AMMONIA

Relevant Data

Flavouring Substances Approved by European Union:

  • Ammonia [show]

General Information

MaintermAMMONIA
CAS Reg.No.(or other ID)7664-41-7
Regnum 176.170
176.210

From www.fda.gov

Computed Descriptors

Download SDF
2D Structure
CID222
IUPAC Nameazane
InChIInChI=1S/H3N/h1H3
InChI KeyQGZKDVFQNNGYKY-UHFFFAOYSA-N
Canonical SMILESN
Molecular FormulaNH3
Wikipediaammonia

From Pubchem

Computed Properties

Property Name Property Value
Molecular Weight17.031
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count1
Rotatable Bond Count0
Complexity0.0
CACTVS Substructure Key Fingerprint A A A D c Q A C A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A Q A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A A = =
Topological Polar Surface Area1.0
Monoisotopic Mass17.027
Exact Mass17.027
XLogP3None
XLogP3-AA-0.7
Compound Is CanonicalizedTrue
Formal Charge0
Heavy Atom Count1
Defined Atom Stereocenter Count0
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Isotope Atom Count0
Covalently-Bonded Unit Count1

From Pubchem

Food Additives Biosynthesis/Degradation

ADMET Predicted Profile --- Classification

Model Result Probability
Absorption
Blood-Brain BarrierBBB+0.9661
Human Intestinal AbsorptionHIA+0.9835
Caco-2 PermeabilityCaco2+0.7599
P-glycoprotein SubstrateNon-substrate0.8904
P-glycoprotein InhibitorNon-inhibitor0.9847
Non-inhibitor0.9874
Renal Organic Cation TransporterNon-inhibitor0.9068
Distribution
Subcellular localizationLysosome0.7461
Metabolism
CYP450 2C9 SubstrateNon-substrate0.8500
CYP450 2D6 SubstrateNon-substrate0.8103
CYP450 3A4 SubstrateNon-substrate0.8303
CYP450 1A2 InhibitorNon-inhibitor0.9108
CYP450 2C9 InhibitorNon-inhibitor0.9240
CYP450 2D6 InhibitorNon-inhibitor0.9357
CYP450 2C19 InhibitorNon-inhibitor0.9450
CYP450 3A4 InhibitorNon-inhibitor0.9707
CYP Inhibitory PromiscuityLow CYP Inhibitory Promiscuity0.8311
Excretion
Toxicity
Human Ether-a-go-go-Related Gene InhibitionWeak inhibitor0.9391
Non-inhibitor0.9755
AMES ToxicityNon AMES toxic0.9837
CarcinogensCarcinogens 0.6116
Fish ToxicityLow FHMT0.5819
Tetrahymena Pyriformis ToxicityLow TPT0.8472
Honey Bee ToxicityHigh HBT0.7691
BiodegradationReady biodegradable0.9292
Acute Oral ToxicityIII0.5994
Carcinogenicity (Three-class)Non-required0.5999

From admetSAR

ADMET Predicted Profile --- Regression

Model Value Unit
Absorption
Aqueous solubility0.3591LogS
Caco-2 Permeability1.5723LogPapp, cm/s
Distribution
Metabolism
Excretion
Toxicity
Rat Acute Toxicity2.0168LD50, mol/kg
Fish Toxicity2.1885pLC50, mg/L
Tetrahymena Pyriformis Toxicity-0.9037pIGC50, ug/L

From admetSAR

Toxicity Profile

Route of ExposureOral ; inhalation ; dermal
Mechanism of ToxicityThe 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 . 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.
MetabolismAmmonia 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.
Toxicity ValuesLD50: 350 mg/kg (Oral, Rat) LC50: 3360 mg/m3 over 1 hour (Inhalation, Mouse) Severe hyperammonemia is characterized by serum ammonia levels greater than 1000 μmol/L
Lethal Dose2500 to 4500 ppm over 30 minutes for an adult human.
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Minimum Risk LevelAcute Inhalation: 1.7 ppm Chronic Inhalation: 0.1 ppm
Health EffectsAcute 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.
TreatmentAcute 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.
Reference
  1. Lemberg A, Fernandez MA: Hepatic encephalopathy, ammonia, glutamate, glutamine and oxidative stress. Ann Hepatol. 2009 Apr-Jun;8(2):95-102.[19502650 ]
  2. Azzi A, Boscoboinik D, Clement S, Marilley D, Ozer NK, Ricciarelli R, Tasinato A: Alpha-tocopherol as a modulator of smooth muscle cell proliferation. Prostaglandins Leukot Essent Fatty Acids. 1997 Oct;57(4-5):507-14.[9430404 ]
  3. Remer T: Influence of nutrition on acid-base balance--metabolic aspects. Eur J Nutr. 2001 Oct;40(5):214-20.[11842946 ]
  4. Pita AM, Wakabayashi Y, Fernandez-Bustos MA, Virgili N, Riudor E, Soler J, Farriol M: Plasma urea-cycle-related amino acids, ammonium levels, and urinary orotic acid excretion in short-bowel patients managed with an oral diet. Clin Nutr. 2003 Feb;22(1):93-8.[12553956 ]
  5. Zupke C, Sinskey AJ, Stephanopoulos G: Intracellular flux analysis applied to the effect of dissolved oxygen on hybridomas. Appl Microbiol Biotechnol. 1995 Dec;44(1-2):27-36.[8579834 ]
  6. Albrecht J, Norenberg MD: Glutamine: a Trojan horse in ammonia neurotoxicity. Hepatology. 2006 Oct;44(4):788-94.[17006913 ]
  7. Shawcross DL, Olde Damink SW, Butterworth RF, Jalan R: Ammonia and hepatic encephalopathy: the more things change, the more they remain the same. Metab Brain Dis. 2005 Sep;20(3):169-79.[16167195 ]
  8. Norenberg MD, Rama Rao KV, Jayakumar AR: Ammonia neurotoxicity and the mitochondrial permeability transition. J Bioenerg Biomembr. 2004 Aug;36(4):303-7.[15377862 ]
  9. Brautbar N, Wu MP, Richter ED: Chronic ammonia inhalation and interstitial pulmonary fibrosis: a case report and review of the literature. Arch Environ Health. 2003 Sep;58(9):592-6.[15369278 ]
  10. Seiler N: Ammonia and Alzheimer's disease. Neurochem Int. 2002 Aug-Sep;41(2-3):189-207.[12020619 ]
  11. Yoshida Y, Higashi T, Nouso K, Nakatsukasa H, Nakamura SI, Watanabe A, Tsuji T: Effects of zinc deficiency/zinc supplementation on ammonia metabolism in patients with decompensated liver cirrhosis. Acta Med Okayama. 2001 Dec;55(6):349-55.[11779097 ]
  12. Huizenga JR, Teelken AW, Tangerman A, de Jager AE, Gips CH, Jansen PL: Determination of ammonia in cerebrospinal fluid using the indophenol direct method. Mol Chem Neuropathol. 1998 Jun-Aug;34(2-3):169-77.[10327416 ]
  13. Cohen BI: The significance of ammonia/gamma-aminobutyric acid (GABA) ratio for normality and liver disorders. Med Hypotheses. 2002 Dec;59(6):757-8.[12445521 ]
  14. Kochar DK, Agarwal P, Kochar SK, Jain R, Rawat N, Pokharna RK, Kachhawa S, Srivastava T: Hepatocyte dysfunction and hepatic encephalopathy in Plasmodium falciparum malaria. QJM. 2003 Jul;96(7):505-12.[12881593 ]
  15. Cooper AJ: Role of glutamine in cerebral nitrogen metabolism and ammonia neurotoxicity. Ment Retard Dev Disabil Res Rev. 2001;7(4):280-6.[11754523 ]
  16. Kaiho T, Tanaka T, Tsuchiya S, Yanagisawa S, Takeuchi O, Miura M, Saigusa N, Miyazaki M: Effect of the herbal medicine Dai-kenchu-to for serum ammonia in hepatectomized patients. Hepatogastroenterology. 2005 Jan-Feb;52(61):161-5.[15783019 ]
  17. Nybo L, Dalsgaard MK, Steensberg A, Moller K, Secher NH: Cerebral ammonia uptake and accumulation during prolonged exercise in humans. J Physiol. 2005 Feb 15;563(Pt 1):285-90. Epub 2004 Dec 20.[15611036 ]
  18. Huizenga JR, Vissink A, Kuipers EJ, Gips CH: Helicobacter pylori and ammonia concentrations of whole, parotid and submandibular/sublingual saliva. Clin Oral Investig. 1999 Jun;3(2):84-7.[10803116 ]
  19. Satoh M, Yokoya S, Hachiya Y, Hachiya M, Fujisawa T, Hoshino K, Saji T: Two hyperandrogenic adolescent girls with congenital portosystemic shunt. Eur J Pediatr. 2001 May;160(5):307-11.[11388600 ]
  20. Suarez I, Bodega G, Fernandez B: Glutamine synthetase in brain: effect of ammonia. Neurochem Int. 2002 Aug-Sep;41(2-3):123-42.[12020613 ]
  21. Helewski K, Kowalczyk-Ziomek G, Konecki J: [Ammonia and GABA-ergic neurotransmission in pathogenesis of hepatic encephalopathy]. Wiad Lek. 2003;56(11-12):560-3.[15058165 ]
  22. Grasten SM, Juntunen KS, Poutanen KS, Gylling HK, Miettinen TA, Mykkanen HM: Rye bread improves bowel function and decreases the concentrations of some compounds that are putative colon cancer risk markers in middle-aged women and men. J Nutr. 2000 Sep;130(9):2215-21.[10958815 ]
  23. Geier M, Bosch OJ, Boeckh J: Ammonia as an attractive component of host odour for the yellow fever mosquito, Aedes aegypti. Chem Senses. 1999 Dec;24(6):647-53.[10587497 ]
  24. Iwata H, Ueda Y: Pharmacokinetic considerations in development of a bioartificial liver. Clin Pharmacokinet. 2004;43(4):211-25.[15005636 ]
  25. Ohmoto K, Miyake I, Tsuduki M, Ohno S, Yamamoto S: Control of solitary gastric fundal varices and portosystemic encephalopathy accompanying liver cirrhosis by balloon-occluded retrograde transvenous obliteration (B-RTO): a case report. Hepatogastroenterology. 1999 Mar-Apr;46(26):1249-52.[10370701 ]
  26. Verrotti A, Greco R, Morgese G, Chiarelli F: Carnitine deficiency and hyperammonemia in children receiving valproic acid with and without other anticonvulsant drugs. Int J Clin Lab Res. 1999;29(1):36-40.[10356662 ]
  27. Hussein HS, Flickinger EA, Fahey GC Jr: Petfood applications of inulin and oligofructose. J Nutr. 1999 Jul;129(7 Suppl):1454S-6S.[10395620 ]

From T3DB

Taxonomic Classification

KingdomInorganic compounds
SuperclassHomogeneous non-metal compounds
ClassHomogeneous other non-metal compounds
SubclassNot available
Intermediate Tree NodesNot available
Direct ParentHomogeneous other non-metal compounds
Alternative Parents
Molecular FrameworkNot available
SubstituentsHomogeneous other non metal
DescriptionThis compound belongs to the class of inorganic compounds known as homogeneous other non-metal compounds. These are inorganic non-metallic compounds in which the largest atom belongs to the class of 'other non-metals'.

From ClassyFire

Targets

Target Details

Complement C3

General Function:
Receptor binding
Specific Function:
C3 plays a central role in the activation of the complement system. Its processing by C3 convertase is the central reaction in both classical and alternative complement pathways. After activation C3b can bind covalently, via its reactive thioester, to cell surface carbohydrates or immune aggregates.Derived from proteolytic degradation of complement C3, C3a anaphylatoxin is a mediator of local inflammatory process. In chronic inflammation, acts as a chemoattractant for neutrophils (By similarity). It induces the contraction of smooth muscle, increases vascular permeability and causes histamine release from mast cells and basophilic leukocytes.C3-beta-c: Acts as a chemoattractant for neutrophils in chronic inflammation.Acylation stimulating protein: adipogenic hormone that stimulates triglyceride (TG) synthesis and glucose transport in adipocytes, regulating fat storage and playing a role in postprandial TG clearance. Appears to stimulate TG synthesis via activation of the PLC, MAPK and AKT signaling pathways. Ligand for C5AR2. Promotes the phosphorylation, ARRB2-mediated internalization and recycling of C5AR2 (PubMed:8376604, PubMed:2909530, PubMed:9059512, PubMed:10432298, PubMed:15833747, PubMed:16333141, PubMed:19615750).
Gene Name:
C3
Uniprot ID:
P01024
Molecular Weight:
187146.73 Da
References
  1. ATSDR - Agency for Toxic Substances and Disease Registry (2004). Toxicological profile for ammonia. U.S. Public Health Service in collaboration with U.S. Environmental Protection Agency (EPA). : http://www.atsdr.cdc.gov/toxprofiles/tp126.html
Target Details

Transient receptor potential cation channel subfamily A member 1

General Function:
Temperature-gated cation channel activity
Specific Function:
Receptor-activated non-selective cation channel involved in detection of pain and possibly also in cold perception and inner ear function (PubMed:25389312, PubMed:25855297). Has a central role in the pain response to endogenous inflammatory mediators and to a diverse array of volatile irritants, such as mustard oil, cinnamaldehyde, garlic and acrolein, an irritant from tears gas and vehicule exhaust fumes (PubMed:25389312, PubMed:20547126). Is also activated by menthol (in vitro)(PubMed:25389312). Acts also as a ionotropic cannabinoid receptor by being activated by delta(9)-tetrahydrocannabinol (THC), the psychoactive component of marijuana (PubMed:25389312). May be a component for the mechanosensitive transduction channel of hair cells in inner ear, thereby participating in the perception of sounds. Probably operated by a phosphatidylinositol second messenger system (By similarity).
Gene Name:
TRPA1
Uniprot ID:
O75762
Molecular Weight:
127499.88 Da
References
  1. Nilius B, Prenen J, Owsianik G: Irritating channels: the case of TRPA1. J Physiol. 2011 Apr 1;589(Pt 7):1543-9. doi: 10.1113/jphysiol.2010.200717. Epub 2010 Nov 15. [21078588 ]

From T3DB