Ornithine aminotransferase (OAT) is an

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products ...

which is encoded in human by the OAT

gene In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a b ...

located on

chromosome 10 Chromosome 10 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 10 spans about 133 million base pairs (the building material of DNA) and represents between 4 and 4.5 percent of the tot ...

. The OAT involved in the ultimate formation of the

non-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 ...

proline from the

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 a ...

ornithine Ornithine is a non-proteinogenic amino acid that plays a role in the urea cycle. Ornithine is abnormally accumulated in the body in ornithine transcarbamylase deficiency. The radical is ornithyl. Role in urea cycle L-Ornithine is one of the produ ...

. Ornithine

aminotransferase Transaminases or aminotransferases are enzymes that catalyze a transamination reaction between an amino acid and an α-keto acid. They are important in the synthesis of amino acids, which form proteins. Function and mechanism An amino acid co ...

forms the initial intermediate in this process. It catalyzes the reverse reaction as well, and is therefore essential in creating ornithine from the starting substrate proline.

Structure

The OAT gene encodes for a protein that is approximately 46 kDa in size. The OAT protein is expressed primarily in the liver and the kidney but also in the brain and the retina. The OAT protein is localized to the mitochondrion within the cells where it is expressed. The structure of the OAT protein has been resolved using X-ray crystallography and shows similarity to other subgroup 2 aminotransferases such as dialkyglucine decarboxylatse. The OAT protein functions as a

dimer Dimer may refer to: * Dimer (chemistry), a chemical structure formed from two similar sub-units ** Protein dimer, a protein quaternary structure ** d-dimer * Dimer model, an item in statistical mechanics, based on ''domino tiling'' * Julius Dimer ...

and each monomer consists of a large domain, which contributes most to subunit interface, and a C-terminal small domain, and an N-terminal region containing a helix, loop, and three-stranded beta-meander. In the central large domain is a seven-stranded beta-sheet covered by eight helices. The co-factor of the OAT protein (

pyridoxal-5'-phosphate Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent ...

) binds to OAT through a

Schiff base In organic chemistry, a Schiff base (named after Hugo Schiff) is a compound with the general structure ( = alkyl or aryl, but not hydrogen). They can be considered a sub-class of imines, being either secondary ketimines or secondary aldimine ...

at the lysine 292 position situated between two of the seven-stranded beta-sheet. Three amino acids (R 180, E 235, and R413) are thought to be involved in substrate binding at the active site.

Function

Ornithine aminotransferase catalyzes the transfer of the delta-amino group from L-

* L-ornithine + a 2-oxo acid = L-glutamate 5-semialdehyde + an L-amino acid The reaction requires

pyridoxal 5'-phosphate Pyridoxal phosphate (PLP, pyridoxal 5'-phosphate, P5P), the active form of vitamin B6, is a coenzyme in a variety of enzymatic reactions. The International Union of Biochemistry and Molecular Biology has catalogued more than 140 PLP-dependent ac ...

as a co-factor and forms part of the subpathway that synthesizes L- glutamate 5-semialdehyde from L-

Clinical significance

Mutations in the OAT gene can lead to malfunctioning proteins, including both point mutations that abolish catalytic activities, large frame-shift mutations, as well as mutated proteins that are not properly targeted to the mitochondrion where its normal functionality occurs. In the latter, abnormality of mitochondrial import causes ectopic accumulation of the OAT protein in the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

followed by rapid degradation by proteolysis. Deficiency of OAT activities causes

ornithine aminotransferase deficiency Ornithine aminotransferase deficiency (also known as gyrate atrophy of the choroid and retina) is an inborn error of ornithine metabolism, caused by decreased activity of the enzyme ornithine aminotransferase. Biochemically, it can be detected by ...

, also known as gyrate atrophy of choroid and retina. The mechanism of gyrate atrophy of choroid and retina is thought to involve the toxicity of

glyoxylate Glyoxylic acid or oxoacetic acid is an organic compound. Together with acetic acid, glycolic acid, and oxalic acid, glyoxylic acid is one of the C2 carboxylic acids. It is a colourless solid that occurs naturally and is useful industrially. Str ...

References

External links

* * {{Portal bar, Biology, border=no EC 2.6.1 Mitochondrial proteins

Structure

Function

Clinical significance

See also

References

External links