Glycine 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,
and indeed is the smallest possible. 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 Glycine was discovered in 1820, by Henri Braconnot
who boiled a gelatinous object with sulfuric acid.
Glycine is manufactured industrially by treating chloroacetic acid with ammonia:
ClCH2COOH + 2 NH3 → H2NCH2COOH + NH4Cl About 15 million kg are produced annually
in this way. In the USA and in Japan, glycine is produced
via the Strecker amino acid synthesis. 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.
Chattem's manufacturing 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
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. The nature
of glycine in aqueous solution has been investigated by theoretical methods. 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.
Both isomers of glycine have been observed by microwave spectroscopy in the gas phase.
The solid-state structure has been analyzed in detail.
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:
serine + tetrahydrofolate → glycine + N5,N10-Methylene tetrahydrofolate + H2O
In the liver of vertebrates, glycine synthesis is catalyzed by glycine synthase. This conversion
is readily reversible: 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.
Degradation Glycine is degraded via three pathways. The
predominant pathway in animals and plants involves the glycine cleavage enzyme
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.
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. 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. 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 purines. 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.
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 glutaminergic receptors which are excitatory. The LD50 of glycine is 7930 mg/kg in rats,
and it usually causes death by hyperexcitability. There is some evidence showing that 3000 milligrams
of glycine before bedtime improves sleep quality. Glycine has also been positively tested as
an add-on treatment for schizophrenia. Uses
In the US, glycine is typically sold in two grades: United States Pharmacopeia, 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.
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. 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.
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 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. 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. 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.
See also Trimethylglycine
Amino acid neurotransmitter References
Further reading On attempts to detect glycine in interstellar
medium Kuan YJ, Charnley SB, Huang HC, et al.. "Interstellar
glycine". Astrophys J 593: 848–867. Bibcode:2003ApJ...593..848K. doi:10.1086/375637.
Rachel Nowak. "Amino acid found in deep space - 18 July 2002 - New Scientist". Retrieved
2007-07-01. External links
Glycine MS Spectrum 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.
Guochuan E. Tsai. "A New Class of Antipsychotic Drugs: Enhancing Neurotransmission Mediated
by NMDA Receptors". Psychiatric Times 25. ChemSub Online.
NASA scientists have discovered glycine, a fundamental building block of life, in samples
of comet Wild 2 returned by NASA's Stardust spacecraft.