Homoserine (also called isothreonine) is an α-

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...

with the

chemical formula In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, ...

HO₂CCH(NH₂)CH₂CH₂OH. -Homoserine is not one of the common amino acids encoded by DNA. It differs from the

proteinogenic amino acid Proteinogenic amino acids are amino acids that are incorporated biosynthetically into proteins during translation. The word "proteinogenic" means "protein creating". Throughout known life, there are 22 genetically encoded (proteinogenic) amino aci ...

serine Serine (symbol Ser or S) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated − form under biological conditions), a carboxyl group (which is in the deprotonated − form un ...

by insertion of an additional -CH₂- unit into the backbone. Homoserine, or its

lactone Lactones are cyclic carboxylic esters, containing a 1-oxacycloalkan-2-one structure (), or analogues having unsaturation or heteroatoms replacing one or more carbon atoms of the ring. Lactones are formed by intramolecular esterification of the co ...

form, is the product of a

cyanogen bromide Cyanogen bromide is the inorganic compound with the formula (CN)Br or BrCN. It is a colorless solid that is widely used to modify biopolymers, fragment proteins and peptides (cuts the C-terminus of methionine), and synthesize other compounds. ...

cleavage of a

peptide Peptides (, ) are short chains of amino acids linked by peptide bonds. Long chains of amino acids are called proteins. Chains of fewer than twenty amino acids are called oligopeptides, and include dipeptides, tripeptides, and tetrapeptides. A ...

by degradation of

methionine Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...

. Homoserine is an intermediate in the

biosynthesis 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 to form macromolecules. ...

of three

essential amino acid An essential amino acid, or indispensable amino acid, is an amino acid that cannot be synthesized from scratch by the organism fast enough to supply its demand, and must therefore come from the diet. Of the 21 amino acids common to all life form ...

threonine Threonine (symbol Thr or T) is an amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), a carboxyl group (which is in the deprotonated −COO� ...

(an

isomer In chemistry, isomers are molecules or polyatomic ions with identical molecular formulae – that is, same number of atoms of each element – but distinct arrangements of atoms in space. Isomerism is existence or possibility of isomers. Iso ...

of homoserine), and

isoleucine Isoleucine (symbol Ile or I) is an α-amino acid that is used in the biosynthesis of proteins. It contains an α-amino group (which is in the protonated −NH form under biological conditions), an α-carboxylic acid group (which is in the deprot ...

. Its complete biosynthetic pathway includes

glycolysis Glycolysis is the metabolic pathway that converts glucose () into pyruvate (). The free energy released in this process is used to form the high-energy molecules adenosine triphosphate (ATP) and reduced nicotinamide adenine dinucleotide (NADH ...

, the

tricarboxylic acid A tricarboxylic acid is an organic carboxylic acid whose chemical structure contains three carboxyl functional groups (-COOH). The best-known example of a tricarboxylic acid is citric acid. Uses Citric acid cycle Citric acid, a type of tricar ...

(TCA) or

citric acid cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins ...

or the

Krebs cycle The citric acid cycle (CAC)—also known as the Krebs cycle or the TCA cycle (tricarboxylic acid cycle)—is a series of chemical reactions to release stored energy through the oxidation of acetyl-CoA derived from carbohydrates, fats, and protein ...

, and the aspartate metabolic pathway. It forms by two reductions of

aspartic 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 pro ...

via the intermediacy of aspartate semialdehyde.I Specifically, the enzyme

homoserine dehydrogenase In enzymology, a homoserine dehydrogenase () is an enzyme that catalyzes the chemical reaction :L-homoserine + NAD(P)+ \rightleftharpoons L-aspartate 4-semialdehyde + NAD(P)H + H+ The 2 substrates of this enzyme are L-homoserine and NAD+ ( ...

, in association with NADPH, catalyzes a reversible reaction that interconverts L-aspartate-4-semialdehyde to L-homoserine. Then, two other enzymes,

homoserine kinase In enzymology, a homoserine kinase () is an enzyme that catalyzes the chemical reaction :ATP + L-homoserine \rightleftharpoons ADP + O-phospho-L-homoserine Thus, the two substrates of this enzyme are ATP and L-homoserine, whereas its two pr ...

and homoserine o-succinyl transferase use homoserine as a substrate and produce phosphohomoserine and o-succinyl homoserine respectively.

Applications

Commercially, homoserine can serve as precursor to the synthesis of

isobutanol Isobutanol (IUPAC nomenclature: 2-methylpropan-1-ol) is an organic compound with the formula (CH3)2CHCH2OH (sometimes represented as ''i''-BuOH). This colorless, flammable liquid with a characteristic smell is mainly used as a solvent either dire ...

and

1,4-butanediol 1,4-Butanediol, colloquially known as BD or BDO, is a primary alcohol, and an organic compound, with the formula HOCH2CH2CH2CH2OH. It is a colorless viscous liquid. It is one of four stable isomers of butanediol. Synthesis In industrial sy ...

. Purified homoserine is used in enzyme structural studies. Also, homoserine has played important roles in studies to elucidate peptide synthesis and synthesis of

proteoglycan Proteoglycans are proteins that are heavily glycosylated. The basic proteoglycan unit consists of a "core protein" with one or more covalently attached glycosaminoglycan (GAG) chain(s). The point of attachment is a serine (Ser) residue to whic ...

glycopeptides. Bacterial cell lines can make copious amounts of this amino acid.

Biosynthesis

Homoserine is produced from aspartate via aspartate-4-semialdehyde, which is produced from β-phosphoaspartate. By the action of

s, the semialdehyde is converted to homoserine. Homoserine biosyntheses

L-Homoserine is substrate for

, yielding phosphohomoserine (homoserine-phosphate), which is converted to by

threonine synthase The enzyme threonine synthase (EC 4.2.3.1) catalyzes the chemical reaction :''O''-phospho-L-homoserine + H2O \rightleftharpoons L-threonine + phosphate This enzyme belongs to the family of lyases, specifically those carbon-oxygen lyases acting ...

to yield L-threonine. Homoserine is converted to o-succinyl homoserine by homoserine o-succinyl transferase, a precursor to L-methionine. Homoserine allosterically inhibits aspartate kinase and

glutamate dehydrogenase Glutamate dehydrogenase (GLDH, GDH) is an enzyme observed in both prokaryotes and eukaryotic mitochondria. The aforementioned reaction also yields ammonia, which in eukaryotes is canonically processed as a substrate in the urea cycle. Typical ...

. Glutamate dehydrogenase reversibly converts glutamate to α-ketoglutarate and α-ketoglutarate coverts to oxaloacetate through the citric cycle. Threonine acts as another allosteric inhibitor of aspartate kinase and homoserine dehydrogenase, but it is a competitive inhibitor of homoserine kinase.

References

Amino acids Non-proteinogenic amino acids {{biochem-stub