active form of methionine. Due to the highly reactive methyl group on the sulfonium group, S-adenosylmethionine is able to initiate transmethylation processes catalyzed by the enzyme methyltransferase. Consequently, SAM is both a substrate and a methyl group donor for methyltransferase. In a first step, SAM transports the methyl group to the methyltransferase, which in a second step transfers the CH3 residue to specific substrates, which in this way undergo structural changes. In intermediary metabolism, transmethylations are important reactions in the biosynthesis of the following endogenous substances.
- Adrenaline, a hormone formed in the adrenal medulla and secreted into the blood during stressful situations, which is formed from norepinephrine by transfer of a methyl group; as a catecholamine, adrenaline has a stimulatory effect at the sympathetic alpha and beta receptors of the cardiovascular system – it increases blood pressure and increases heart rate; in the central nervous system, adrenaline acts as a neurotransmitter – messenger or transmitter substance – and is thus responsible for the transmission of information from one neuron (nerve cells) to the next via the contact points of the neurons, the synapses
- Choline – is synthesized from ethanolamine by CH3 group transfer; as a primary monohydric alcohol, choline is a structural element of both the neurotransmitter acetylcholine – acetic acid ester of choline – and lecithin and phosphatidylcholine, respectively – phosphoric acid ester of choline – which is an essential component of all biomembranes; in addition, choline also acts as a methyl group donor in intermediary metabolism; in the case of methionine deficiency, insufficient amounts of choline are available for the synthesis of the important neurotransmitter acetylcholine – a long-term deficit of methionine can eventually cause anxiety and depression.
- Creatine, an organic acid formed as a result of transmethylation from guanidinoacetate; in the form of creatine phosphate, creatine is needed for muscle contraction and contributes to the supply of energy to the muscles.
- Nucleic acids – in the form of RNA (ribonucleic acid) and DNA (deoxyribonucleic acid), which serves as a carrier of genetic information.
- Polyamines – putrescine and decarboxylated SAM give rise to spermine and, as an intermediate, spermidine; both polyamines play a crucial role in cell division and help growing cells synthesize nucleic acids and proteins – consequently, polyamines have a stabilizing effect on DNA.The polyamine spermidine may increase intestinal health and thus contribute to improved immunity. Studies in cell as well as animal models show that dietary spermidine favors the differentiation of T helper cells towards regulatory T cells (Tregs).
- Glutathione – L-glutamyl-L-cysteinylglycine, GSH for short – a tripeptide formed from the amino acids glutamic acid, cysteine and glycine; as a substrate of glutathione peroxidase, GSH has antioxidant activity and protects cells, DNA and other macromolecules from oxidative damage, for example, radiation damage.
- L-carnitine – methionine together with lysine leads to the formation of L-carnitine, which plays a key role in the regulation of fat, carbohydrate and protein metabolism.
- Melatonin – a hormone that controls the day-night rhythm of the human body; it is formed from the methylation of N-acetylserotonin.
- Methylated pharmacone – detoxification of drugs.
- Methylated nucleic bases of DNA and RNA – protection of DNA from degradation.
DNA methylation
S-adenosylmethionine is essential for DNA methylation.In this process, the CH3 groups supplied by SAM are transferred to specific sites within the double-stranded DNA with the aid of DNA methyltransferases on nucleic bases such as adenine, guanine, cytosine and thymine. This is therefore a DNA modification or a chemical change in the basic structure of the DNA. Since DNA methylation does not lead to a change in the DNA sequence – the sequence of DNA building blocks – it is the subject of epigenetics or epigenetic inheritance. Epigenetics is the transmission of traits to offspring based on heritable changes in gene regulation and expression, rather than deviations in the DNA sequence. Epigenetic changes can be initiated by chemical or physical environmental factors. The DNA regions of particular importance for methylation are called CpG islands. In these DNA segments, the dinucleotide cytosine-guanine is present at ten to twenty times the frequency of the rest of the genome. In human genetic research, CpG islands are often used to assign genes to genetic diseases. DNA methylation has multiple biological functions. In prokaryotes, DNA methylation provides protection against foreign DNA. The DNA methyltransferases responsible for methylation lead to the formation of a methylation pattern by transferring CH3 groups to defined nucleic bases of the cell’s own DNA. Based on this methylation pattern, restriction enzymes are able to distinguish cell-own DNA from DNA that has entered the cell from outside. Foreign DNA usually has a different methylation pattern than the cell’s own DNA. If foreign DNA is recognized, it is cut and eliminated by restriction enzymes and other nucleases so that the foreign DNA cannot be integrated into the cell’s own DNA. Furthermore, DNA methylation is beneficial to prokaryotes for error correction during DNA replication – identical duplication of DNA. To distinguish the original DNA strand from the newly synthesized strand during error correction, DNA repair systems use the methylation pattern of the original strand. In eukaryotes, DNA methylation has the function of marking active and inactive regions of DNA. In this way, on the one hand, certain DNA segments can be selectively used for different processes. On the other hand, methylation silences or inactivates genes. For RNA polymerases and other enzymes, methylated nucleic bases on DNA or RNA are a sign that they should not be read for protein biosynthesis. DNA methylations ultimately serve to prevent the formation of defective, pathogenic proteins or to abort their synthesis. Some genes are selectively methylated, which is referred to as gene regulation or differential gene expression. Areas upstream of a gene may have a specific level of methylation that is distinct from the surrounding area and may vary in different situations. This allows for selective reading frequency of the gene behind it. An example of selectively methylated sites located upstream of a gene are the CpG islands. Since these are subject to high mutational pressure, methylation as a mechanism for silencing tumor suppressor genes is of paramount importance in preventing tumor diseases. If methylation is suppressed, the cytosines of the CpG islands can be oxidatively deaminated to thymine and uracil, respectively, due to their instability. This leads to base exchange and thus to a permanent mutation that significantly increases tumor risk. A special case of gene regulation is genomic imprinting. Since male and female germ cells have different DNA methylation patterns, paternal alleles can be distinguished from maternal alleles. In the case of genes subject to imprinting, only the maternal or paternal allele is used, which enables the sex-specific expression of phenotypic traits. Excessive or insufficient methylation of upstream DNA regions can lead to the development of diseases due to the resulting reduced or increased gene activity and inheritance to the daughter cells. For example, tumor cells often show methylation patterns that differ significantly from those of healthy tissues.In addition to individual nucleic bases in DNA, proteins and enzymes can also be modified by methyltransferases. Thus, the transfer of a methyl group to enzymes leads to a change in their properties, whereby the enzyme activity can either be inhibited or promoted.
Degradation and resynthesis of methionine – the methionine cycle
Of particular importance, both for human metabolism and for clinical practice, is the degradation of methionine. The essential amino acid methionine ingested with food is degraded to S-adenosylmethionine with the participation of ATP. As a result of the cleavage of the methyl group, which is taken up by methyltransferase and transferred to other substrates, the intermediate S-adenosylhomocysteine (SAH) is formed from SAM, which is hydrolyzed by SAH hydrolase to homocysteine and adenosine. Since SAH inhibits methylation processes, its degradation to homocysteine is urgently needed to maintain methylation reactions. The sulfur-containing, non-proteinogenic amino acid homocysteine, which is the result of the methionine cycle, can be catabolized in several ways. On the one hand, homocysteine is degraded via the process of transsulfation with the formation of the sulfur-containing amino acid cysteine. On the other hand, homocysteine can be metabolized by a remethylation reaction. Remethylation of homocysteine leads to the resynthesis of methionine. In the process of transsulfation, methionine reacts in a first step with serine via the vitamin B6-dependent cystathionine ß-synthase to form cystathionine with cleavage of homocystine. Cystathionine is cleaved in a second step to homoserine and the sulfur-containing amino acid cysteine. This reaction is catalyzed by cystathionase, which is also vitamin B6-dependent. Thus, when sulfur-containing methionine is broken down, the other sulfur-containing amino acid cysteine is formed, whereas serine is consumed. Cysteine can either be degraded in catabolic amino acid metabolism to sulfate and water, or lead to the synthesis of cystine by reaction with another cysteine molecule. In addition, the cysteine molecule serves as the starting building block for the formation of taurine, a ß-aminoethanesulfonic acid that carries a sulfonic acid group instead of a carboxyl group typical of amino acids. Taurine is not used in the body for protein biosynthesis, but is largely responsible for stabilizing the fluid balance in the cells. If the intake of methionine is too low, the synthesis of cysteine from methionine or homocysteine is only marginal, which means that the semi-essential amino acid cysteine can become an essential amino acid and must be supplied more through the diet. The homoserine resulting from cystathionine cleavage is converted by deamination to alpha-ketobutyrate, which is degraded to propionyl-CoA and, as a result of decarboxylation and a subsequent vitamin B12-dependent rearrangement of the carboxyl group, to succinyl-CoA. The latter is a metabolite of the citrate cycle in which, among other things, energy is obtained in the form of GTP (guanosine triphosphate) and the reduction equivalents NADH and FADH2, which lead to the production of energy in the form of ATP (adenosine triphosphate) in the subsequent respiratory chain. The process of transsulfation can only take place in certain tissues. These include liver, kidney, pancreas (pancreas) and brain. In the process of remethylation, homocysteine synthesis from methionine is reversed. Thus, homocysteine first reacts with adenosine to form S-adenosylhomocysteine (SAH) with cleavage of water. Subsequently, under the influence of the vitamin B12-dependent methionine synthase, methyl group transfer occurs with the formation of S-adenosylmethionine (SAM). The methyl group is supplied by 5-methyl-tetrahydrofolate (5-MTHF), which transfers the CH3 group to the coenzyme of methionine synthase, vitamin B12 (cobalamin). Loaded with methyl cobalamin, methionine synthase transports the CH3 group to SAH, synthesizing SAM. Finally, methionine can be released from S-adenosylmethionine. 5-MTHF is the methylated active form of folic acid (vitamin B9) and has the function of acceptor and transmitter of methyl groups in intermediary metabolism. The release of the CH3 group to the cobalamin of methionine synthase results in the active tetrahydrofolic acid, which is now available for new methyl group transfers.Vitamin B12 functions in a similar way. In the form of methyl cobalamin, it participates in enzymatic reactions and is responsible for the uptake and release of methyl groups. Finally, the methionine cycle is directly linked to folic acid and vitamin B12 metabolism In the liver and kidney, homocysteine can also be remethylated to methionine via betaine homocysteine methyltransferase (BHMT). The methyl group required for methionine synthesis is supplied by betaine, a quaternary ammonium compound with three methyl groups, and transferred to the methyltransferase. Betaine is thus both substrate and methyl group donor for BHMT. The methyltransferase now transports the CH3 residue onto homocysteine to form methionine and dimethylglycine. The pathway of remethylation of homocysteine or methionine synthesis via BHMT is independent of folic acid and vitamin B12. Consequently, the water-soluble B vitamins folic acid, B12, and B6 are involved in the overall metabolism of methionine and homocysteine. If there is a deficit of even just one of these vitamins, homocysteine degradation is inhibited. The result is a significantly increased homocysteine plasma level. This can therefore be used as a marker for the supply of folic acid, vitamin B6 and B12. Increased homocysteine levels in the blood can be normalized by increased administration of all three B vitamins in combination. Because the administration of folic acid alone can significantly lower plasma homocysteine levels, an adequate supply of folic acid appears to be particularly important.
Risk factor homocysteine
Deficiencies of vitamins B6, B9, and B12 result in the inability to remethylate homocysteine to methionine and consequently accumulate in both the extracellular and intracellular spaces. Homocysteine concentrations of 5-15 µmol/l are considered normal. Values above 15 µmol/l indicate hyperhomocysteinemia – elevated homocysteine levels. Several studies suggest that a plasma homocysteine level above 15 µmol/l is an independent risk factor for both dementia and cardiovascular disease, especially atherosclerosis (hardening of the arteries). The risk of coronary heart disease (CHD) seems to increase continuously with increasing homocysteine concentration in the blood. According to the latest calculations, 9.7% of deaths from heart disease in the USA are due to excessive homocysteine levels. Increased homocysteine concentrations in the blood can often be observed with increasing age due to insufficient intake of vitamins, including vitamins B6, B9 and B12. On average, men from the age of 50 and women from the age of 75 have a homocysteine plasma level that is above 15µmol/l. Accordingly, older people are at particularly high risk of cardio- and cerebrovascular disease. In order to reduce this risk, people of advanced age should give preference to plenty of fruit, vegetables and cereal products, but also to foods of animal origin, such as eggs, fish, and milk and dairy products, as these provide sufficient amounts of the B vitamins B6, B9 and B12 in particular. Homocysteine can lead to atherosclerotic changes in the vascular system through the formation of free radicals. However, homocysteine itself is also capable of intervening directly in the process of atherosclerosis. Under the influence of the transition metal ion copper or the copper-containing oxidase caeruloplasmin, homocysteine is oxidized to homocystine, producing hydrogen peroxide (H2O2). H2O2 is a reactive oxygen species (ROS) that reacts in the presence of iron (Fe2+) via the Fenton reaction to form a hydroxyl radical. Hydroxyl radicals are highly reactive molecules that can damage, among other things, the endothelium of blood vessels, proteins, fatty acids, and nucleic acids (DNA and RNA). Homocysteine can also take on radical character itself due to its terminal thiol group (SH group). For this purpose, the heavy metal iron in the form of Fe2+ withdraws an electron from the SH group of homocysteine. Homocysteine thus takes on a prooxidant effect and strives to snatch electrons from an atom or molecule, resulting in the formation of free radicals. These also take away electrons from other substances, and in this way a chain reaction leads to a constant increase in the number of radicals in the body (oxidative stress).Oxidative stress is often the cause of changes in gene expression characterized, for example, by increased secretion of cytokines and growth factors, respectively. Cytokines, such as interferons, interleukins and tumor necrosis factors, are secreted from erythrocytes (red blood cells) and leukocytes (white blood cells) as well as fibroblasts and promote the migration of smooth muscle cells in the walls of blood vessels from the tunica media – the muscle layer lying in the middle of blood vessels – to the tunica intima – connective tissue layer with endothelial cells that lines the inner blood vessel layer towards the blood side. Proliferation of smooth myocytes (muscle cells) then occurs in the tunica intima. The proliferation of myocytes is induced not only by the free radicals but also by homocysteine itself via the induction of cyclin D1 and cyclin A mRNA. Homocysteine is also able to induce the biosynthesis of collagen, which is a component of the extracellular matrix (extracellular matrix, intercellular substance, ECM, ECM), in cultured smooth muscle cells at the mRNA level. This results in increased production of the extracellular matrix. Oxidative stress damages cell walls and cell components and in this way can trigger apoptosis, programmed cell death. This particularly affects the endothelial cells of vascular walls. The renewal of vascular endothelial cells is inhibited by homocysteine, presumably via decreased carboxymethylation of p21ras, so that progression of cellular damage cannot be stopped. p21ras is a protein responsible for cell cycle control. The damaged vascular endothelium leads to increased adhesion (adherence) of neutrophils (white blood cells), such as monocytes, which are a component of the blood clotting system and specifically “stick” to the damaged endothelial cells to close wounds. The increased adhesion of neutrophils activates them to produce hydrogen peroxide, which further damages the endothelial cells. In addition, vascular wall damage results in the passage of monocytes and oxidized LDL from the bloodstream into the tunica intima, where monocytes differentiate into macrophages and take up the oxidized LDL without limit. Pathophysiologically relevant concentrations of homocysteine-50 to 400 µmol/l-enhance the adhesion of neutrophils to the endothelium and their subsequent migration across the endothelium (diapedesis). In the tunica intima, macrophages develop into lipid-rich foam cells that rapidly burst and die as a result of lipid overload. The numerous lipid fractions released in the process, as well as the cellular debris from the macrophages, are now deposited in the intima. Both the proliferating muscle cells and the foam cells and deposits in the form of lipids, lymphocytes, proteoglycans, collagen and elastin lead to thickening of the intima or inner blood vessel layer. In the further course, the typical atherosclerotic vascular changes are formed – formation of fatty streaks, necrosis (cell death), sclerosis (hardening of the connective tissue) and calcification (storage of calcium). These phenomena in the vascular system are also known as fibrous plaques. During the progression of atherosclerosis, the plaques may rupture, causing the intima to tear. Increased platelets (blood clots) accumulate on the damaged vascular endothelium to close the wound, inducing the formation of thrombi (blood clots). Thrombi can completely occlude the blood vessel, significantly impairing blood flow. As the tunica intima thickens due to growth of atherosclerotic plaques, the lumen of the blood vessels becomes increasingly narrow. The development of thrombi further contributes to stenosis (narrowing). The stenoses lead to circulatory disorders and play a major role in the pathogenesis of cardiovascular diseases. The tissues and organs supplied by a diseased artery suffer from oxygen deficiency due to impaired blood flow. When the carotid artery (large arteries of the neck) is affected, the brain is undersupplied with oxygen, increasing the risk of apoplexy (stroke). If the coronary arteries are affected by stenosis, the heart cannot be supplied with sufficient oxygen and myocardial infarction (heart attack) may result.In many cases, fibrous plaques develop in the arteries of the legs, which is not infrequently associated with arterial occlusive disease (pAVD), also known as shop window disease, leading to pain in the calf, thigh, or buttock muscles after prolonged walking. Numerous studies have found that patients with cardiovascular disease and cerebral palsy, especially those with atherosclerosis, stroke, Alzheimer’s disease, Parkinson’s disease, and senile dementia, have elevated plasma homocysteine levels. This finding confirms that homocysteine is a major risk factor for atherosclerosis and its sequelae. In addition to elevated plasma homocysteine levels, obesity, physical inactivity, hypertension (high blood pressure), hypercholesterolemia, increased alcohol and coffee consumption, and smoking are also independent risk factors for cardio- and cerebrovascular disease. Other functions of methionine.
- Lipotrophy – methionine exhibits lipotrophic properties, which means it has a fat-solubilizing effect and thus helps prevent excessive fat storage in the liver; in studies, methionine deficiency caused fatty liver in rats, but this could be reversed by methionine supplementation – methionine supports regeneration of liver and kidney tissue; methionine also finds use in hypertriglyceridemia, as it promotes the breakdown of triglycerides
- Utilization of important nutrients and vital substances – since methionine is needed for the metabolism of some amino acids, such as glycine and serine, the need for methionine increases in a high-protein diet; sufficiently high methionine plasma levels are also important to ensure optimal utilization of the trace element selenium in the body.
- Antioxidant – as a radical scavenger methionine makes free radicals harmless
- Detoxification – in connection with the trace element zinc methionine increases the excretion of heavy metals and can thus prevent, for example, lead poisoning
- Regeneration of the body after training phases – in anabolic phases, for example after training, the methionine requirement is particularly high due to the necessary regeneration or recovery of the stressed body.
- Lowering the histamine plasma level – via methylation of histamine, methionine acts as a natural antihistamine – it thus keeps the histamine level in the blood low and is therefore beneficial in atopy – hypersensitivity reactions – or allergies; Histamine is released in IgE-mediated allergic reactions of the “immediate type” – TypeI – or by complement factors from the mast cells or basophilic granulocytes and is thus involved in the defense of exogenous substances; in addition, histamine in the central nervous system regulates the sleep-wake rhythm and appetite control.
- Urinary tract infections – methionine can be used in urinary tract infections to prevent recurrent infections; the essential amino acid shifts the pH of urine into the acidic range, which prevents the settlement of pathogenic germs and bacteria and the formation of phosphate stones in the kidney
- Improve memory performance in AIDS patients – methionine is able to inhibit the progression of HIV-related encephalopathy; adequate dietary methionine intake – up to 6 g daily – protects patients from AIDS-related damage to the nervous system, such as progressive dementia, and can thus improve memory performance.
Biological valence
The biological value (BW) of a protein is a measure of how efficiently a dietary protein can be converted into endogenous protein or used for endogenous protein biosynthesis. It is a question of whether the content of essential amino acids in the dietary protein is optimally matched to the spectrum of protein building blocks in the body. The higher the quality of a dietary protein, the less of it needs to be ingested to maintain protein biosynthesis and meet the body’s requirements – provided the body is adequately supplied with energy in the form of carbohydrates and fats, so that dietary proteins are not used for energy production. Of particular interest are the essential amino acids, which are important for endogenous protein biosynthesis. All of these must be present simultaneously for protein formation at the site of synthesis in the cell.An intracellular deficit of only one amino acid would bring the synthesis of the protein in question to a standstill, which would mean that the sub-molecules already built up would have to be degraded again. The essential amino acid that is the first to limit endogenous protein biosynthesis due to its insufficient concentration in dietary protein is called the first-limiting amino acid. Methionine is the first-limiting amino acid in legumes such as beans and lupins, in yeast, and in the milk protein casein. In linseed, meat, and gelatin, methionine is the second-limiting amino acid due to its low content. In these foods, methionine is thus the second limiting amino acid. Biological value is the most common method for determining protein quality. To determine it, the two nutrition researchers Kofranyi and Jekat developed a special method in 1964. According to this method, for each test protein, the amount sufficient to maintain the nitrogen balance is determined – determination of the N-balance minimum. The reference value is whole egg protein, the biological value of which is arbitrarily set at 100 or 1-100%. It has the highest BW among all individual proteins. If a protein is utilized by the body less efficiently than egg protein, the BW of this protein is below 100. Proteins from animal foods have a higher BW than proteins from plant sources due to their high content of proteins (egg white), which are usually rich in essential amino acids. Plant foods have rather low amounts of protein in relation to weight. Consequently, animal protein generally meets human needs better. To give an example, pork has a BW of 85, while rice has a BW of only 66. By cleverly combining different protein carriers, foods with a low biological value can be upgraded by mutually balancing the limiting amino acids. This is known as the complementary effect of different proteins. In most cases, the combination of vegetable and animal protein results in an enhancement. Thus, the low BW of rice is significantly upgraded by eating it together with fish. Fish contains abundant essential amino acids, such as methionine, and is therefore of high biological value. But even a combination of purely vegetable protein sources, such as the joint intake of corn and beans, achieves a biological value of almost 100. With the help of the supplementation effect of individual proteins, it is possible to achieve a BW that is higher than that of whole egg protein. The greatest value-added effect is achieved by the combination of 36% whole egg with 64% potato protein, which reaches a BW of 136.
Methionine degradation
Methionine and other amino acids can in principle be metabolized and degraded in all cells and organs of the organism. However, the enzyme systems for catabolism of the essential amino acids are found predominantly in hepatocytes (liver cells). When methionine is broken down, ammonia (NH3) and an alpha-keto acid are released. On the one hand, alpha-keto acids can be used directly for energy production. On the other hand, since methionine is glucogenic in nature, they serve as a precursor for gluconeogenesis (new formation of glucose) in the liver and muscles. For this purpose, methionine is degraded via several intermediate steps to homoserine to pyruvate and succinyl-CoA. Both pyruvate and succinyl-CoA, which is an intermediate of the citrate cycle, can serve as substrates for gluconeogenesis. Glucose represents an important energy source for the body. The erythrocytes (red blood cells) and the renal medulla are totally dependent on glucose for energy. The brain only partially, because in starvation metabolism it can obtain up to 80% of its energy from ketone bodies. When glucose is broken down, ATP (adenosine triphosphate) is formed, the cell’s most important energy source. When its phosphate bonds are hydrolytically cleaved by enzymes, ADP (adenosine diphosphate) or AMP (adenosine monophosphate) is formed. The energy released in this process enables the body’s cells to perform osmotic (transport processes through membranes), chemical (enzymatic reactions) or mechanical work (muscle contractions). Ammonia enables the synthesis of non-essential amino acids, purines, porphyrins, plasma proteins and proteins of infection defense. Since NH3 in free form is neurotoxic even in very small amounts, it must be fixed and excreted.Ammonia can cause serious cell damage by inhibiting energy metabolism and pH shifts. Ammonia fixation occurs through a glutamate dehydrogenase reaction. In this process, ammonia released into extrahepatic tissues is transferred to alpha-ketoglutarate, resulting in glutamate. The transfer of a second amino group to glutamate results in the formation of glutamine. The process of glutamine synthesis serves as a preliminary ammonia detoxification. Glutamine, which is mainly formed in the brain, transports the bound and thus harmless NH3 to the liver. Other forms of transport of ammonia to the liver are aspartic acid (aspartate) and alanine. The latter amino acid is formed by binding of ammonia to pyruvate in the muscles. In the liver, ammonia is released from glutamine, glutamate, alanine and aspartate. NH3 is now introduced into the hepatocytes (liver cells) for final detoxification using carbamyl-phosphate synthetase in urea biosynthesis. Two ammonia molecules form a molecule of urea, which is non-toxic and excreted through the kidneys in the urine. Via the formation of urea, 1-2 moles of ammonia can be eliminated daily. The extent of urea synthesis is subject to the influence of diet, especially protein intake in terms of quantity and biological quality. In an average diet, the amount of urea in daily urine is in the range of about 30 grams.
Persons with impaired kidney function are unable to excrete excess urea via the kidneys. Affected individuals should eat a low-protein diet to avoid increased production and accumulation of urea in the kidney due to amino acid breakdown.
