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
  • 80-68-2 Yes check.svgY
  • 72-19-5(L-isomer) Yes check.svgY
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
DrugBank
ECHA InfoCard 100.000.704 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 201-300-6
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
  • InChI=1S/C4H9NO3/c1-2(6)3(5)4(7)8/h2-3,6H,5H2,1H3,(H,7,8)/t2-,3+/m1/s1
  • Key: AYFVYJQAPQTCCC-GBXIJSLDSA-N
  • C[C@H]([C@@H](C(=O)O)N)O
  • 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
Refractive index (n),
Dielectric constantr), etc.
Thermodynamic
data
Phase behaviour
solidliquidgas
UV, IR, NMR, MS
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)
Infobox references

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 under biological conditions), a carboxyl group (which is in the deprotonated −COO form under biological conditions), 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 second stereoisomer (2S,3S), which is rarely present in nature, is called L-allothreonine. [7] The two stereoisomers (2R,3S)- and (2R,3R)-2-amino-3-hydroxybutanoic acid are only of minor importance. [ citation needed ]

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:

Sources

Foods high in threonine include cottage cheese, poultry, fish, meat, lentils, black turtle bean [15] and sesame seeds. [16]

Racemic threonine can be prepared from crotonic acid by alpha-functionalization using mercury(II) acetate. [17]

Related Research Articles

Protein primary structure Linear sequence of amino acids in a peptide or protein

Protein primary structure is the linear sequence of amino acids in a peptide or protein. By convention, the primary structure of a protein is reported starting from the amino-terminal (N) end to the carboxyl-terminal (C) end. Protein biosynthesis is most commonly performed by ribosomes in cells. Peptides can also be synthesized in the laboratory. Protein primary structures can be directly sequenced, or inferred from DNA sequences.

Protein kinase 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 and the other 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.

Methionine Group of stereoisomers

Methionine is an essential amino acid in humans. As the substrate for other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical role in the metabolism and health of many species, including humans. It is encoded by the codon AUG.

Aspartic acid Amino 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 protonated –NH+
3
form under physiological conditions, while its α-carboxylic acid group is deprotonated −COO under physiological conditions. Aspartic acid has an acidic side chain (CH2COOH) which reacts with other amino acids, enzymes and proteins in the body. Under physiological conditions (pH 7.4) in proteins the side chain usually occurs as the negatively charged aspartate form, −COO. It is a non-essential amino acid in humans, meaning the body can synthesize it as needed. It is encoded by the codons GAT and GAC. In mRNA, CUA and CUG.

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.

Coenzyme A Coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle

Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a substrate, and around 4% of cellular enzymes use it (or a thioester) as a substrate. In humans, CoA biosynthesis requires cysteine, pantothenate (vitamin B5), and adenosine triphosphate (ATP).

Transamination

Transamination, a chemical reaction that transfers an amino group to a ketoacid to form new amino acids. This pathway is responsible for the deamination of most amino acids. This is one of the major degradation pathways which convert essential amino acids to non-essential amino acids.

β-Alanine Chemical compound

β-Alanine is a naturally occurring beta amino acid, which is an amino acid in which the amino group is attached to the β-carbon instead of the more usual α-carbon for alanine (α-alanine). The IUPAC name for β-alanine is 3-aminopropanoic acid. Unlike its counterpart α-alanine, β-alanine has no stereocenter.

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 together 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.

Homoserine 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.

Branched-chain amino acid

A branched-chain amino acid (BCAA) is an amino acid having an aliphatic side-chain with a branch. Among the proteinogenic amino acids, there are three BCAAs: leucine, isoleucine, and valine. Non-proteinogenic BCAAs include 2-aminoisobutyric acid.

Serine/threonine-specific protein kinase

A serine/threonine protein kinase is a kinase enzyme that phosphorylates the OH group of serine or threonine. At least 125 of the 500+ human protein kinases are serine/threonine kinases (STK).

Amino acid synthesis

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 only synthesize 11 of the 20 standard amino acids, and in time of accelerated growth, histidine can be considered an essential amino acid.

Homoserine dehydrogenase

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

Aspartate-semialdehyde dehydrogenase

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.

In enzymology, a [3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)] is an enzyme that catalyzes the chemical reaction

Homoserine kinase

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

Amino acid kinase

In molecular biology, the amino acid kinase domain is a protein domain. It is found in protein kinases with various specificities, including the aspartate, glutamate and uridylate kinase families. In prokaryotes and plants the synthesis of the essential amino acids lysine and threonine is predominantly regulated by feed-back inhibition of aspartate kinase (AK) and dihydrodipicolinate synthase (DHPS). In Escherichia coli, thrA, metLM, and lysC encode aspartokinase isozymes that show feedback inhibition by threonine, methionine, and lysine, respectively. The lysine-sensitive isoenzyme of aspartate kinase from spinach leaves has a subunit composition of 4 large and 4 small subunits.

Non-proteinogenic amino acids

In biochemistry, non-coded or non-proteinogenic amino acids are those not naturally encoded or found in the genetic code of any organism. Despite the use of only 22 amino acids by the translational machinery to assemble proteins, over 140 amino acids are known to occur naturally in proteins and thousands more may occur in nature or be synthesized in the laboratory. Many non-proteinogenic amino acids are noteworthy because they are;

L-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

  1. Dawson, R.M.C., et al., Data for Biochemical Research, Oxford, Clarendon Press, 1959.
  2. "Nomenclature and Symbolism for Amino Acids and Peptides". IUPAC-IUB Joint Commission on Biochemical Nomenclature. 1983. Archived from the original on 9 October 2008. Retrieved 5 March 2018.
  3. Raïs, Badr; Chassagnole, Christophe; Lettelier, Thierry; Fell, David; Mazat, Jean-Pierre (2001). "Threonine synthesis from aspartate in Escherichia coli cell-free extracts: pathway dynamics". J Biochem. 356 (Pt 2): 425–32. doi:10.1042/bj3560425. PMC   1221853 . PMID   11368769.
  4. Jastrzab, Renata (2013). "Studies of new phosphothreonine complexes formed in binary and ternary systems including biogenic amines and copper(II)". Journal of Coordination Chemistry. 66 (1): 98-113. doi:10.1080/00958972.2012.746678
  5. A Dictionary of scientists. Daintith, John., Gjertsen, Derek. Oxford: Oxford University Press. 1999. p. 459. ISBN   9780192800862. OCLC   44963215.CS1 maint: others (link)
  6. Meyer, Curtis (20 July 1936). "The Spatial Configuation of Alpha-Amino-Beta-Hydroxy-n-Butyric Acid" (PDF). Journal of Biological Chemistry. 115 (3): 721–729. doi: 10.1016/S0021-9258(18)74711-X .
  7. "Nomenclature and symbolism for amino acids and peptides (Recommendations 1983)". Pure and Applied Chemistry. 56 (5): 601, 603, 608. 1 January 1984. doi:10.1351/pac198456050595.
  8. Institute of Medicine (2002). "Protein and Amino Acids". Dietary Reference Intakes for Energy, Carbohydrates, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. pp. 589–768.
  9. Lehninger, Albert L.; Nelson, David L.; Cox, Michael M. (2000). Principles of Biochemistry (3rd ed.). New York: W. H. Freeman. ISBN   1-57259-153-6..
  10. Stipanuk, Martha H.; Caudill, Marie A. (2013-08-13). Biochemical, Physiological, and Molecular Aspects of Human Nutrition - E-Book. Elsevier Health Sciences. ISBN   9780323266956.
  11. Bhardwaj, Uma; Bhardwaj, Ravindra. Biochemistry for Nurses. Pearson Education India. ISBN   9788131795286.
  12. Fang, H; Kang, J; Zhang, D (30 January 2017). "Microbial production of vitamin B12: a review and future perspectives". Microbial Cell Factories. 16 (1): 15. doi:10.1186/s12934-017-0631-y. PMC   5282855 . PMID   28137297.
  13. Adeva-Andany, M; Souto-Adeva, G; Ameneiros-Rodríguez, E; Fernández-Fernández, C; Donapetry-García, C; Domínguez-Montero, A (January 2018). "Insulin resistance and glycine metabolism in humans". Amino Acids. 50 (1): 11–27. doi:10.1007/s00726-017-2508-0. PMID   29094215. S2CID   3708658.
  14. Dalangin, R; Kim, A; Campbell, RE (27 August 2020). "The Role of Amino Acids in Neurotransmission and Fluorescent Tools for Their Detection". International Journal of Molecular Sciences. 21 (17): 6197. doi: 10.3390/ijms21176197 . PMC   7503967 . PMID   32867295.
  15. "Error". ndb.nal.usda.gov.
  16. "SELF Nutrition Data - Food Facts, Information & Calorie Calculator". nutritiondata.self.com. Retrieved 27 March 2018.
  17. Carter, Herbert E.; West, Harold D. (1940). "dl-Threonine". Organic Syntheses . 20: 101.; Collective Volume, 3, p. 813.