Threonine (symbolThr orT)[2] is anamino acid that is used in thebiosynthesis ofproteins. It contains anα-amino group (which is in the protonated −NH+ 3 form when dissolved in water), acarboxyl group (which is in the deprotonated −COO− form when dissolved in water), and a side chain containing ahydroxyl group, making it apolar, uncharged amino acid. It isessential in humans, meaning the body cannot synthesize it: it must be obtained from the diet. Threonine is synthesized fromaspartate in bacteria such asE. coli.[3] It isencoded by all thecodons starting AC (ACU, ACC, ACA, and ACG).
Threonine sidechains are often hydrogen bonded; the most common small motifs formed are based on interactions withserine:ST turns,ST motifs (often at the beginning ofalpha helices) andST staples (usually at the middle of alpha helices).
The threonine residue is susceptible to numerousposttranslational modifications.[4][5] Thehydroxylside-chain can undergoO-linked glycosylation. In addition, threonine residues undergophosphorylation through the action of a threoninekinase. 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 phosphorylatedligands andmetalions occurring in an organism is important to explain the function of the phosphothreonine in biological processes.[6]
Threonine is one of two proteinogenic amino acids with twostereogenic centers, the other beingisoleucine. Threonine can exist in four possiblestereoisomers with the following configurations: (2S,3R), (2R,3S), (2S,3S) and (2R,3R). However, the nameL-threonine is used for one singlestereoisomer, (2S,3R)-2-amino-3-hydroxybutanoic acid. The stereoisomer (2S,3S), which is rarely present in nature, is calledL-allothreonine.[9]
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 fromaspartic acid via α-aspartyl-semialdehyde andhomoserine. Homoserine undergoesO-phosphorylation; this phosphateester undergoes hydrolysis concomitant with relocation of the OH group.[11] Enzymes involved in a typical biosynthesis of threonine include:
In humans the gene for threonine dehydrogenase is an inactivepseudogene,[12] so threonine is converted toα-ketobutyrate. The mechanism of the first step is analogous to that catalyzed byserine dehydratase, and the serine and threonine dehydratase reactions are probably catalyzed by the same enzyme.[13]
Effects of threonine dietary supplementation have been researched in broilers.[20]
An essential amino acid, threonine is involved in the metabolism of fats, the creation of proteins, the proliferation and differentiation ofembryonic 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 andenergy 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.[21]
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.[22] 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.[23] 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.[24] 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.
^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.
^abManoli, 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,PMID20301409, retrieved2024-03-09
^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,PMID22593918, retrieved2024-03-09
^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
^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
^"Error".ndb.nal.usda.gov. Archived fromthe original on 2018-11-16. Retrieved2013-05-29.
