Threonine

Last updated
Threonine
Skeletal formula L-Threonin - L-Threonine.svg
Skeletal formula
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
Systematic IUPAC name
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. [4] [5] 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. [6]

History

Threonine was the last of the 20 common proteinogenic amino acids to be discovered. It was discovered in 1935 by William Cumming Rose, [7] 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 [8]

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. [9]

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. [10] 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. [11] 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. [19]

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. [20]

Exploration of L-Threonine for Tuberculosis

With multidrug-resistant Mycobacterium tuberculosis (TB) remaining a public health crisis with a total of 1.25 million people dead worldwide from TB in 2023 alone, new treatment strategies for TB are critical. [21] TB is an airborne infection, spread via inhalation of airborne droplets that can remain suspended in the air for several hours, and can either be killed, remain in a latent stage, or become active. One previous paper researched the inhibitory effects of the downstream product L-threonine on the homoserine kinase (HSK) pathway in Escherichia coli. They found that the HSK pathway can be successfully inhibited via L-threonine since the pathway acts as a negative feedback loop, becoming inhibited once enough of the product is formed. [22] Investigation of this pathway in TB may yield new insights into potential drug targets. Inhibiting the fatty acid synthesis pathway as well could serve as a potential drug target since this pathway is responsible for synthesizing mycolic acids, components necessary for formation of TB’s cell walls. [23] Coupling of the amino acid L-threonine with a common TB drug that inhibits fatty acid synthesis, like ethionamide, could yield a new treatment strategy for tuberculosis.

Sources

Foods high in threonine include cottage cheese, poultry, fish, meat, lentils, black turtle bean [24] and sesame seeds. [25]

Racemic threonine can be prepared from crotonic acid by alpha-functionalization using mercury(II) acetate. [26]

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". Biochem J. 356 (Pt 2): 425–32. doi:10.1042/bj3560425. PMC   1221853 . PMID   11368769.
  4. ↑ Walsh, Christopher T.; Garneau-Tsodikova, Sylvie; Gatto, Gregory J. (2005-11-18). "Protein Posttranslational Modifications: The Chemistry of Proteome Diversifications". Angewandte Chemie International Edition. 44 (45): 7342–7372. doi:10.1002/anie.200501023. PMID   16267872.
  5. ↑ Millar, A. Harvey; Heazlewood, Joshua L.; Giglione, Carmela; Holdsworth, Michael J.; Bachmair, Andreas; Schulze, Waltraud X. (2019-04-29). "The Scope, Functions, and Dynamics of Posttranslational Protein Modifications". Annual Review of Plant Biology. 70 (1): 119–151. Bibcode:2019AnRPB..70..119M. doi:10.1146/annurev-arplant-050718-100211. ISSN   1543-5008. PMID   30786234.
  6. ↑ 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.
  7. ↑ A Dictionary of scientists. Daintith, John., Gjertsen, Derek. Oxford: Oxford University Press. 1999. p. 459. ISBN   9780192800862. OCLC   44963215.{{cite book}}: CS1 maint: others (link)
  8. ↑ 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 .
  9. ↑ "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 .
  10. ↑ 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. doi:10.17226/10490. ISBN   978-0-309-08525-0.
  11. ↑ 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..
  12. ↑ Stipanuk, Martha H.; Caudill, Marie A. (2013). Biochemical, Physiological, and Molecular Aspects of Human Nutrition – E-Book. Elsevier Health Sciences. ISBN   9780323266956.
  13. ↑ Bhardwaj, Uma; Bhardwaj, Ravindra. Biochemistry for Nurses. Pearson Education India. ISBN   9788131795286.
  14. ↑ 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.
  15. ↑ 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.
  16. ↑ 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.
  17. 1 2 Manoli, Irini; Sloan, Jennifer L.; Venditti, Charles P. (1993), Adam, Margaret P.; Feldman, Jerry; Mirzaa, Ghayda M.; Pagon, Roberta A. (eds.), "Isolated Methylmalonic Acidemia", GeneReviews®, Seattle (WA): University of Washington, Seattle, PMID   20301409 , retrieved 2024-03-09
  18. ↑ Shchelochkov, Oleg A.; Carrillo, Nuria; Venditti, Charles (1993), Adam, Margaret P.; Feldman, Jerry; Mirzaa, Ghayda M.; Pagon, Roberta A. (eds.), "Propionic Acidemia", GeneReviews®, Seattle (WA): University of Washington, Seattle, PMID   22593918 , retrieved 2024-03-09
  19. ↑ Qaisrani, Shafqat Nawaz; Ahmed, Ibrar; Azam, Faheem; Bibi, Fehmida; Saima; Pasha, Talat Naseer; Azam, Farooq (2018-07-01). "Threonine in broiler diets: an updated review". Annals of Animal Science. 18 (3): 659–674. doi: 10.2478/aoas-2018-0020 . ISSN   2300-8733.
  20. ↑ Tang, Qi; Peng, Tan; Ning, Ma; Xi, Ma (2021-07-28). "Physiological Functions of Threonine in Animals: Beyond Nutrition Metabolism". Nutrients. 13 (8): 2592. doi: 10.3390/nu13082592 . PMC   8399342 . PMID   34444752.
  21. ↑ Tuberculosis (TB). Accessed April 13, 2025.
  22. ↑ Théze J, Kleidman L, St Girons I. Homoserine kinase from Escherichia coli K-12: properties, inhibition by L-threonine, and regulation of biosynthesis. J Bacteriol. 1974;118(2):577–581. doi:10.1128/jb.118.2.577-581.1974
  23. ↑ Kinsella RJ, Fitzpatrick DA, Creevey CJ, McInerney JO. Fatty acid biosynthesis in Mycobacterium tuberculosis: Lateral gene transfer, adaptive evolution, and gene duplication. Proc Natl Acad Sci U S A. 2003;100(18):10320–10325. doi:10.1073/pnas.1737230100
  24. ↑ "Error". ndb.nal.usda.gov. Archived from the original on 2018-11-16. Retrieved 2013-05-29.
  25. ↑ "SELF Nutrition Data - Food Facts, Information & Calorie Calculator". nutritiondata.self.com. Retrieved 27 March 2018.
  26. ↑ Carter, Herbert E.; West, Harold D. (1940). "dl-Threonine". Organic Syntheses . 20: 101; Collected Volumes, vol. 3, p. 813..
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