Threonine (symbol Thr or T) 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 is used in the
biosynthesis
Biosynthesis is a multi-step, enzyme-catalyzed process where substrates are converted into more complex products in living organisms. In biosynthesis, simple compounds are modified, converted into other compounds, or joined to form macromolecul ...
of
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s. It contains an
α-amino group (which is in the protonated −NH form under biological conditions), a
carboxyl group (which is in the deprotonated −COO
− form under biological conditions), and a side chain containing a
hydroxyl group
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy ...
, making it a polar, uncharged amino acid. It is
essential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Threonine is synthesized from
aspartate
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
in bacteria such as
''E. coli''. 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 AC (ACU, ACC, ACA, and ACG).
Threonine sidechains are often hydrogen bonded; the most common small motifs formed are based on interactions with
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 ...
:
ST turn The ST turn is a structural feature in proteins and polypeptides. Each consists of three amino acid residues (labeled ''i'', ''i'' + 1 and ''i'' + 2) in which residue ''i'' is a serine (S) or threonine (T) that forms a hydrog ...
s,
ST motifs (often at the beginning of alpha helices) and
ST staples (usually at the middle of alpha helices).
Modifications
The threonine residue is susceptible to numerous
posttranslational modification
Post-translational modification (PTM) is the covalent and generally enzymatic modification of proteins following protein biosynthesis. This process occurs in the endoplasmic reticulum and the golgi apparatus. Proteins are synthesized by ribos ...
s. The
hydroxyl
In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydrox ...
side-chain can undergo
''O''-linked glycosylation. In addition, threonine residues undergo
phosphorylation
In chemistry, phosphorylation is the attachment of a phosphate group to a molecule or an ion. This process and its inverse, dephosphorylation, are common in biology and could be driven by natural selection. Text was copied from this source, wh ...
through the action of a threonine
kinase
In biochemistry, a kinase () is an enzyme that catalyzes the transfer of phosphate groups from high-energy, phosphate-donating molecules to specific substrates. This process is known as phosphorylation, where the high-energy ATP molecule don ...
. In its phosphorylated form, it can be referred to as
phosphothreonine. Phosphothreonine has three potential coordination sites (carboxyl, amine and phosphate group) and determination of the mode of coordination between phosphorylated ligands and metal ions occurring in an organism is important to explain the function of the phosphothreonine in biological processes.
History
Threonine was the last of the 20 common
proteinogenic
Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) amino ...
amino acids to be discovered. It was discovered in 1936 by
William Cumming Rose, collaborating with Curtis Meyer. The amino acid was named threonine because it was similar in structure to
threonic acid, a four-carbon
monosaccharide
Monosaccharides (from Greek '' monos'': single, '' sacchar'': sugar), also called simple sugars, are the simplest forms of sugar and the most basic units (monomers) from which all carbohydrates are built.
They are usually colorless, water- so ...
with
molecular formula C
4H
8O
5
Stereoisomers
Threonine is one of two proteinogenic amino acids with two
stereogenic centers, the other being
isoleucine
Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the depr ...
. Threonine can exist in four possible
stereoisomers with the following configurations: (2''S'',3''R''), (2''R'',3''S''), (2''S'',3''S'') and (2''R'',3''R''). However, the name
L-threonine is used for one single
stereoisomer, (2''S'',3''R'')-2-amino-3-hydroxybutanoic acid. The second stereoisomer (2''S'',3''S''), which is rarely present in nature, is called
L-allothreonine. The two stereoisomers (2''R'',3''S'')- and (2''R'',3''R'')-2-amino-3-hydroxybutanoic acid are only of minor importance.
Biosynthesis
As an essential amino acid, threonine is not synthesized in humans, and needs to be present in proteins in the diet. Adult humans require about 20 mg/kg body weight/day.
In plants and microorganisms, threonine is synthesized from
aspartic acid
Aspartic acid (symbol Asp or D; the ionic form is known as aspartate), is an α-amino acid that is used in the biosynthesis of proteins. Like all other amino acids, it contains an amino group and a carboxylic acid. Its α-amino group is in the pro ...
via α-aspartyl-semialdehyde and
homoserine. Homoserine undergoes ''O''-phosphorylation; this phosphate
ester
In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ...
undergoes hydrolysis concomitant with relocation of the OH group. Enzymes involved in a typical biosynthesis of threonine include:
#
aspartokinase
Aspartate kinase or aspartokinase (AK) is an enzyme that catalyzes the phosphorylation of the amino acid aspartate. This reaction is the first step in the biosynthesis of three other amino acids: methionine, lysine, and threonine, known as the "as ...
#
β-aspartate semialdehyde dehydrogenase
#
homoserine dehydrogenase
#
homoserine kinase
#
threonine synthase.
Metabolism
Threonine is metabolized in at least three ways:
* In many animals it is 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 ...
via
threonine dehydrogenase. An intermediate in this pathway can undergo
thiolysis with CoA to produce
acetyl-CoA
Acetyl-CoA (acetyl coenzyme A) is a molecule that participates in many biochemical reactions in protein, carbohydrate and lipid metabolism. Its main function is to deliver the acetyl group to the citric acid cycle (Krebs cycle) to be oxidized for ...
and
glycine
Glycine (symbol Gly or G; ) is an amino acid that has a single hydrogen atom as its side chain. It is the simplest stable amino acid ( carbamic acid is unstable), with the chemical formula NH2‐ CH2‐ COOH. Glycine is one of the proteinog ...
.
* In humans the gene for threonine dehydrogenase is an inactive
pseudogene
Pseudogenes are nonfunctional segments of DNA that resemble functional genes. Most arise as superfluous copies of functional genes, either directly by DNA duplication or indirectly by reverse transcription of an mRNA transcript. Pseudogenes ar ...
, so threonine is converted to
α-ketobutyrate. The mechanism of the first step is analogous to that catalyzed 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 ...
, and the serine and threonine dehydratase reactions are probably catalyzed by the same enzyme.
* In many organisms it is
O-phosphorylated by
a kinase preparatory to further metabolism. This is especially important in
bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were am ...
as part of the
biosynthesis of cobalamin (
Vitamin B12), as the product is converted to
(R)-1-aminopropan-2-ol for incorporation into the vitamin's sidechain.
*Threonine is used to synthesize glycine during the endogenous production of L-carnitine in the brain and liver of rats.
Sources
Foods high in threonine include
cottage cheese
Cottage cheese is a curdled milk product with a mild flavor and a creamy, non-homogeneous, soupy texture. It is made from skimmed milk by draining the cheese, as opposed to pressing it to make cheese curd—retaining some of the whey and keep ...
,
poultry
Poultry () are domesticated birds kept by humans for their eggs, their meat or their feathers. These birds are most typically members of the superorder Galloanserae (fowl), especially the order Galliformes (which includes chickens, qu ...
,
fish
Fish are Aquatic animal, aquatic, craniate, gill-bearing animals that lack Limb (anatomy), limbs with Digit (anatomy), digits. Included in this definition are the living hagfish, lampreys, and Chondrichthyes, cartilaginous and bony fish as we ...
,
meat
Meat is animal flesh that is eaten as food. Humans have hunted, farmed, and scavenged animals for meat since prehistoric times. The establishment of settlements in the Neolithic Revolution allowed the domestication of animals such as chic ...
,
lentil
The lentil (''Lens culinaris'' or ''Lens esculenta'') is an edible legume. It is an annual plant known for its lens-shaped seeds. It is about tall, and the seeds grow in pods, usually with two seeds in each. As a food crop, the largest p ...
s,
black turtle bean
The black turtle bean is a small, shiny variety of the common bean (''Phaseolus vulgaris'') especially popular in Latin American cuisine, though it can also be found in the Cajun and Creole cuisines of south Louisiana. Like all varieties of the ...
and
sesame
Sesame ( or ; ''Sesamum indicum'') is a flowering plant in the genus ''Sesamum'', also called benne. Numerous wild relatives occur in Africa and a smaller number in India. It is widely naturalized in tropical regions around the world and is cul ...
seeds.
Racemic threonine can be prepared from
crotonic acid by alpha-functionalization using
mercury(II) acetate
Mercury(II) acetate is the chemical compound with the formula Hg( O2 CC H3)2. Commonly abbreviated Hg(OAc)2, this compound is employed as a reagent to generate organomercury compounds from unsaturated organic precursors. It is a white water-solu ...
.
[.]
References
External links
Threonine biosynthesisCID 205CID 6288
{{Glycinergics
Proteinogenic amino acids
Glucogenic amino acids
Ketogenic amino acids
Essential amino acids
Glycine receptor agonists