Threonine
Threonine is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group, a carboxyl group, 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. It is encoded by all the codons starting AC.
Threonine sidechains are often hydrogen bonded; the most common small motifs formed are based on interactions with serine: ST turns, ST motifs and ST staples.
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 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.It is a precursor of glycine, and can be used as a prodrug to reliably elevate brain glycine levels.
History
Threonine was the last of the 20 common proteinogenic amino acids to be discovered. It was discovered in 1936 by William Cumming Rose, 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| |
| L-Threonine and D-Threonine |
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| L-Allothreonine and D-Allothreonine |
Threonine is one of two proteinogenic amino acids with two chiral centers, the other being isoleucine. Threonine can exist in four possible stereoisomers with the following configurations:,, and. However, the name L-threonine is used for one single diastereomer, -2-amino-3-hydroxybutanoic acid. The second stereoisomer, which is rarely present in nature, is called L-allothreonine. The two stereoisomers - and -2-amino-3-hydroxybutanoic acid are only of minor importance.
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. 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. Enzymes involved in a typical biosynthesis of threonine include:- aspartokinase
- β-aspartate semialdehyde dehydrogenase
- homoserine dehydrogenase
- homoserine kinase
- threonine synthase.
Metabolism
Threonine is metabolized in at least three ways:- In many animals it is converted to pyruvate via threonine dehydrogenase. An intermediate in this pathway can undergo thiolysis with CoA to produce acetyl-CoA and glycine.
- In humans the gene for threonine dehydrogenase is an inactive pseudogene, 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.
- In many organisms it is O-phosphorylated by a kinase preparatory to further metabolism. This is especially important in bacteria as part of the biosynthesis of cobalamin, as the product is converted to -1-aminopropan-2-ol for incorporation into the vitamin's sidechain.