Threonine ammonia-lyase

Threonine Ammonia-Lyase (TAL), also known as threonine deaminase or threonine dehydratase, is an enzyme that catalyzes the deamination of threonine to ammonia and 2-ketobutyrate, which is a key step in the metabolism of threonine. This reaction is part of the biosynthetic pathway for the production of isoleucine, an essential amino acid. Threonine ammonia-lyase plays a crucial role in microbial metabolism, plant biology, and also has implications in human health and disease.

Function

Threonine ammonia-lyase is a lyase, specifically an ammonia-lyase, which removes an ammonia group from threonine to produce 2-ketobutyrate and ammonia. 2-Ketobutyrate then undergoes further metabolic processes to eventually form isoleucine. This enzyme is widely present in bacteria, plants, and to a lesser extent in animals. In plants, it is involved in the synthesis of branched-chain amino acids which are essential for plant development and stress responses. In bacteria, it is crucial for the utilization of threonine as a nitrogen source and for the synthesis of isoleucine.

Structure

Threonine ammonia-lyase is a protein that can exist in multiple forms, including homotetramers and homodimers, depending on the species. The enzyme's active site contains a pyridoxal phosphate (PLP) cofactor, which is essential for its catalytic activity. The structure of threonine ammonia-lyase has been elucidated through X-ray crystallography, revealing insights into its mechanism of action and how it binds to substrates and cofactors.

Mechanism

The catalytic mechanism of threonine ammonia-lyase involves the abstraction of a proton from the α-carbon of threonine by the PLP cofactor, leading to the formation of a quinonoid intermediate. This intermediate then undergoes a β-elimination, releasing ammonia and forming 2-ketobutyrate. The enzyme's specificity for threonine and its catalytic efficiency are determined by the precise arrangement of amino acid residues in the active site, which facilitate substrate binding and catalysis.

Clinical Significance

Alterations in the activity of threonine ammonia-lyase have been linked to various human diseases. For example, disorders in amino acid metabolism can result from mutations affecting the enzymes involved in these pathways, including threonine ammonia-lyase. Understanding the function and regulation of this enzyme could lead to new therapeutic strategies for treating metabolic disorders.

Biotechnological Applications

Threonine ammonia-lyase has potential applications in biotechnology, particularly in the production of isoleucine and other branched-chain amino acids. By manipulating the metabolic pathways involving this enzyme, it is possible to enhance the production of these essential amino acids, which have applications in food, feed, and pharmaceutical industries.

See Also

• Amino acid metabolism
• Isoleucine
• Lyase
• Protein structure
• X-ray crystallography

   This article is a biochemistry stub. You can help WikiMD by expanding it!

• 

  Threonine ammonia-lyase

• 

  Active site of threonine ammonia-lyase with PLP

• 

  Mechanism of threonine ammonia-lyase

• 

  Regulation of threonine ammonia-lyase