Glycine

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Glycine[1]
Glycine-zwitterion-2D-skeletal.png Glycin - Glycine.svg
Zwitterion of glycine Glycine-3D-balls.png
Identifiers
Abbreviations Gly, G
CAS number 56-40-6 YesY
PubChem 750
ChemSpider 730 YesY
UNII TE7660XO1C YesY
EC-number 200-272-2
DrugBank DB00145
KEGG D00011 YesY
ChEBI CHEBI:15428 YesY
ChEMBL CHEMBL773 YesY
IUPHAR ligand 727
ATC code B05CX03
Jmol-3D images Image 1
Properties
Molecular formula C2H5NO2
Molar mass 75.07 g mol−1
Appearance white solid
Density 1.607 g/cm3
Melting point 233 °C (decomposition)
Solubility in water 24.99 g/100 mL (25 °C)[2]
Solubility soluble in ethanol, pyridine
insoluble in ether
Acidity (pKa) 2.34 (carboxyl), 9.6 (amino)[3]
Hazards
MSDS External MSDS
LD50 2600 mg/kg (mouse, oral)
Supplementary data page
Structure and
properties
n, εr, etc.
Thermodynamic
data
Phase behaviour
Solid, liquid, gas
Spectral data UV, IR, NMR, MS
Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa)
 YesY (verify) (what is: YesY/N?)
Infobox references

Glycine (abbreviated as Gly or G)[4] is an organic compound with the formula NH2CH2COOH. Having a hydrogen substituent as its side-chain, glycine is the smallest of the 20 amino acids commonly found in proteins. Its codons are GGU, GGC, GGA, GGG of the genetic code.

Glycine is a colourless, sweet-tasting crystalline solid. It is unique among the proteinogenic amino acids in that it is not chiral. It can fit into hydrophilic or hydrophobic environments, due to its minimal side chain of only one hydrogen atom.

Production[edit]

Glycine was discovered in 1820, by Henri Braconnot who boiled a gelatinous object with sulfuric acid.[5]

Glycine is manufactured industrially by treating chloroacetic acid with ammonia:[6]

ClCH2COOH + 2 NH3 → H2NCH2COOH + NH4Cl

About 15 million kg are produced annually in this way.[7]

In the USA (by GEO Specialty Chemicals, Inc.) and in Japan (by Showa Denko, K.K.)Showa Denko America, glycine is produced via the Strecker amino acid synthesis.[8][9]

There are two producers of glycine in the United States: Chattem Chemicals, Inc., a subsidiary of Mumbai-based Sun Pharmaceutical, and GEO Specialty Chemicals, Inc., which purchased the glycine and naphthalene sulfonate production facilities of Hampshire Chemical Corp, a subsidiary of Dow Chemical.[8][10]

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.

Acid-base properties and structures[edit]

Glycine-protonation-states-2D-skeletal.png

In aqueous solution glycine itself is amphoteric: at low pH the molecule can be protonated with a pKa of about 9.6 and at high pH it loses a proton with a pKa of about 2.4 (precise values of pKa depend on temperature and ionic strength). The nature of glycine in aqueous solution has been investigated by theoretical methods.[11] 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.

K=\mathrm{ \frac {[H_3N^+CH_2CO_2^-]} {[H_2NCH_2CO_2H]}}

Both isomers of glycine have been observed by microwave spectroscopy in the gas phase.[12] The solid-state structure has been analyzed in detail.[13]

Biosynthesis[edit]

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:[14]

serine + tetrahydrofolate → glycine + N5,N10-Methylene tetrahydrofolate + H2O

In the liver of vertebrates, glycine synthesis is catalyzed by glycine synthase (also called glycine cleavage enzyme). This conversion is readily reversible:[14]

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.[14][15]

Degradation[edit]

Glycine is degraded via three pathways. The predominant pathway in animals and plants involves the glycine cleavage enzyme[14]

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.[14]

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.[14]

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. [16]

Physiological function[edit]

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[edit]

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 purines.[14]

As a neurotransmitter[edit]

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 receptors. In contrast to the inhibitory role of glycine in the spinal cord, this behaviour is facilitated at the (NMDA) glutaminergic receptors which are excitatory.[17] The LD50 of glycine is 7930 mg/kg in rats (oral),[18] and it usually causes death by hyperexcitability.

There is some evidence showing that 3000 milligrams of glycine before bedtime improves sleep quality.[19][non-primary source needed] Glycine has also been positively tested as an add-on treatment for schizophrenia. [20]

Uses[edit]

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.[21]

Animal and human foods[edit]

Other markets for USP grade glycine include its use an additive in pet food and animal feed. For humans, glycine is sold as a sweetener/taste enhancer. Certain food supplements and protein drinks contain glycine.[22] Certain drug formulations include glycine to improve gastric absorption of the drug.[22]

Cosmetics and miscellaneous applications[edit]

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.[23]

Chemical feedstock[edit]

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 broadcast or used in the cut-stump treatment as a forestry herbicide.

Research and Development[edit]

Glycine is a significant component of some solutions used in the 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[edit]

The detection of glycine in the interstellar medium has been debated.[24] 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 by the Max Planck Institute for Radio Astronomy.[25] In 2009, glycine sampled in 2004 from comet Wild 2 by the NASA 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.[26]

See also[edit]

References[edit]

  1. ^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals (11th ed.), Merck, 1989, ISBN 091191028X , 4386.
  2. ^ "Solubilities and densities". Prowl.rockefeller.edu. Retrieved 2013-11-13. 
  3. ^ Dawson, R.M.C., et al., Data for Biochemical Research, Oxford, Clarendon Press, 1959.
  4. ^ "Nomenclature and symbolism for amino acids and peptides (IUPAC-IUB Recommendations 1983)", Pure Appl. Chem. 56 (5), 1984: 595–624, doi:10.1351/pac198456050595 .
  5. ^ R.H.A. Plimmer (1912) [1908]. R.H.A. Plimmer & F.G. Hopkins, ed. The chemical composition of the proteins. Monographs on biochemistry. Part I. Analysis (2nd ed.). London: Longmans, Green and Co. p. 82. Retrieved January 18, 2010. 
  6. ^ Ingersoll, A. W.; Babcock, S. H. (1932), "Hippuric acid", Org. Synth. 12: 40 ; Coll. Vol. 2: 328 
  7. ^ 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
  8. ^ a b http://www.usitc.gov/trade_remedy/731_ad_701_cvd/investigations/2007/glycine_from_india_japan_korea/preliminary/DOC/Glycine%20Conference%20(prelim).wpd
  9. ^ [1][dead link]
  10. ^ U.S. International Trade Commission, "Glycine From China." Investigation No. 731-TA-718 (Second Review), Publication No. 3810, October 2005
  11. ^ Bonaccorsi, R.; Palla, P.; Tomasi, J. (1984). "Conformational energy of glycine in aqueous solutions and relative stability of the zwitterionic and neutral forms. An ab initio study". J. Amer. Chem. Soc 106 (7): 1945–1950. doi:10.1021/ja00319a008. 
  12. ^ Suenram, R.D.; Lovas, F.J (1980). "Millimeter wave spectrum of glycine. A new conformer". J. Amer. Chem. Soc 102 (24): 7180–7184. doi:10.1021/ja00544a002. 
  13. ^ Jönsson, P.-G.; Kvick, Å (1972). "Precision neutron diffraction structure determination of protein and nucleic acid components. III. The crystal and molecular structure of the amino acid -glycine". Precision neutron diffraction structure determination of protein and nucleic acid components. III. The crystal and molecular structure of the amino acid -glycine B28 (6): 1827–1833. doi:10.1107/S0567740872005096. 
  14. ^ a b c d e f g Nelson, David L.; Cox, Michael M. (2005), Principles of Biochemistry (4th ed.), New York: W. H. Freeman, pp. 127, 675–77, 844, 854, ISBN 0-7167-4339-6 
  15. ^ Szpak, Paul (2011). "Fish bone chemistry and ultrastructure: implications for taphonomy and stable isotope analysis". Journal of Archaeological Science 38 (12): 3358–3372. doi:10.1016/j.jas.2011.07.022. 
  16. ^ Hahn RG (1993). "Dose-dependent half-life of glycine". Urological Research 21 (4): 289–291. doi:10.1007/BF00307714. PMID 8212419. 
  17. ^ "Recent development in NMDA receptors". Chinese Medical Journal. 2000. 
  18. ^ "Safety (MSDS) data for glycine". The Physical and Theoretical Chemistry Laboratory Oxford University. 2005. Retrieved 2006-11-01. 
  19. ^ Yamadera W, Inagawa K, Chiba S, Bannai M, Takahashi M, Nakayama K (2007). "Glycine ingestion improves subjective sleep quality in human volunteers, correlating with polysomnographic changes". Sleep and Biological rhythms 5 (2): 126–131. doi:10.1111/j.1479-8425.2007.00262.x. 
  20. ^ Coyle JT, G Tsai (2004). "The NMDA receptor glycine modulatory site: a therapeutic target for improving cognition and reducing negative symptoms in schizophrenia". Psychopharmacology 174: 32–28. doi:10.1007/s00213-003-1709-2. 
  21. ^ http://www.usitc.gov/publications/701_731/pub3980.pdf
  22. ^ a b [2][dead link]
  23. ^ "Notice of Preliminary Determination of Sales at Less Than Fair Value: Glycine From India" Federal Register 72 (7 November 2007): 62827.
  24. ^ Snyder LE, Lovas FJ, Hollis JM, et al. (2005). "A rigorous attempt to verify interstellar glycine". Astrophys J 619 (2): 914–930. arXiv:astro-ph/0410335. Bibcode:2005ApJ...619..914S. doi:10.1086/426677. 
  25. ^ Staff. "Organic Molecule, Amino Acid-Like, Found In Constellation Sagittarius 27 March 2008 - Science Daily". Retrieved 2008-09-16. 
  26. ^ Reuters (18 August 2009). "Building block of life found on comet - Thomson Reuters 2009". Retrieved 2009-08-18. 

Further reading[edit]

On attempts to detect glycine in interstellar medium

External links[edit]