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).
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
hydroxylside-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]
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:
In humans the gene for threonine dehydrogenase is an inactive
pseudogene,[10] so threonine is converted to
α-ketobutyrate. The mechanism of the first step is analogous to that catalyzed by
serine dehydratase, and the serine and threonine dehydratase reactions are probably catalyzed by the same enzyme.[11]
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]
^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, retrieved 2024-03-09
^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, retrieved 2024-03-09