Ammonia
描述
Ammonia is a colourless alkaline gas and is one of the most abundant nitrogen-containing compounds in the atmosphere. It is an irritant with a characteristic pungent odor that is widely used in industry. Inasmuch as ammonia is highly soluble in water and, upon inhalation, is deposited in the upper airways, occupational exposures to ammonia have commonly been associated with sinusitis, upper airway irritation, and eye irritation. Acute exposures to high levels of ammonia have also been associated with diseases of the lower airways and interstitial lung. Small amounts of ammonia are naturally formed in nearly all tissues and organs of the vertebrate organism. Ammonia is both a neurotoxin and a metabotoxin. In fact, it is the most common endogenous neurotoxin. A neurotoxin is a compound that causes damage to neural tissue and neural cells. A metabotoxin is an endogenously produced metabolite that causes adverse health effects at chronically high levels. Ammonia is recognized to be central in the pathogenesis of a brain condition known as hepatic encephalopathy, which arises from various liver diseases and leads to a build up ammonia in the blood (hyperammonemia). More than 40% of people with cirrhosis develop hepatic encephalopathy. Part of the neurotoxicity of ammonia arises from the fact that it easily crosses the blood-brain barrier and is absorbed and metabolized by the astrocytes, a population of cells in the brain that constitutes 30% of the cerebral cortex. Astrocytes use ammonia when synthesizing glutamine from glutamate. The increased levels of glutamine lead to an increase in osmotic pressure in the astrocytes, which become swollen. There is increased activity of the inhibitory gamma-aminobutyric acid (GABA) system, and the energy supply to other brain cells is decreased. This can be thought of as an example of brain edema. The source of the ammonia leading to hepatic encephalopathy is not entirely clear. The gut produces ammonia, which is metabolized in the liver, and almost all organ systems are involved in ammonia metabolism. Colonic bacteria produce ammonia by splitting urea and other amino acids, however this does not fully explain hyperammonemia and hepatic encephalopathy. The alternative explanation is that hyperammonemia is the result of intestinal breakdown of amino acids, especially glutamine. The intestines have significant glutaminase activity, predominantly located in the enterocytes. On the other hand, intestinal tissues only have a little glutamine synthetase activity, making it a major glutamine-consuming organ. In addition to the intestine, the kidney is an important source of blood ammonia in patients with liver disease. Ammonia is also taken up by the muscle and brain in hepatic coma, and there is confirmation that ammonia is metabolized in muscle. Excessive formation of ammonia in the brains of Alzheimer's disease patients has also been demonstrated, and it has been shown that some Alzheimer's disease patients exhibit elevated blood ammonia concentrations. Ammonia is the most important natural modulator of lysosomal protein processing. Indeed, there is strong evidence for the involvement of aberrant lysosomal processing of beta-amyloid precursor protein (beta-APP) in the formation of amyloid deposits. Inflammatory processes and activation of microglia are widely believed to be implicated in the pathology of Alzheimer's disease. Ammonia is able to affect the characteristic functions of microglia, such as endocytosis, and cytokine production. Based on these facts, an ammonia-based hypothesis for Alzheimer's disease has been suggested (PMID: 17006913, 16167195, 15377862, 15369278). Chronically high levels of ammonia in the blood are associated with nearly twenty different inborn errors of metabolism including: 3-hydroxy-3-methylglutaryl-CoA lyase deficiency, 3-methyl-crotonylglycinuria, argininemia, argininosuccinic aciduria, beta-ketothiolase deficiency, biotinidase deficiency, carbamoyl phosphate synthetase deficiency, carnitine-acylcarnitine translocase deficiency, citrullinemia type I, hyperinsulinism-hyperammonemia syndrome, hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, isovaleric aciduria, lysinuric protein intolerance, malonic aciduria, methylmalonic aciduria, methylmalonic aciduria due to cobalamin-related disorders, propionic acidemia, pyruvate carboxylase deficiency, and short chain acyl CoA dehydrogenase deficiency (SCAD deficiency). Many of these inborn errors of metabolism are associated with urea cycle disorders or impairment to amino acid metabolism. High levels of ammonia in the blood (hyperammonemia) lead to the activation of NMDA receptors in the brain. This results in the depletion of brain ATP, which in turn leads to release of glutamate. Ammonia also leads to the impairment of mitochondrial function and calcium homeostasis, thereby decreasing ATP synthesis. Excess ammonia also increases the formation of nitric oxide (NO), which in turn reduces the activity of glutamine synthetase, and thereby decreases the elimination of ammonia in the brain (PMID: 12020609). As a neurotoxin, ammonia predominantly affects astrocytes. Disturbed mitochondrial function and oxidative stress, factors implicated in the induction of the mitochondrial permeability transition, appear to be involved in the mechanism of ammonia neurotoxicity. Ammonia can also affect the glutamatergic and GABAergic neuronal systems, the two prevailing neuronal systems of the cortical structures. All of these effects can lead to irreversible brain damage, coma, and/or death. Infants with urea cycle disorders and hyperammonemia initially exhibit vomiting and increasing lethargy. If untreated, seizures, hypotonia (poor muscle tone, floppiness), respiratory distress (respiratory alkalosis), and coma can occur. Adults with urea cycle disorders and hyperammonemia will exhibit episodes of disorientation, confusion, slurred speech, unusual and extreme combativeness or agitation, stroke-like symptoms, lethargy, and delirium. Ammonia also has toxic effects when an individual is exposed to ammonia solutions. Acute exposure to high levels of ammonia in air may be irritating to skin, eyes, throat, and lungs and cause coughing and burns. Lung damage and death may occur after exposure to very high concentrations of ammonia. Swallowing concentrated solutions of ammonia can cause burns in the mouth, throat, and stomach. Splashing ammonia into eyes can cause burns and even blindness.
类别
"Household Toxin", "Industrial/Workplace Toxin", "Food Toxin", "Natural Toxin"
同义词
"Ammonia anhydrous", "Ammonia water", "Anhydrous ammonia", "Azane", "Liquid ammonia", "NH(3)", "NH3", "Spirit of hartshorn"
InChI 标识符
InChI=1S/H3N/h1H3
键
InChIKey=QGZKDVFQNNGYKY-UHFFFAOYSA-N
化合物类型
Inorganic compounds
大分类
Homogeneous non-metal compounds
类型
Homogeneous other non-metal compounds
直接大类
Homogeneous other non-metal compounds
取代基
"Homogeneous other non metal"
外部描述符
"a small molecule", "azane", "mononuclear parent hydride"
地位
Detected and Not Quantified
蜂窝位置
"Cytoplasm", "Extracellular"
途径
"Amino Sugar Metabolism", "Ammonia Recycling", "Arginine and Proline Metabolism", "D-Arginine and D-Ornithine Metabolism", "Folate Metabolism", "Glucose-Alanine Cycle", "Glutamate Metabolism", "Glycine and Serine Metabolism", "Homocysteine Degradation", "Phenylalanine and Tyrosine Metabolism", "Threonine and 2-Oxobutanoate Degradation", "Urea Cycle", "3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency", "Argininemia", "Argininosuccinic Aciduria", "Beta-Ketothiolase Deficiency", "Biotinidase Deficiency", "Carbamoyl Phosphate Synthetase Deficiency", "Carnitine-acylcarnitine translocase deficiency", "Citrullinemia Type I", "Hyperinsulinism-Hyperammonemia Syndrome", "Hyperornithinemia-hyperammonemia-homocitrullinuria [HHH-syndrome]", "Isovaleric Aciduria", "Lysinuric Protein Intolerance", "Malonic Aciduria", "Methylmalonic Aciduria", "Methylmalonic Aciduria Due to Cobalamin-Related Disorders", "Propionic Acidemia", "Pyruvate Carboxylase Deficiency", "Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency)"
熔点/沸点/溶解度
-77.7°C//482 mg/mL at 24°C [DEAN,JA (1985)]
暴露途径
Oral (L958) ; inhalation (L958) ; dermal (L958)
毒性机制
The topical damage caused by ammonia is probably due mainly to its alkaline properties. Its high water solubility allows it to dissolve in moisture on the mucous membranes, skin, and eyes, forming ammonium hydroxide. Ammonium hydroxide causes saponification of cell membrane lipids, resulting in cell disruption and death. Additionally, it extracts water from the cells and initiates an inflammatory response, which further damages the surrounding tissues. Excess circulating levels of ammonia (hyperammonemia) can cause serious neurological effects. This is thought to involve the alteration of glutamate metabolism in the brain and resultant increased activation of NMDA receptors, which causes decreased protein kinase C-mediated phosphorylation of Na+/K+ ATPase, increased activity of Na+/K+ ATPase, and depletion of ATP. Ammonia can chemically interact with an internal thiolester bond of
complement 3 (C3). This causes a conformation change in C3, which activates the alternative complement pathway, causing the release of chemoattractants and the assembly of the membrane attack complex of complement. The altered C3 can also bind directly to phagocyte complement receptors, which causes the release of toxic oxygen species. (L958)
代谢
Ammonia can be absorbed by inhalation and oral routes exposure, and also to a much lesser extent through the skin and eyes. Most of the inhaled ammonia is retained in the upper respiratory tract and is subsequently eliminated in expired air, while ingested ammonia is readily absorbed in the intestinal tract. Ammonia that reaches the circulation is widely distributed to all body compartments although substantial first pass metabolism occurs in the liver where it is transformed into urea and glutamine. Ammonia or ammonium ion reaching the tissues is taken up by glutamic acid, which participates in transamination and other reactions. Ammonia is mainly excreted in the urine. (L958)
毒性值
LD50: 350 mg/kg (Oral, Rat) (A591)
LC50: 3360 mg/m3 over 1 hour (Inhalation, Mouse) (A591)
Severe hyperammonemia is characterized by serum ammonia levels greater than 1000 μmol/L
致死剂量
2500 to 4500 ppm over 30 minutes for an adult human. (L958)
致癌性
No indication of carcinogenicity to humans (not listed by IARC).
用途/来源
Ammonia is used directly on farm crops, and is also a precursor to foodstuffs and fertilizers. It is also found in many household and industrial cleaners. (L958)
最低风险等级
Acute Inhalation: 1.7 ppm (L134)
Chronic Inhalation: 0.1 ppm (L134)
健康影响
Acute exposure to high levels of ammonia in air may be irritating to skin, eyes, throat, and lungs and cause coughing and burns. Lung damage and death may occur after exposure to very high concentrations of ammonia. Swallowing concentrated solutions of ammonia can cause burns in mouth, throat, and stomach. Splashing ammonia into eyes can cause burns and even blindness. (L958)
Chronically high levels of ammonia in the blood are associated with nearly 20 different inborn errors of metabolism including: 3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency, Argininemia, Argininosuccinic Aciduria, Beta-Ketothiolase Deficiency, Biotinidase deficiency, Carbamoyl Phosphate Synthetase Deficiency, Carnitine-acylcarnitine translocase deficiency, Citrullinemia Type I, Hyperinsulinism-Hyperammonemia Syndrome, Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome, Isovaleric Aciduria, Lysinuric Protein Intolerance, Malonic Aciduria, Methylmalonic Aciduria, Methylmalonic Aciduria Due to Cobalamin-Related Disorders, Propionic acidemia, Pyruvate carboxylase deficiency and Short Chain Acyl CoA Dehydrogenase Deficiency (SCAD Deficiency). Hyperammonemia is one of the metabolic derangements that contribute to hepatic encephalopathy.
症状
Acute exposure leads to irritation and burning at the site of exposure. (L958)
Symptoms include cough, chest pain (severe), chest tightness, difficulty breathing and wheezing, tearing and burning of eyes, temporary blindness, throat pain (severe), mouth pain, lip swelling, heart and blood, rapid, weak pulse, collapse and shock.
Chronic exposure: Symptoms of hyperammonia include: lethargy, irritability, poor feeding, vomiting and seizures. Signs and symptoms of late-onset hyperammonemia (later in life) may include intermittent ataxia, intellectual impairment, failure to thrive, gait abnormality, behavior disturbances, epilepsy, recurrent Reye syndrome and protein avoidance.
治疗
Acute Exposure: EYES: irrigate opened eyes for several minutes under running water. INGESTION: do not induce vomiting. Rinse mouth with water (never give anything by mouth to an unconscious person). Seek immediate medical advice. SKIN: should be treated immediately by rinsing the affected parts in cold running water for at least 15 minutes, followed by thorough washing with soap and water. If necessary, the person should shower and change contaminated clothing and shoes, and then must seek medical attention. INHALATION: supply fresh air. If required provide artificial respiration.
Chronic Exposure: Intravenous arginine (argininosuccinase deficiency), sodium phenylbutyrate and sodium benzoate (ornithine transcarbamoylase deficiency) are pharmacologic agents commonly used as adjunctive therapy to treat hyperammonemia in patients.
维基百科链接
http://en.wikipedia.org/wiki/Ammonia
创建于
2009-03-06 18:58:11 UTC
更新于
2018-03-21 17:46:11 UTC