Glycine

For the plant, see Glycine (plant).

Glycine[1]
IUPAC name Glycine
Other names Aminoethanoic acid Aminoacetic acid
Identifiers
Abbreviations	Gly, G
CAS number	56-40-6 Y
PubChem	750
ChemSpider	730 Y
UNII	TE7660XO1C Y
EC-number	200-272-2
DrugBank	DB00145
KEGG	D00011 Y
ChEBI	CHEBI:15428 Y
ChEMBL	CHEMBL773 Y
IUPHAR ligand	727
Jmol-3D images	Image 1
SMILES C(C(=O)O)N
InChI InChI=1S/C2H5NO2/c3-1-2(4)5/h1,3H2,(H,4,5) Y Key: DHMQDGOQFOQNFH-UHFFFAOYSA-N Y InChI=1/C2H5NO2/c3-1-2(4)5/h1,3H2,(H,4,5) Key: DHMQDGOQFOQNFH-UHFFFAOYAW
Properties
Molecular formula	C2H5NO2
Molar mass	75.07 g mol−1
Appearance	white solid
Density	1.1607 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
Y (verify) (what is: Y/N?) Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
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 cf. 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 two hydrogen atom side chain.

Production and key properties

Glycine was discovered in 1820, by Henri Braconnot who boiled gelatin 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 Shoadenko), glycine is produced via the Strecker amino acid synthesis.^[8]

There are two producers of glycine in the United States. Chattem Chemicals, Inc., purchased by Sun Pharmaceutical, who is an international pharmaceutical company based in Mumbai, India and GEO Specialty Chemicals, Inc., who purchased the glycine and naphthalene sulfonate production facilities of Dow/Hampshire Chemical Corp.^[8][9]

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.

Its pK_A values are 2.35 and 9.78, so above pH 9.78, most of the glycine exists as the anionic amine, H₂NCH₂CO₂^-. Below pH 2.35, its solutions contain mostly the cationic carboxylic acid H₃N⁺CH₂CO₂H. Its isoelectric point (pI) is 6.06.

Glycine exists in 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).

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:^[10]

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:^[10]

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.^[10][11]

Degradation

Glycine is degraded via three pathways. The predominant pathway in animals involves the catalysis of glycine cleavage enzyme, the same enzyme also involved in the biosynthesis of glycine. The degradation pathway is the reverse of this synthetic pathway:^[10]

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.^[10]

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.^[10]

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. ^[12]

Physiological function

The principal function of glycine is as a precursor to proteins. 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 purines.^[10]

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) glutaminergic receptors which are excitatory.^{[citation needed]} The LD₅₀ of glycine is 7930 mg/kg in rats (oral),^[13] and it usually causes death by hyperexcitability.

There is some evidence showing that 3000 milligrams of glycine before bedtime improves sleep quality.^[14]

Commercial 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.^[15]

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. Food supplements and protein drinks contain glycine. Certain drug formulations include glycine to improve gastric absorption of the drug.

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.^[16]

Zwitterionic salt (right) of glycine at neutral pH

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 broadcast or used in the cut-stump treatment as a forestry herbicide. Initially, glyphosate was sold only by Monsanto under the tradename Roundup, but is no longer under patent.

Presence in space

The detection of glycine in the interstellar medium has been debated.^[17] 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.^[18] 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.^[19]

See also

• Trimethylglycine

References

1. ^ The Merck Index: An Encyclopedia of Chemicals, Drugs, and Biologicals (11th ed.), Merck, 1989, ISBN 091191028X , 4386.
2. ^ http://prowl.rockefeller.edu/aainfo/solub.htm
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): 595–624, 1984, 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. http://books.google.com/?id=7JM8AAAAIAAJ&pg=PA112. Retrieved January 18, 2010. 
6. ^ Ingersoll, A. W.; Babcock, S. H. (1932), "Hippuric acid", Org. Synth. 12: 40, http://www.orgsyn.org/orgsyn/orgsyn/prepContent.asp?prep=cv2p0328 ; 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. ^ U.S. International Trade Commission, "Glycine From China." Investigation No. 731-TA-718 (Second Review), Publication No. 3810, October 2005
10. ^ ^{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 .
11. ^ 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. http://uwo.academia.edu/PaulSzpak/Papers/827788/Fish_Bone_Chemistry_and_Ultrastructure_Implications_for_Taphonomy_and_Stable_Isotope_Analysis. 
12. ^ Hahn RG (1993). "Dose-dependent half-life of glycine". Urological Research 21 (4): 289–291. doi:10.1007/BF00307714. PMID 8212419. 
13. ^ "Safety (MSDS) data for glycine". The Physical and Theoretical Chemistry Laboratory Oxford University. 2005. http://physchem.ox.ac.uk/MSDS/GL/glycine.html. Retrieved 2006-11-01. 
14. ^ 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. 
15. ^ http://hotdocs.usitc.gov/docs/pubs/701_731/pub3921.pdf
16. ^ "Notice of Preliminary Determination of Sales at Less Than Fair Value: Glycine From India" Federal Register 72 (7 November 2007): 62827.
17. ^ 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. 
18. ^ Staff. "Organic Molecule, Amino Acid-Like, Found In Constellation Sagittarius 27 March 2008 - Science Daily". http://www.sciencedaily.com/releases/2008/03/080326161658.htm. Retrieved 2008-09-16. 
19. ^ Reuters (18 August 2009). "Building block of life found on comet - Thomson Reuters 2009". http://www.reuters.com/article/scienceNews/idUSTRE57H02I20090818. Retrieved 2009-08-18. 

Further reading

On attempts to detect glycine in interstellar medium

• Kuan YJ, Charnley SB, Huang HC, et al. (2003). "Interstellar glycine". Astrophys J 593 (2): 848–867. Bibcode 2003ApJ...593..848K. doi:10.1086/375637. 
• Rachel Nowak. "Amino acid found in deep space - 18 July 2002 - New Scientist". http://www.newscientist.com/news/news.jsp?id=ns99992558. Retrieved 2007-07-01. 

External links

• Glycine at PDRHealth.com
• Glycine cleavage system
• Glycine Therapy - A New Direction for Schizophrenia Treatment?
• "Organic Molecule, Amino Acid-Like, Found In Constellation Sagittarius". ScienceDaily. 27 March 2008. http://www.sciencedaily.com/releases/2008/03/080326161658.htm. 
• Guochuan E. Tsai (1 December 2008). "A New Class of Antipsychotic Drugs: Enhancing Neurotransmission Mediated by NMDA Receptors". Psychiatric Times 25 (14). http://www.psychiatrictimes.com/display/article/10168/1357569. 
• ChemSub Online (Glycine).
• NASA scientists have discovered glycine, a fundamental building block of life, in samples of comet Wild 2 returned by NASA's Stardust spacecraft.