Glycine (symbol Gly or G; ) is an
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...
that has a single
hydrogen
Hydrogen is the chemical element with the symbol H and atomic number 1. Hydrogen is the lightest element. At standard conditions hydrogen is a gas of diatomic molecules having the formula . It is colorless, odorless, tasteless, non-to ...
atom as its
side chain. It is the simplest stable amino acid (
carbamic acid is unstable), with the
chemical formula
In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, ...
NH2‐
CH2‐
COOH. Glycine is one of the
proteinogenic amino acids. It is
encoded by all the
codon
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
s starting with GG (GGU, GGC, GGA, GGG). Glycine is integral to the formation of
alpha-helices in
secondary protein structure due to its compact form. For the same reason, it is the most abundant amino acid in
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whol ...
triple-helices. Glycine is also an inhibitory
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neu ...
– interference with its release within the spinal cord (such as during a ''
Clostridium tetani
''Clostridium tetani'' is a common soil bacterium and the causative agent of tetanus. Vegetative cells of ''Clostridium tetani'' are usually rod-shaped and up to 2.5 μm long, but they become enlarged and tennis racket- or drumstick-shaped when ...
'' infection) can cause
spastic paralysis due to uninhibited muscle contraction.
It is the only
achiral
Chirality is a property of asymmetry important in several branches of science. The word ''chirality'' is derived from the Greek (''kheir''), "hand", a familiar chiral object.
An object or a system is ''chiral'' if it is distinguishable from i ...
proteinogenic amino acid. It can fit into
hydrophilic
A hydrophile is a molecule or other molecular entity that is attracted to water molecules and tends to be dissolved by water.Liddell, H.G. & Scott, R. (1940). ''A Greek-English Lexicon'' Oxford: Clarendon Press.
In contrast, hydrophobes are n ...
or
hydrophobic
In chemistry, hydrophobicity is the physical property of a molecule that is seemingly repelled from a mass of water (known as a hydrophobe). In contrast, hydrophiles are attracted to water.
Hydrophobic molecules tend to be nonpolar and, ...
environments, due to its minimal side chain of only one hydrogen atom.
History and etymology
Glycine was discovered in 1820 by the French chemist
Henri Braconnot when he hydrolyzed
gelatin
Gelatin or gelatine (from la, gelatus meaning "stiff" or "frozen") is a translucent, colorless, flavorless food ingredient, commonly derived from collagen taken from animal body parts. It is brittle when dry and rubbery when moist. It may also ...
by boiling it with
sulfuric acid
Sulfuric acid (American spelling and the preferred IUPAC name) or sulphuric acid ( Commonwealth spelling), known in antiquity as oil of vitriol, is a mineral acid composed of the elements sulfur, oxygen and hydrogen, with the molecular fo ...
. He originally called it "sugar of gelatin", but the French chemist
Jean-Baptiste Boussingault
Jean-Baptiste Joseph Dieudonné Boussingault (2 February 1801 – 11 May 1887) was a French chemist who made significant contributions to agricultural science, petroleum science and metallurgy.
Biography
Jean-Baptiste Boussingault – an agric ...
showed that it contained nitrogen. The American scientist
Eben Norton Horsford, then a student of the German chemist
Justus von Liebig
Justus Freiherr von Liebig (12 May 1803 – 20 April 1873) was a German scientist who made major contributions to agricultural and biological chemistry, and is considered one of the principal founders of organic chemistry. As a professor at th ...
, proposed the name "glycocoll"; however, the
Swedish chemist
Berzelius suggested the simpler name "glycine". The name comes from the
Greek word γλυκύς "sweet tasting" (which is also related to the prefixes ''
glyco-'' and ''
gluco-'', as in ''
glycoprotein
Glycoproteins are proteins which contain oligosaccharide chains covalently attached to amino acid side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glyco ...
'' and ''
glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, u ...
''). In 1858, the French chemist
Auguste Cahours determined that glycine was an
amine
In chemistry, amines (, ) are compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are formally derivatives of ammonia (), wherein one or more hydrogen atoms have been replaced by a substituent ...
of
acetic acid
Acetic acid , systematically named ethanoic acid , is an acidic, colourless liquid and organic compound with the chemical formula (also written as , , or ). Vinegar is at least 4% acetic acid by volume, making acetic acid the main componen ...
.
Production
Although glycine can be isolated from hydrolyzed protein, this route is not used for industrial production, as it can be manufactured more conveniently by chemical synthesis. The two main processes are amination of
chloroacetic acid with
ammonia
Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictogen hydride, ammonia is a colourless gas with a distinct pungent smell. Biologically, it is a common nitrogenous ...
, giving glycine and
ammonium chloride, and the
Strecker amino acid synthesis
The Strecker amino acid synthesis, also known simply as the Strecker synthesis, is a method for the synthesis of amino acids by the reaction of an aldehyde with ammonia in the presence of potassium cyanide. The condensation reaction yields an α- ...
, which is the main synthetic method in the United States and Japan.
About 15 thousand
tonne
The tonne ( or ; symbol: t) is a unit of mass equal to 1000 kilograms. It is a non-SI unit accepted for use with SI. It is also referred to as a metric ton to distinguish it from the non-metric units of the short ton ( United State ...
s are produced annually in this way.
Glycine is also cogenerated as an impurity in the synthesis of
EDTA, arising from reactions of the ammonia coproduct.
Chemical reactions
Its acid–base properties are most important. In aqueous solution, glycine is
amphoteric: below pH = 2.4, it converts to the ammonium cation called glycinium. Above about 9.6, it converts to glycinate.
:
Glycine functions as a
bidentate ligand
In coordination chemistry, a ligand is an ion or molecule (functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's electro ...
for many metal ions, forming
amino acid complexes. A typical complex is Cu(glycinate)
2, i.e. Cu(H
2NCH
2CO
2)
2, which exists both in cis and trans isomers.
With acid chlorides, glycine converts to the amidocarboxylic acid, such as
hippuric acid
Hippuric acid ( Gr. ''hippos'', horse, ''ouron'', urine) is a carboxylic acid and organic compound. It is found in urine and is formed from the combination of benzoic acid and glycine. Levels of hippuric acid rise with the consumption of phenolic ...
and
acetylglycine. With
nitrous acid, one obtains
glycolic acid (
van Slyke determination The Van Slyke determination is a chemical test for the determination of amino acids containing a primary amine group. It is named after the biochemist Donald Dexter Van Slyke (1883-1971).
One of Van Slyke's first professional achievements was the ...
). With
methyl iodide
Iodomethane, also called methyl iodide, and commonly abbreviated "MeI", is the chemical compound with the formula CH3I. It is a dense, colorless, volatile liquid. In terms of chemical structure, it is related to methane by replacement of one ...
, the amine becomes quaternized to give
trimethylglycine, a natural product:
: + 3 CH
3I → + 3 HI
Glycine condenses with itself to give peptides, beginning with the formation of
glycylglycine:
:2 → + H
2O
Pyrolysis of glycine or glycylglycine gives
2,5-diketopiperazine, the cyclic diamide.
It forms esters with alcohols. They are often isolated as their
hydrochloride, e.g.,
glycine methyl ester hydrochloride. Otherwise the free ester tends to convert to
diketopiperazine
A diketopiperazine (DKP), also known as a ''dioxopiperazine'' or ''piperazinedione'', is a class of organic compounds related to piperazine but containing two amide linkages. DKP's are the smallest known class of cyclic peptide. Despite their name, ...
.
As a bifunctional molecule, glycine reacts with many reagents. These can be classified into N-centered and carboxylate-center reactions.
Metabolism
Biosynthesis
Glycine is not
essential to the human diet, as it is biosynthesized in the body from the amino acid
serine
Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α- amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − for ...
, which is in turn derived from
3-phosphoglycerate, but the metabolic capacity for glycine biosynthesis does not satisfy the need for collagen synthesis. In most organisms, the enzyme
serine hydroxymethyltransferase catalyses this transformation via the cofactor
pyridoxal phosphate
Pyridoxal phosphate (PLP, pyridoxal 5'- phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent ...
:
: serine +
tetrahydrofolate → glycine +
''N5'',''N10''-methylene tetrahydrofolate + H
2O
In the liver of
vertebrate
Vertebrates () comprise all animal taxa within the subphylum Vertebrata () ( chordates with backbones), including all mammals, birds, reptiles, amphibians, and fish. Vertebrates represent the overwhelming majority of the phylum Chordata, with ...
s, glycine synthesis is catalyzed by
glycine synthase
The glycine cleavage system (GCS) is also known as the glycine decarboxylase complex or GDC. The system is a series of enzymes that are triggered in response to high concentrations of the amino acid glycine. The same set of enzymes is sometimes r ...
(also called glycine cleavage enzyme). This conversion is readily
reversible:
: CO
2 + NH + ''N
5'',''N
10''-methylene tetrahydrofolate + NADH + H
+ ⇌ Glycine + tetrahydrofolate + NAD
+
In addition to being synthesized from serine, glycine can also be derived from
threonine,
choline or hydroxyproline via inter-organ metabolism of the liver and kidneys.
Degradation
Glycine is degraded via three pathways. The predominant pathway in animals and plants is the reverse of the glycine synthase pathway mentioned above. In this context, the enzyme system involved is usually called the
glycine cleavage system
The glycine cleavage system (GCS) is also known as the glycine decarboxylase complex or GDC. The system is a series of enzymes that are triggered in response to high concentrations of the amino acid glycine. The same set of enzymes is sometimes r ...
:
: Glycine + tetrahydrofolate + NAD
+ ⇌ CO
2 + NH + ''N
5'',''N
10''-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
Pyruvic acid (CH3COCOOH) is the simplest of the alpha-keto acids, with a carboxylic acid and a ketone functional group. Pyruvate, the conjugate base, CH3COCOO−, is an intermediate in several metabolic pathways throughout the cell.
Pyruvic a ...
by
serine dehydratase
Serine dehydratase or L-serine ammonia lyase (SDH) is in the β-family of pyridoxal phosphate-dependent (PLP) enzymes. SDH is found widely in nature, but its structural and properties vary among species. SDH is found in yeast, bacteria, and th ...
.
In the third pathway of its degradation, glycine is converted to
glyoxylate
Glyoxylic acid or oxoacetic acid is an organic compound. Together with acetic acid, glycolic acid, and oxalic acid, glyoxylic acid is one of the C2 carboxylic acids. It is a colourless solid that occurs naturally and is useful industrially.
Str ...
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 varied between 0.5 and 4.0 hours.
Glycine is extremely sensitive to antibiotics which target folate, and blood glycine levels drop severely within a minute of antibiotic injections. Some antibiotics can deplete more than 90% of glycine within a few minutes of being administered.
Physiological function
The principal function of glycine is it acts as a
precursor to proteins. Most proteins incorporate only small quantities of glycine, a notable exception being
collagen
Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whol ...
, which contains about 35% glycine due to its periodically repeated role in the formation of collagen's helix structure in conjunction with
hydroxyproline
(2''S'',4''R'')-4-Hydroxyproline, or L-hydroxyproline ( C5 H9 O3 N), is an amino acid, abbreviated as Hyp or O, ''e.g.'', in Protein Data Bank.
Structure and discovery
In 1902, Hermann Emil Fischer isolated hydroxyproline from hydrolyzed gelatin ...
.
In the
genetic code, glycine is coded by all
codons
The genetic code is the set of rules used by living cells to translate information encoded within genetic material ( DNA or RNA sequences of nucleotide triplets, or codons) into proteins. Translation is accomplished by the ribosome, which links ...
starting with GG, namely GGU, GGC, GGA and GGG.
As a biosynthetic intermediate
In higher
eukaryotes
Eukaryotes () are organisms whose cells have a nucleus. All animals, plants, fungi, and many unicellular organisms, are Eukaryotes. They belong to the group of organisms Eukaryota or Eukarya, which is one of the three domains of life. Bacter ...
,
δ-aminolevulinic acid, the key precursor to
porphyrins, is biosynthesized from glycine and
succinyl-CoA by the enzyme
ALA synthase
Aminolevulinic acid synthase (ALA synthase, ALAS, or delta-aminolevulinic acid synthase) is an enzyme () that catalyzes the synthesis of δ-aminolevulinic acid (ALA) the first common precursor in the biosynthesis of all tetrapyrroles such as hemes ...
. Glycine provides the central C
2N subunit of all
purine
Purine is a heterocyclic aromatic organic compound that consists of two rings ( pyrimidine and imidazole) fused together. It is water-soluble. Purine also gives its name to the wider class of molecules, purines, which include substituted purines ...
s.
As a neurotransmitter
Glycine is an inhibitory
neurotransmitter
A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell.
Neu ...
in the
central nervous system
The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all p ...
, especially in the
spinal cord
The spinal cord is a long, thin, tubular structure made up of nervous tissue, which extends from the medulla oblongata in the brainstem to the lumbar region of the vertebral column (backbone). The backbone encloses the central canal of the sp ...
,
brainstem
The brainstem (or brain stem) is the posterior stalk-like part of the brain that connects the cerebrum with the spinal cord. In the human brain the brainstem is composed of the midbrain, the pons, and the medulla oblongata. The midbrain is ...
, and
retina
The retina (from la, rete "net") is the innermost, light-sensitive layer of tissue of the eye of most vertebrates and some molluscs. The optics of the eye create a focused two-dimensional image of the visual world on the retina, which the ...
. When
glycine receptors are activated,
chloride
The chloride ion is the anion (negatively charged ion) Cl−. It is formed when the element chlorine (a halogen) gains an electron or when a compound such as hydrogen chloride is dissolved in water or other polar solvents. Chloride s ...
enters the neuron via ionotropic receptors, causing an
inhibitory postsynaptic potential (IPSP).
Strychnine
Strychnine (, , US chiefly ) is a highly toxic, colorless, bitter, crystalline alkaloid used as a pesticide, particularly for killing small vertebrates such as birds and rodents. Strychnine, when inhaled, swallowed, or absorbed through the e ...
is a strong antagonist at ionotropic glycine receptors, whereas
bicuculline
Bicuculline is a phthalide-isoquinoline compound that is a light-sensitive competitive antagonist of GABAA receptors. It was originally identified in 1932 in plant alkaloid extracts and has been isolated from '' Dicentra cucullaria'', ''Adlumia ...
is a weak one. Glycine is a required
co-agonist along with
glutamate
Glutamic acid (symbol Glu or E; the ionic form is known as glutamate) is an α-amino acid that is used by almost all living beings in the biosynthesis of proteins. It is a non-essential nutrient for humans, meaning that the human body can synt ...
for
NMDA receptor
The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other two being AMPA and ...
s. In contrast to the inhibitory role of glycine in the spinal cord, this behaviour is facilitated at the (
NMDA)
glutamatergic receptors which are excitatory. The of glycine is 7930 mg/kg in rats (oral), and it usually causes death by hyperexcitability.
Uses
In the US, glycine is typically sold in two grades:
United States Pharmacopeia (“USP”), and technical grade. USP grade sales account for approximately 80 to 85 percent of the U.S. market for glycine. If purity greater than the USP standard is needed, for example for
intravenous
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
injections, a more expensive pharmaceutical grade glycine can be used. Technical grade glycine, which may or may not meet USP grade standards, is sold at a lower price for use in industrial applications, e.g., as an agent in metal complexing and finishing.
Animal and human foods
Glycine is not widely used in foods for its nutritional value, except in infusions. Instead glycine's role in food chemistry is as a flavorant. It is mildly sweet, and it counters the aftertaste of
saccharine
Saccharin (''aka'' saccharine, Sodium sacchari) is an artificial sweetener with effectively no nutritional value. It is about 550 times as sweet as sucrose but has a bitter or metallic aftertaste, especially at high concentrations. Saccharin is ...
. It also has preservative properties, perhaps owing to its complexation to metal ions. Metal glycinate complexes, e.g.
copper(II) glycinate are used as supplements for animal feeds.
[
The U.S. "Food and Drug Administration no longer regards glycine and its salts as generally recognized as safe for use in human food".
]
Chemical feedstock
Glycine is an intermediate in the synthesis of a variety of chemical products. It is used in the manufacture of the herbicide
Herbicides (, ), also commonly known as weedkillers, are substances used to control undesired plants, also known as weeds.EPA. February 201Pesticides Industry. Sales and Usage 2006 and 2007: Market Estimates. Summary in press releasMain page f ...
s glyphosate, iprodione, glyphosine, imiprothrin
Imiprothrin is a synthetic pyrethroid insecticide. It is an ingredient in some commercial and consumer insecticide products for indoor use. It has low acute toxicity to humans through the inhalation and dermal routes, but to insects it acts as a n ...
, and eglinazine.[ It is used as an intermediate of the medicine such as ]thiamphenicol
Thiamphenicol (also known as thiophenicol and dextrosulphenidol) is an antibiotic. It is the methyl-sulfonyl analogue of chloramphenicol and has a similar spectrum of activity, but is 2.5 to 5 times as potent. Like chloramphenicol, it is insolubl ...
.
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
The western blot (sometimes called the protein immunoblot), or western blotting, is a widely used analytical technique in molecular biology and immunogenetics to detect specific proteins in a sample of tissue homogenate or extract. Besides detect ...
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 presence of glycine outside the earth was confirmed in 2009, based on the analysis of samples that had been taken in 2004 by the NASA
The National Aeronautics and Space Administration (NASA ) is an independent agency of the US federal government responsible for the civil space program, aeronautics research, and space research.
NASA was established in 1958, succeedin ...
spacecraft ''Stardust
Stardust may refer to:
* A type of cosmic dust, composed of particles in space
Entertainment Songs
* “Stardust” (1927 song), by Hoagy Carmichael
* “Stardust” (David Essex song), 1974
* “Stardust” (Lena Meyer-Landrut song), 2012
* ...
'' from comet Wild 2
Comet 81P/Wild, also known as Wild 2 (pronounced "vilt two") ( ), is a comet named after Swiss astronomer Paul Wild, who discovered it on January 6, 1978, using a 40-cm Schmidt telescope at Zimmerwald, Switzerland.
For most of its 4.5 billion- ...
and subsequently returned to earth. Glycine had previously been identified in the Murchison meteorite in 1970. The discovery of glycine in outer space bolstered the hypothesis of so called soft-panspermia, which claims that the "building blocks" of life are widespread throughout the universe. In 2016, detection of glycine within Comet 67P/Churyumov–Gerasimenko by the ''Rosetta'' spacecraft was announced.
The detection of glycine outside the Solar System
The Solar System Capitalization of the name varies. The International Astronomical Union, the authoritative body regarding astronomical nomenclature, specifies capitalizing the names of all individual astronomical objects but uses mixed "Solar ...
in the interstellar medium
In astronomy, the interstellar medium is the matter and radiation that exist in the space between the star systems in a galaxy. This matter includes gas in ionic, atomic, and molecular form, as well as dust and cosmic rays. It fills interstella ...
has been debated. In 2008, the Max Planck Institute for Radio Astronomy discovered the spectral lines of a glycine precursor ( aminoacetonitrile) in the Large Molecule Heimat, a giant gas cloud near the galactic center in the constellation Sagittarius.
Evolution
Glycine is proposed to be defined by early genetic codes. For example, low complexity regions (in proteins), that may resemble the proto-peptides of the early genetic code are highly enriched in glycine.
Presence in foods
See also
* Trimethylglycine
* Amino acid neurotransmitter
An amino acid neurotransmitter is an amino acid which is able to transmit a nerve message across a synapse. Neurotransmitters (chemicals) are packaged into vesicles that cluster beneath the axon terminal membrane on the presynaptic side of a sy ...
References
Further reading
*
*
External links
Glycine MS Spectrum
*
*
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Glucogenic amino acids
Inhibitory amino acids
Proteinogenic amino acids
Glycine receptor agonists
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