Glycine

Glycine[1]
Names
IUPAC name
Glycine
Other names
Aminoethanoic acid
Aminoacetic acid
Glycocoll
Identifiers
3D model (JSmol)
Abbreviations Gly, G
ChEBI
ChemSpider
DrugBank
ECHA InfoCard 100.000.248
EC Number 200-272-2
KEGG
UNII
Properties
C2H5NO2
Molar mass 75.07 g/mol
Appearance white solid
Density 1.607 g/cm3
Melting point 233 °C (451 °F; 506 K) (decomposition)
24.99 g/100 mL (25 °C)[2]
Solubility soluble in pyridine
sparingly soluble in ethanol
insoluble in ether
Acidity (pKa) 2.34 (carboxyl), 9.6 (amino)[3]
-40.3·10−6 cm3/mol
Pharmacology
B05CX03 (WHO)
Hazards
Safety data sheet See: data page
Lethal dose or concentration (LD, LC):
2600 mg/kg (mouse, oral)
Supplementary data page
Refractive index (n),
Dielectric constant (εr), etc.
Thermodynamic
data
 Phase behaviour
solid–liquid–gas
UV, IR, NMR, MS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
YesY verify (what is YesYN ?)
Infobox references

Glycine (abbreviated as Gly or G) is the amino acid that has a single hydrogen atom as its side chain. It is the simplest possible amino acid. The chemical formula of glycine is NH2‐CH2‐COOH. Glycine is one of the proteinogenic amino acids. Its codons are GGU, GGC, GGA, GGG of the genetic code.

Glycine is a colorless, sweet-tasting crystalline solid. It is unique among the proteinogenic amino acids in that it is achiral. It can fit into hydrophilic or hydrophobic environments since it exists as zwitterion at natural pH, due to its minimal side chain of only one hydrogen atom. The acyl radical is glycyl.

Glycine is a white crystalline solid

History and etymology

Glycine was first isolated from gelatin in 1820.[4] The name comes from the ancient Greek word γλυκύς "sweet tasting"[5] (which is also related to the prefixes glyco- and gluco-, as in glycoprotein and glucose).

Production

Glycine was discovered in 1820, by Henri Braconnot who boiled a gelatinous object with sulfuric acid.[6]

Glycine is manufactured industrially by treating chloroacetic acid with ammonia:[7]

ClCH2COOH + 2 NH3 → H2NCH2COOH + NH4Cl

About 15 million kg are produced annually in this way.[8]

In the United States and Japan, glycine is produced via the Strecker amino acid synthesis.[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.[9][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.

Glycine is also cogenerated as an impurity in the synthesis of EDTA, arising from reactions of the ammonia coproduct.[11]

Acid-base properties and structures

In aqueous solution, glycine itself is amphoteric: at low pH the molecule can be protonated with a pKa of about 2.4 and at high pH it loses a proton with a pKa of about 9.6 (precise values of pKa depend on temperature and ionic strength). The nature of glycine in aqueous solution has been investigated by theoretical methods.[12] 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 = [NH3+CH2CO−
2]/[H2NCH2CO2H]

Both isomers of glycine have been observed by microwave spectroscopy in the gas phase.[13] The solid-state structure has been analyzed in detail.[14]


Metabolism

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, but the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis.[15] In most organisms, the enzyme serine hydroxymethyltransferase catalyses this transformation via the cofactor pyridoxal phosphate:[16]

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:[16]

CO2 + NH+
4 + 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.[16][17]

Degradation

Glycine is degraded via three pathways. The predominant pathway in animals and plants involves the glycine cleavage enzyme:[16]

Glycine + tetrahydrofolate + NAD+ → CO2 + NH+
4 + 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.[16]

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.[16]

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. [18]

Physiological function

The principal function of glycine is as a precursor to proteins, such as its periodically repeated role in the formation of the collagen helix in conjunction with hydroxyproline. It is also a building block for numerous natural products.

As a biosynthetic intermediate

In higher eukaryotes, δ-aminolevulinic acid, the key precursor to porphyrins, is biosynthesized from glycine and succinyl-CoA by the enzyme ALA synthase. Glycine provides the central C2N subunit of all purines.[16]

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 receptors. In contrast to the inhibitory role of glycine in the spinal cord, this behaviour is facilitated at the (NMDA) glutamatergic receptors which are excitatory.[19] The LD50 of glycine is 7930 mg/kg in rats (oral),[20] and it usually causes death by hyperexcitability.

A 2014 review on sleep aids noted that glycine can improve sleep quality, citing a study in which 3 grams of glycine before bedtime improved sleep quality in humans.[21][22] Glycine has also been positively tested as an add-on treatment for schizophrenia.[23]

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.

Animal and human foods

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.[25] Certain drug formulations include glycine to improve gastric absorption of the drug.[25]

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, and metal complexing agents.[26]

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.

Laboratory research

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-labeling 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

In 2009, glycine sampled in 2004 from comet Wild 2 by the NASA spacecraft Stardust was confirmed – the first discovery of glycine outside the Earth, although glycine had been identified in the Murchison meteorite in 1970.[27] The discovery of cometary glycine bolstered the theory of panspermia, which claims that the "building-blocks" of life are widespread throughout the Universe.[28] In 2016, detection of glycine within Comet 67P/Churyumov-Gerasimenko by the Rosetta spacecraft was announced.[29]

The detection of glycine outside the solar system in the interstellar medium has been debated.[30] In 2008, the Max Planck Institute for Radio Astronomy discovered the glycine-like molecule aminoacetonitrile in the Large Molecule Heimat, a giant gas cloud near the galactic center in the constellation Sagittarius.[31]

See also

References

  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. ↑ "glycine". Encyclopædia Britannica Online. Retrieved 2015-12-06.
  5. ↑ "glycine". Oxford Dictionaries. Retrieved 2015-12-06.
  6. ↑ R.H.A. Plimmer (1912) [1908]. R.H.A. Plimmer; F.G. Hopkins, eds. 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.
  7. ↑ Ingersoll, A. W.; Babcock, S. H. (1932). "Hippuric acid". Org. Synth. 12: 40.; Coll. Vol., 2, p. 328
  8. ↑ Drauz, Karlheinz; Grayson, Ian; Kleemann, Axel; Krimmer, Hans-Peter; Leuchtenberger, Wolfgang and Weckbecker, Christoph (2007) "Amino Acids" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim. doi:10.1002/14356007.a02_057.pub2
  9. 1 2 "Glycine Conference (prelim)". USITC. Retrieved 2014-06-13.
  10. ↑ U.S. International Trade Commission, "Glycine From China." Investigation No. 731-TA-718 (Second Review), Publication No. 3810, October 2005
  11. ↑ Hart, J. Roger (2005) "Ethylenediaminetetraacetic Acid and Related Chelating Agents" in Ullmann's Encyclopedia of Industrial Chemistry, Wiley-VCH, Weinheim. doi:10.1002/14356007.a10_095
  12. ↑ 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. Am. Chem. Soc. 106 (7): 1945–1950. doi:10.1021/ja00319a008.
  13. ↑ Suenram, R.D.; Lovas, F.J (1980). "Millimeter wave spectrum of glycine. A new conformer". J. Am. Chem. Soc. 102 (24): 7180–7184. doi:10.1021/ja00544a002.
  14. ↑ 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.
  15. ↑ Meléndez-Hevia, E; De Paz-Lugo, P; Cornish-Bowden, A; Cárdenas, M. L. (December 2009). "A weak link in metabolism: the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis". Journal of biosciences. 34 (6): 853–72. PMID 20093739. doi:10.1007/s12038-009-0100-9.
  16. 1 2 3 4 5 6 7 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
  17. ↑ 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.
  18. ↑ Hahn RG (1993). "Dose-dependent half-life of glycine". Urological Research. 21 (4): 289–291. PMID 8212419. doi:10.1007/BF00307714.
  19. ↑ "Recent development in NMDA receptors". Chinese Medical Journal. 2000.
  20. ↑ "Safety (MSDS) data for glycine". The Physical and Theoretical Chemistry Laboratory Oxford University. 2005. Retrieved 2006-11-01.
  21. ↑ Halson SL (2014). "Sleep in elite athletes and nutritional interventions to enhance sleep". Sports Med. 44 Suppl 1: S13–23. PMC 4008810 Freely accessible. PMID 24791913. doi:10.1007/s40279-014-0147-0. Glycine (a non-essential amino acid) functions as an inhibitory neurotransmitter in the central nervous system and also acts as a co-agonist of glutamate receptors. In a Japanese study [73], glycine has been shown to improve subjective sleep. Yamadera et al. [74] also reported shorter sleep-onset latencies measured by polysomnography. The authors suggested that potential mechanisms involve increased vasodilation and thus lowering of core temperature and increased extracellular 5-HT release in the prefrontal cortex of rats [74]
  22. ↑ 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.
  23. ↑ 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 (1): 32–8. PMID 15205876. doi:10.1007/s00213-003-1709-2.
  24. ↑ "Glycine From Japan and Korea" (PDF). U.S. International Trade Commission. January 2008. Retrieved 2014-06-13.
  25. 1 2
  26. ↑ "Notice of Preliminary Determination of Sales at Less Than Fair Value: Glycine From India" Federal Register 72 (7 November 2007): 62827.
  27. ↑ Kvenvolden, Keith A.; Lawless, James; Pering, Katherine; Peterson, Etta; Flores, Jose; Ponnamperuma, Cyril; Kaplan, Isaac R.; Moore, Carleton (1970). "Evidence for extraterrestrial amino-acids and hydrocarbons in the Murchison meteorite". Nature. 228 (5275): 923–926. Bibcode:1970Natur.228..923K. PMID 5482102. doi:10.1038/228923a0.
  28. ↑ Reuters (18 August 2009). "Building block of life found on comet - Thomson Reuters 2009". Retrieved 2009-08-18.
  29. ↑ European Space Agency (27 May 2016). "Rosetta’s comet contains ingredients for life". Retrieved 2016-06-05.
  30. ↑ Snyder LE, Lovas FJ, Hollis JM, et al. (2005). "A rigorous attempt to verify interstellar glycine". Astrophys J. 619 (2): 914–930. Bibcode:2005ApJ...619..914S. arXiv:astro-ph/0410335 Freely accessible. doi:10.1086/426677.
  31. ↑ Staff. "Organic Molecule, Amino Acid-Like, Found In Constellation Sagittarius 27 March 2008 - Science Daily". Retrieved 2008-09-16.

Further reading

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