Threonine (symbol Thr or T) is an amino acid 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 macromolecules. ...

of proteins. 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 g ...

, 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 − form un ...

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 hydrogen b ...

s, ST motifs (often at the beginning of alpha helices) and

ST staple The ST staple is a common four- or five-amino acid residue motif in proteins and polypeptides with serine or threonine as the C-terminal residue. It is characterized by a single hydrogen bond between the hydroxyl group of the serine or threoni ...

s (usually at the middle of alpha helices).

Modifications

The threonine residue is susceptible to numerous posttranslational modifications. The hydroxyl 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 aci ...

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-solub ...

with molecular formula C₄H₈O₅

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 deprot ...

. 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 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 " ...

# 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 aci ...

via

threonine dehydrogenase In enzymology, a L-threonine 3-dehydrogenase () is an enzyme that catalyzes the chemical reaction :L-threonine + NAD+ \rightleftharpoons L-2-amino-3-oxobutanoate + NADH + H+ Thus, the two substrates of this enzyme are L-threonine and NAD+, ...

. 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. * 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 transcriptase, reverse transcription of an mRNA trans ...

, 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 the ...

, 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 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, poultry, fish,

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 ...

, lentils,

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 th ...

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 cu ...

seeds. Racemic threonine can be prepared from crotonic acid by alpha-functionalization using mercury(II) acetate..

References

External links

Threonine biosynthesisCID 205CID 6288
{{Glycinergics Proteinogenic amino acids Glucogenic amino acids Ketogenic amino acids Essential amino acids Glycine receptor agonists