Examine individual changes

'{{for|the plant genus|glycine (plant)}}{{redirect|Gly|the unit of measurement|light-year}} {{chembox | Watchedfields = changed | verifiedrevid = 464190930 | Reference=<ref>{{Merck11th|4386}}.</ref> | ImageFileL1 = Glycine-zwitterion-2D-skeletal.png | ImageSizeL1 = 120px | ImageFileR1_Ref = {{chemboximage|correct|??}} | ImageFileR1 = Glycin - Glycine.svg | ImageSizeR1 = 73px | ImageFileL2 = Glycine-from-xtal-2008-3D-balls.png | ImageSizeL2 = 120px | ImageNameL2 = Zwitterion of glycine | ImageFileR2 = Glycine-3D-balls.png | ImageSizeR2 = 100px | IUPACName = Glycine | OtherNames = Aminoethanoic acid <br /> Aminoacetic acid | Section1 = {{Chembox Identifiers | Abbreviations = '''Gly''', '''G''' | UNII_Ref = {{fdacite|correct|FDA}} | UNII = TE7660XO1C | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 773 | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D00011 | InChI = 1/C2H5NO2/c3-1-2(4)5/h1,3H2,(H,4,5) | InChIKey = DHMQDGOQFOQNFH-UHFFFAOYAW | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C2H5NO2/c3-1-2(4)5/h1,3H2,(H,4,5) | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = DHMQDGOQFOQNFH-UHFFFAOYSA-N | CASNo = 56-40-6 | CASNo_Ref = {{cascite|correct|CAS}} | EC-number = 200-272-2 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 730 | PubChem = 750 | IUPHAR_ligand = 727 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB00145 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 15428 | SMILES = C(C(=O)O)N | ATCCode_prefix = B05 | ATCCode_suffix = CX03 }} | Section2 = {{Chembox Properties | C=2 | H=5 | N=1 | O=2 | MolarMass = 75.07 | Appearance = white solid | Density = 1.607 g/cm³ | MeltingPt = 233 °C (decomposition) | Solubility = 24.99 g/100 mL (25 °C)<ref>{{cite web|url=http://prowl.rockefeller.edu/aainfo/solub.htm |title=Solubilities and densities |publisher=Prowl.rockefeller.edu |date= |accessdate=2013-11-13}}</ref> | SolubleOther = soluble in [[pyridine]] <br> sparingly soluble in [[ethanol]] <br> insoluble in [[ether]] | pKa = 2.34 (carboxyl), 9.6 (amino)<ref>Dawson, R.M.C., et al., ''Data for Biochemical Research'', Oxford, Clarendon Press, 1959.</ref> }} | Section3 = {{Chembox Hazards | EUIndex = | FlashPt = | Autoignition = | LD50 = 2600 mg/kg (mouse, oral) }} }} '''Glycine''' (abbreviated as '''Gly''' or '''G''')<ref>{{IUPAC-IUB amino acids 1983}}.</ref> is an [[organic compound]] with the [[chemical formula|formula]] NH₂CH₂COOH. Having a [[hydrogen]] substituent as its [[Side chain|side-chain]], glycine is the smallest of the 20 [[amino acid]]s commonly found in [[protein]]s, and indeed is the smallest possible. Its [[codon]]s are GGU, GGC, GGA, GGG of the [[genetic code]]. Glycine is a colourless, sweet-tasting crystalline solid. It is unique among the [[proteinogenic amino acid]]s in that it is not [[chirality (chemistry)|chiral]]. It can fit into [[Hydrophile|hydrophilic]] or [[Hydrophobe|hydrophobic]] environments, due to its minimal side chain of only one hydrogen atom. ==Production== Glycine was discovered in 1820, by [[Henri Braconnot]] who boiled a [[gelatinous]] object with [[sulfuric acid]].<ref>{{cite book |author= R.H.A. Plimmer |editor= R.H.A. Plimmer & F.G. Hopkins |title= The chemical composition of the proteins |url= http://books.google.com/?id=7JM8AAAAIAAJ&pg=PA112 |accessdate= January 18, 2010 |edition= 2nd |series= Monographs on biochemistry |volume= Part I. Analysis |origyear= 1908 |year= 1912 |publisher= Longmans, Green and Co. |location= London|page= 82}}</ref> Glycine is manufactured industrially by treating [[chloroacetic acid]] with [[ammonia]]:<ref>{{OrgSynth | first1 = A. W. | last1 = Ingersoll | first2 = S. H. | last2 = Babcock | title = Hippuric acid | prep=cv2p0328 | volume = 12 | pages = 40 | year = 1932 | collvol = 2 | collvolpages = 328}}</ref> :ClCH₂COOH + 2 NH₃ → H₂NCH₂COOH + NH₄Cl About 15 million kg are produced annually in this way.<ref>Karlheinz Drauz, Ian Grayson, Axel Kleemann, Hans-Peter Krimmer, Wolfgang Leuchtenberger, Christoph Weckbecker “Amino Acids” in Ullmann's Encyclopedia of Industrial Chemistry 2007, Wiley-VCH, Weinheim. {{DOI|10.1002/14356007.a02_057.pub2}}</ref> In the USA (by GEO Specialty Chemicals, Inc.) and in Japan (by [http://showadenko.us/product/glycine.html?product_type=Amino%20Acetic%20Acid%20-%20Glycine Showa Denko KK]), glycine is produced via the [[Strecker amino acid synthesis]].<ref name="usitc.gov">{{cite web|url=http://www.usitc.gov/trade_remedy/731_ad_701_cvd/investigations/2007/glycine_from_india_japan_korea/preliminary/DOC/Glycine%20Conference%20(prelim).wpd |title=Glycine Conference (prelim) |publisher=USITC |date= |accessdate=2014-06-13}}</ref><ref>[http://www.geosc.com/consumeradditives/default.aspx ]{{dead link|date=November 2013}}</ref> There are two producers of glycine in the United States: Chattem Chemicals, Inc., a subsidiary of [[Mumbai, India | Mumbai]]-based [[Sun Pharmaceutical]], and GEO Specialty Chemicals, Inc., which purchased the glycine and [[Naphthalenesulfonate|naphthalene sulfonate]] production facilities of Hampshire Chemical Corp, a subsidiary of [[Dow Chemical]].<ref name="usitc.gov"/><ref>U.S. International Trade Commission, "Glycine From China." Investigation No. 731-TA-718 (Second Review), Publication No. 3810, October 2005</ref> Chattem's manufacturing process ("MCA" process) occurs in batches and results in a finished product with some residual chloride but no sulfate, while GEO’s manufacturing process is considered a semi-batch process and results in a finished product with some residual sulfate but no chloride. I REALLY HATE BIOLOGY! == Acid-base properties and structures == [[File:Glycine-protonation-states-2D-skeletal.png|600px]] In aqueous solution glycine itself is [[amphoteric]]: at low pH the molecule can be protonated with a pK_a of about 9.6 and at high pH it loses a proton with a pK_a of about 2.4 (precise values of pK_a depend on temperature and ionic strength). The nature of glycine in aqueous solution has been investigated by theoretical methods.<ref>{{cite journal |last1=Bonaccorsi |first1=R. |last2=Palla |first2=P. |last3=Tomasi |first3=J.|year=1984 |title=Conformational energy of glycine in aqueous solutions and relative stability of the zwitterionic and neutral forms. An ab initio study |journal=J. Amer. Chem. Soc |volume=106 |issue=7 |pages=1945–1950 |doi=10.1021/ja00319a008 }}</ref> In solution the ratio of concentrations of the two isomers is independent of both the analytical concentration and of pH. This ratio is simply the equilibrium constant for isomerization. :<math>K=\mathrm{ \frac {[H_3N^+CH_2CO_2^-]} {[H_2NCH_2CO_2H]}}</math> Both isomers of glycine have been observed by microwave spectroscopy in the gas phase.<ref>{{cite journal |last1=Suenram |first1=R.D. |last2=Lovas |first2=F.J |year=1980 |title=Millimeter wave spectrum of glycine. A new conformer|journal=J. Amer. Chem. Soc |volume=102 |issue=24 |pages=7180–7184 |doi=10.1021/ja00544a002}}</ref> The solid-state structure has been analyzed in detail.<ref>{{cite journal |last1=Jönsson |first1=P.-G. |last2=Kvick |first2=Å |year=1972 |title=Precision neutron diffraction structure determination of protein and nucleic acid components. III. The crystal and molecular structure of the amino acid -glycine |journal=Precision neutron diffraction structure determination of protein and nucleic acid components. III. The crystal and molecular structure of the amino acid -glycine |volume=B28 |issue=6 |pages=1827-1833 |doi=10.1107/S0567740872005096}}</ref> <!-- Glycine exists in [[Zwitterion|zwitterionic]] form in solution. In this form, the partial charges on different atoms as determined using Gasteiger charge method are given as follows: N (+0.2358), H (attached to N) (+0.1964), alpha-C (+0.001853), H (attached to alpha-C) (+0.08799), carbonyl C (+0.085) and carbonyl O (-0.5445). --> <!-- Removed as unsourced --> ==Biosynthesis== Glycine is not essential to the human diet, as it is biosynthesized in the body from the amino acid [[serine]], which is in turn derived from [[3-phosphoglycerate]]. In most organisms, the enzyme [[Serine hydroxymethyltransferase]] catalyses this transformation via the cofactor [[pyridoxal phosphate]]:<ref name="Lehninger"/> : serine + [[tetrahydrofolate]] → glycine + ''N⁵'',''N¹⁰''-Methylene tetrahydrofolate + H₂O In the liver of [[vertebrate]]s, glycine synthesis is catalyzed by [[glycine synthase]] (also called glycine cleavage enzyme). This conversion is readily reversible:<ref name="Lehninger"/> : CO₂ + NH₄⁺ + ''N⁵'',''N¹⁰''-Methylene tetrahydrofolate + NADH + H⁺ → Glycine + tetrahydrofolate + NAD⁺ Glycine is coded by [[codons]] GGU, GGC, GGA and GGG. Most proteins incorporate only small quantities of glycine. A notable exception is [[collagen]], which contains about 35% glycine.<ref name="Lehninger">{{Lehninger4th|pages=127, 675–77, 844, 854}}</ref><ref name="SzpakJAS">{{Cite journal |last=Szpak |first=Paul |title=Fish bone chemistry and ultrastructure: implications for taphonomy and stable isotope analysis | url=http://uwo.academia.edu/PaulSzpak/Papers/827788/Fish_Bone_Chemistry_and_Ultrastructure_Implications_for_Taphonomy_and_Stable_Isotope_Analysis |journal=[[Journal of Archaeological Science (journal)|Journal of Archaeological Science]] |year=2011 |volume=38 |issue=12 |pages=3358–3372 |doi=10.1016/j.jas.2011.07.022 }}</ref> ==Degradation== Glycine is degraded via three pathways. The predominant pathway in animals and plants involves the [[glycine cleavage enzyme]]<ref name="Lehninger"/> : Glycine + tetrahydrofolate + NAD⁺ → CO₂ + NH₄⁺ + ''N⁵'',''N¹⁰''-Methylene tetrahydrofolate + [[NADH]] + H⁺ In the second pathway, glycine is degraded in two steps. The first step is the reverse of glycine biosynthesis from serine with serine hydroxymethyl transferase. Serine is then converted to [[pyruvate]] by [[serine dehydratase]].<ref name="Lehninger"/> In the third pathway of glycine degradation, glycine is converted to [[glyoxylate]] by [[D-amino acid oxidase]]. Glyoxylate is then oxidized by hepatic [[lactate dehydrogenase]] to [[oxalate]] in an NAD⁺-dependent reaction.<ref name="Lehninger"/> The half-life of glycine and its elimination from the body varies significantly based on dose. In one study, the half-life was between 0.5 and 4.0 hours. <ref>{{cite journal | author = Hahn RG | year = 1993 | title = Dose-dependent half-life of glycine | journal = Urological Research | volume = 21 | issue = 4 | pages = 289–291 | doi = 10.1007/BF00307714 | pmid = 8212419 }}</ref> ==Physiological function== The principal function of glycine is as a precursor to proteins, such as its periodically repeated role in the formation of [[Collagen]] helix in conjunction with [[Hydroxyproline]]. It is also a building block to numerous natural products. ===As a biosynthetic intermediate=== In higher [[eukaryotes]], [[D-Aminolevulinic acid]], the key precursor to [[porphyrins]], is biosynthesized from glycine and [[succinyl-CoA]]. Glycine provides the central C₂N subunit of all [[purine]]s.<ref name="Lehninger"/> ===As a neurotransmitter=== Glycine is an inhibitory [[neurotransmitter]] in the [[central nervous system]], especially in the [[spinal cord]], brainstem, and retina. When [[glycine receptors]] are activated, [[chloride]] enters the neuron via ionotropic receptors, causing an [[Inhibitory postsynaptic potential]] (IPSP). [[Strychnine]] is a strong antagonist at ionotropic glycine receptors, whereas [[bicuculline]] is a weak one. Glycine is a required [[co-agonist]] along with [[glutamate]] for [[NMDA receptor]]s. In contrast to the inhibitory role of glycine in the spinal cord, this behaviour is facilitated at the ([[NMDA]]) glutaminergic receptors which are excitatory.<ref> {{cite web |url=http://www.cmj.org/Periodical/paperlist.asp?id=LW7347&linkintype=pubmed |title=Recent development in NMDA receptors |year=2000 |publisher=Chinese Medical Journal}}</ref> The {{LD50}} of glycine is 7930&nbsp;mg/kg in rats (oral),<ref>{{cite web |url=http://physchem.ox.ac.uk/MSDS/GL/glycine.html |title=Safety (MSDS) data for glycine |year=2005 |publisher= The Physical and Theoretical Chemistry Laboratory Oxford University |accessdate=2006-11-01}}</ref> and it usually causes death by hyperexcitability. There is some evidence showing that 3000 milligrams of glycine before bedtime improves sleep quality.<ref>{{Cite journal|author=Yamadera W, Inagawa K, Chiba S, Bannai M, Takahashi M, Nakayama K |title=Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes |journal=Sleep and Biological rhythms |volume=5 |issue=2 |pages=126–131 |year=2007 |doi=10.1111/j.1479-8425.2007.00262.x}}</ref>{{Primary source-inline|date=December 2012}} Glycine has also been positively tested as an add-on treatment for schizophrenia. <ref>{{Cite journal|author=Coyle JT, G Tsai |title=The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia |journal=Psychopharmacology |volume=174 |pages=32-28 |year=2004 |doi=10.1007/s00213-003-1709-2}}</ref> ==Uses== In the US, glycine is typically sold in two grades: [[United States Pharmacopeia]] (“USP”), and technical grade. Most glycine is manufactured as USP grade material for diverse uses. USP grade sales account for approximately 80 to 85 percent of the U.S. market for glycine. * Pharmaceutical grade glycine is produced for some pharmaceutical applications, such as intravenous injections, where the customer’s purity requirements often exceed the minimum required under the USP grade designation. Pharmaceutical grade glycine is often produced to proprietary specifications and is typically sold at a premium over USP grade glycine. * Technical grade glycine, which may or may not meet USP grade standards, is sold for use in industrial applications; e.g., as an agent in metal complexing and finishing. Technical grade glycine is typically sold at a discount to USP grade glycine.<ref>{{cite web|url=http://www.usitc.gov/publications/701_731/pub3980.pdf |title=Glycine From Japan and Korea |format=PDF |date= |accessdate=2014-06-13}}</ref> ===Animal and human foods=== Other markets for USP grade glycine include its use an additive in [[pet food]] and [[compound feed|animal feed]]. For humans, glycine is sold as a sweetener/taste enhancer. Certain food supplements and protein drinks contain glycine.<ref name="geosc1">[http://www.geosc.com/constructionandindustrial/Miscellaneous/GEO%20Glycine%20Brochure.pdf ]{{dead link|date=November 2013}}</ref> Certain drug formulations include glycine to improve gastric absorption of the drug.<ref name="geosc1"/> ===Cosmetics and miscellaneous applications=== Glycine serves as a [[buffering agent]] in [[antacids]], [[analgesics]], [[antiperspirants]], cosmetics, and toiletries. Many miscellaneous products use glycine or its derivatives, such as the production of rubber sponge products, fertilizers, metal complexants.<ref name=72FR62827>"Notice of Preliminary Determination of Sales at Less Than Fair Value: Glycine From India" Federal Register 72 (7 November 2007): 62827.</ref> ===Chemical feedstock=== Glycine is an intermediate in the synthesis of a variety of chemical products. It is used in the manufacture of the herbicide [[glyphosate]]. Glyphosate is a non-selective systemic herbicide used to kill weeds, especially perennials, and used in cut-stump treatment as a forestry herbicide. ===Research and Development=== Glycine is a significant component of some solutions used in the [[Polyacrylamide gel electrophoresis|SDS-PAGE]] method of protein analysis. It serves as a buffering agent, maintaining pH and preventing sample damage during electrophoresis. Glycine is also used to remove protein-labelling antibodies from [[Western Blot]] membranes to enable the probing of numerous proteins of interest from SDS-PAGE gel. This allows more data to be drawn from the same specimen, increasing the reliability of the data, reducing the amount of sample processing, and number of samples required. This process is known as 'stripping'. ==Presence in space== The detection of glycine in the [[interstellar medium]] has been debated.<ref name=Snyder>{{cite journal |author=Snyder LE, Lovas FJ, Hollis JM, et al. |title=A rigorous attempt to verify interstellar glycine |journal=Astrophys J |volume=619 |issue=2 |pages=914–930 |year=2005 |doi=10.1086/426677 |bibcode=2005ApJ...619..914S | arxiv = astro-ph/0410335}}</ref> In 2008, the glycine-like molecule [[aminoacetonitrile]] was discovered in the [[Large Molecule Heimat]], a giant gas cloud near the galactic center in the constellation [[Sagittarius (constellation)|Sagittarius]] by the [[Max Planck Institute for Radio Astronomy]].<ref>{{cite web |url=http://www.sciencedaily.com/releases/2008/03/080326161658.htm |author=Staff|title=Organic Molecule, Amino Acid-Like, Found In Constellation Sagittarius 27 March 2008 - Science Daily |accessdate=2008-09-16}}</ref> In 2009, glycine sampled in 2004 from comet [[Wild 2]] by the [[NASA]] spacecraft [[Stardust (spacecraft)|Stardust]] was confirmed, the first discovery of extraterrestrial glycine. That mission's results bolstered the theory of [[panspermia]], which claims that the "seeds" of life are widespread throughout the universe.<ref>{{cite news |url=http://www.reuters.com/article/scienceNews/idUSTRE57H02I20090818 |author=Reuters|title=Building block of life found on comet - Thomson Reuters 2009 |accessdate=2009-08-18 | date=18 August 2009}}</ref> == See also == * [[Trimethylglycine]] * [[Amino acid neurotransmitter]] == References == {{Reflist|2}} ==Further reading== On attempts to detect glycine in interstellar medium *{{cite journal |author=Kuan YJ, Charnley SB, Huang HC, et al. |title=Interstellar glycine |journal=Astrophys J |volume=593 |issue=2 |pages=848–867 |year=2003 |doi=10.1086/375637 |bibcode=2003ApJ...593..848K}} *{{cite web |url=http://www.newscientist.com/news/news.jsp?id=ns99992558 |author=Rachel Nowak |title=Amino acid found in deep space - 18 July 2002 - New Scientist |accessdate=2007-07-01}} ==External links== {{commonscat}} * [http://gmd.mpimp-golm.mpg.de/Spectrums/8a79d6c1-4849-4634-afe1-112d6e346bfb.aspx Glycine MS Spectrum] * [http://www.pdrhealth.com/drugs/altmed/altmed-mono.aspx?contentFileName=ame0084.xml&contentName=Glycine&contentId=247 Glycine] at PDRHealth.com * [http://www.chem.qmul.ac.uk/iubmb/enzyme/reaction/AminoAcid/GlyCleave.html Glycine cleavage system] * [http://www.schizophrenia.com/glycinetreat.htm Glycine Therapy - A New Direction for Schizophrenia Treatment?] * {{cite journal | title = Organic Molecule, Amino Acid-Like, Found In Constellation Sagittarius | journal = ScienceDaily |date=27 March 2008| url = http://www.sciencedaily.com/releases/2008/03/080326161658.htm}} * {{cite journal | journal = Psychiatric Times | volume = 25 | issue = 14 | title = A New Class of Antipsychotic Drugs: Enhancing Neurotransmission Mediated by NMDA Receptors | author = Guochuan E. Tsai |date=1 December 2008| url = http://www.psychiatrictimes.com/display/article/10168/1357569}} * [http://chemsub.online.fr/name/glycine.html ChemSub Online (Glycine)]. * [http://www.jpl.nasa.gov/news/news.cfm?release=2009-126 NASA scientists have discovered glycine, a fundamental building block of life, in samples of comet Wild 2 returned by NASA's Stardust spacecraft.] {{Amino acids}} {{Amino acid metabolism intermediates}} {{Neurotransmitters}} {{Glycinergics}} {{Glutamatergics}} {{Molecules detected in outer space}} [[Category:Flavour enhancers]] [[Category:Glucogenic amino acids]] [[Category:Neurotransmitters]] [[Category:Proteinogenic amino acids]]'