Threonine

Last updated
Threonine
L-Threonin - L-Threonine.svg
Skeletal formula of L-threonine
Ball-and-stick model Threonine-from-xtal-3D-bs-17.png
Ball-and-stick model
Space-filling model Threonine-from-xtal-3D-sf.png
Space-filling model
Names
IUPAC name
Threonine
Other names
2-Amino-3-hydroxybutanoic acid
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.704 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • L:200-774-1
KEGG
PubChem CID
UNII
  • InChI=1S/C4H9NO3/c1-2(6)3(5)4(7)8/h2-3,6H,5H2,1H3,(H,7,8)/t2-,3+/m1/s1 Yes check.svgY
    Key: AYFVYJQAPQTCCC-GBXIJSLDSA-N Yes check.svgY
  • D/L:Key: AYFVYJQAPQTCCC-FGNFWGHYNA-N
  • L:C[C@H]([C@@H](C(=O)O)N)O
  • L Zwitterion:C[C@H]([C@@H](C(=O)[O-])[NH3+])O
Properties
C4H9NO3
Molar mass 119.120 g·mol−1
(H2O, g/dl) 10.6(30°),14.1(52°),19.0(61°)
Acidity (pKa)2.63 (carboxyl), 10.43 (amino) [1]
Supplementary data page
Threonine (data page)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).

Threonine (symbol Thr or T) [2] is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH+
3
form when dissolved in water), a carboxyl group (which is in the deprotonated −COO form when dissolved in water), and a side chain containing a hydroxyl group, 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 in bacteria such as E. coli. [3] It is encoded by all the codons starting AC (ACU, ACC, ACA, and ACG).

Contents

Threonine sidechains are often hydrogen bonded; the most common small motifs formed are based on interactions with serine: ST turns, 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 modifications. The hydroxyl side-chain can undergo O-linked glycosylation. In addition, threonine residues undergo phosphorylation through the action of a threonine kinase. 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. [4]

History

Threonine was the last of the 20 common proteinogenic amino acids to be discovered. It was discovered in 1936 by William Cumming Rose, [5] collaborating with Curtis Meyer. The amino acid was named threonine because it was similar in structure to threonic acid, a four-carbon monosaccharide with molecular formula C4H8O5 [6]

Stereoisomers

L-Threonin - L-Threonine.svg   D-Threonine.svg
L-Threonine (2S,3R) and D-Threonine (2R,3S)
L-allo-Threonine.svg   D-allo-Threonine.svg
L-Allothreonine (2S,3S) and D-Allothreonine (2R,3R)

Threonine is one of two proteinogenic amino acids with two stereogenic centers, the other being isoleucine. Threonine can exist in four possible stereoisomers with the following configurations: (2S,3R), (2R,3S), (2S,3S) and (2R,3R). However, the name L-threonine is used for one single stereoisomer, (2S,3R)-2-amino-3-hydroxybutanoic acid. The stereoisomer (2S,3S), which is rarely present in nature, is called L-allothreonine. [7]

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. [8] In plants and microorganisms, threonine is synthesized from aspartic acid via α-aspartyl-semialdehyde and homoserine. Homoserine undergoes O-phosphorylation; this phosphate ester undergoes hydrolysis concomitant with relocation of the OH group. [9] Enzymes involved in a typical biosynthesis of threonine include:

  1. aspartokinase
  2. β-aspartate semialdehyde dehydrogenase
  3. homoserine dehydrogenase
  4. homoserine kinase
  5. threonine synthase.
Threonine biosynthesis Threonine biosynthesis.svg
Threonine biosynthesis

Metabolism

Threonine is metabolized in at least three ways:

Metabolic diseases

The degradation of threonine is impaired in the following metabolic diseases:

Research of Threonine as a Dietary Supplement in Animals

Effects of threonine dietary supplementation have been researched in broilers. [17]

An essential amino acid, threonine is involved in the metabolism of fats, the creation of proteins, the proliferation and differentiation of embryonic stem cells, and the health and function of the intestines. Animal health and illness are strongly correlated with the need for and metabolism of threonine. Intestinal inflammation and energy metabolism disorders in animals may be alleviated by appropriate amounts of dietary threonine. Nevertheless, because these effects pertain to the control of nutrition metabolism, more research is required to confirm the results in various animal models. Furthermore, more research is needed to understand how threonine controls the dynamic equilibrium of the intestinal barrier function, immunological response and gut flora. [18]

Sources

Foods high in threonine include cottage cheese, poultry, fish, meat, lentils, black turtle bean [19] and sesame seeds. [20]

Racemic threonine can be prepared from crotonic acid by alpha-functionalization using mercury(II) acetate. [21]

Related Research Articles

<span class="mw-page-title-main">Amino acid</span> Organic compounds containing amine and carboxylic groups

Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although over 500 amino acids exist in nature, by far the most important are the 22 α-amino acids incorporated into proteins. Only these 22 appear in the genetic code of life.

<span class="mw-page-title-main">Glycine</span> Amino acid

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). In the gas phase, it is a molecule with the chemical formula NH2CH2‐COOH. In solution or in the solid, glycine exists as the zwitterion. Glycine is one of the proteinogenic amino acids. It is encoded by all the codons starting with GG (GGU, GGC, GGA, GGG). Glycine is integral to the formation of alpha-helices in secondary protein structure due to the "flexibility" caused by such a small R group. Glycine is also an inhibitory neurotransmitter – interference with its release within the spinal cord (such as during a Clostridium tetani infection) can cause spastic paralysis due to uninhibited muscle contraction.

<span class="mw-page-title-main">Protein kinase</span> Enzyme that adds phosphate groups to other proteins

A protein kinase is a kinase which selectively modifies other proteins by covalently adding phosphates to them (phosphorylation) as opposed to kinases which modify lipids, carbohydrates, or other molecules. Phosphorylation usually results in a functional change of the target protein (substrate) by changing enzyme activity, cellular location, or association with other proteins. The human genome contains about 500 protein kinase genes and they constitute about 2% of all human genes. There are two main types of protein kinase. The great majority are serine/threonine kinases, which phosphorylate the hydroxyl groups of serines and threonines in their targets. Most of the others are tyrosine kinases, although additional types exist. Protein kinases are also found in bacteria and plants. Up to 30% of all human proteins may be modified by kinase activity, and kinases are known to regulate the majority of cellular pathways, especially those involved in signal transduction.

<span class="mw-page-title-main">Methionine</span> Sulfur-containing amino acid

Methionine is an essential amino acid in humans.

<span class="mw-page-title-main">Isoleucine</span> Chemical compound

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+3 form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO form under biological conditions), and a hydrocarbon side chain with a branch (a central carbon atom bound to three other carbon atoms). It is classified as a non-polar, uncharged (at physiological pH), branched-chain, aliphatic amino acid. It is essential in humans, meaning the body cannot synthesize it. Essential amino acids are necessary in the human diet. In plants isoleucine can be synthesized from threonine and methionine. In plants and bacteria, isoleucine is synthesized from pyruvate employing leucine biosynthesis enzymes. It is encoded by the codons AUU, AUC, and AUA.

<span class="mw-page-title-main">Lysine</span> Amino acid

Lysine (symbol Lys or K) is an α-amino acid that is a precursor to many proteins. It contains an α-amino group (which is in the protonated −NH+
3
form when dissolved in water), an α-carboxylic acid group (which is in the deprotonated −COO form when dissolved in water), and a side chain lysyl ((CH2)4NH2), classifying it as a basic, charged (at physiological pH), aliphatic amino acid. It is encoded by the codons AAA and AAG. Like almost all other amino acids, the α-carbon is chiral and lysine may refer to either enantiomer or a racemic mixture of both. For the purpose of this article, lysine will refer to the biologically active enantiomer L-lysine, where the α-carbon is in the S configuration.

Serine is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, a carboxyl group, and a side chain consisting of a hydroxymethyl group, classifying it as a polar amino acid. It can be synthesized in the human body under normal physiological circumstances, making it a nonessential amino acid. It is encoded by the codons UCU, UCC, UCA, UCG, AGU and AGC.

Valine (symbol Val or V) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH3+ form under biological conditions), an α-carboxylic acid group (which is in the deprotonated −COO form under biological conditions), and a side chain isopropyl group, making it a non-polar aliphatic amino acid. Valine is essential in humans, meaning the body cannot synthesize it; it must be obtained from dietary sources which are foods that contain proteins, such as meats, dairy products, soy products, beans and legumes. It is encoded by all codons starting with GU (GUU, GUC, GUA, and GUG).

An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life forms, the nine amino acids humans cannot synthesize are valine, isoleucine, leucine, methionine, phenylalanine, tryptophan, threonine, histidine, and lysine.

Propionic acidemia, also known as propionic aciduria or propionyl-CoA carboxylase deficiency, is a rare autosomal recessive metabolic disorder, classified as a branched-chain organic acidemia.

<span class="mw-page-title-main">Pyridoxal phosphate</span> Active form of vitamin B6

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 activities, corresponding to ~4% of all classified activities. The versatility of PLP arises from its ability to covalently bind the substrate, and then to act as an electrophilic catalyst, thereby stabilizing different types of carbanionic reaction intermediates.

In molecular biology, 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. This process often consists of metabolic pathways. Some of these biosynthetic pathways are located within a single cellular organelle, while others involve enzymes that are located within multiple cellular organelles. Examples of these biosynthetic pathways include the production of lipid membrane components and nucleotides. Biosynthesis is usually synonymous with anabolism.

<span class="mw-page-title-main">Homoserine</span> Chemical compound

Homoserine (also called isothreonine) is an α-amino acid with the chemical formula HO2CCH(NH2)CH2CH2OH. L-Homoserine is not one of the common amino acids encoded by DNA. It differs from the proteinogenic amino acid serine by insertion of an additional -CH2- unit into the backbone. Homoserine, or its lactone form, is the product of a cyanogen bromide cleavage of a peptide by degradation of methionine.

<span class="mw-page-title-main">Methylmalonyl-CoA mutase deficiency</span> Medical condition

Methylmalonyl-CoA mutase is a mitochondrial homodimer apoenzyme that focuses on the catalysis of methylmalonyl CoA to succinyl CoA. The enzyme is bound to adenosylcobalamin, a hormonal derivative of vitamin B12 in order to function. Methylmalonyl-CoA mutase deficiency is caused by genetic defect in the MUT gene responsible for encoding the enzyme. Deficiency in this enzyme accounts for 60% of the cases of methylmalonic acidemia.

<span class="mw-page-title-main">Amino acid synthesis</span> The set of biochemical processes by which amino acids are produced

Amino acid synthesis is the set of biochemical processes by which the amino acids are produced. The substrates for these processes are various compounds in the organism's diet or growth media. Not all organisms are able to synthesize all amino acids. For example, humans can synthesize 11 of the 20 standard amino acids. These 11 are called the non-essential amino acids).

<span class="mw-page-title-main">Homoserine dehydrogenase</span> Enzyme

In enzymology, a homoserine dehydrogenase (EC 1.1.1.3) is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Aspartate-semialdehyde dehydrogenase</span> Amino-acid-synthesizing enzyme in fungi, plants and prokaryota

In enzymology, an aspartate-semialdehyde dehydrogenase is an enzyme that is very important in the biosynthesis of amino acids in prokaryotes, fungi, and some higher plants. It forms an early branch point in the metabolic pathway forming lysine, methionine, leucine and isoleucine from aspartate. This pathway also produces diaminopimelate which plays an essential role in bacterial cell wall formation. There is particular interest in ASADH as disabling this enzyme proves fatal to the organism giving rise to the possibility of a new class of antibiotics, fungicides, and herbicides aimed at inhibiting it.

<span class="mw-page-title-main">Homoserine kinase</span> Enzyme

In enzymology, a homoserine kinase is an enzyme that catalyzes the chemical reaction

<span class="mw-page-title-main">Glycine betaine aldehyde</span> Chemical compound

Glycine betaine aldehyde, often simply called betaine aldehyde, is an intermediate in the metabolism of glycine, serine and threonine. The human aldehyde dehydrogenase stimulates the transformation of betaine aldehyde to glycine betaine. Betaine aldehyde is a substrate for choline dehydrogenase (mitochondrial).

<small>L</small>-Aspartic-4-semialdehyde Chemical compound

L-Aspartic-4-semialdehyde is an α-amino acid derivative of aspartate. It is an important intermediate in the aspartate pathway, which is a metabolic pathway present in bacteria and plants. The aspartate pathway leads to the biosynthesis of a variety of amino acids from aspartate, including lysine, methionine, and threonine.

References

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