TK2 Human

Thymidine Kinase 2 (TK2) is a mitochondrial enzyme that plays a crucial role in the salvage pathway of nucleotide synthesis. This enzyme is responsible for the phosphorylation of thymidine to thymidine monophosphate (TMP), which is a critical step in the synthesis of mitochondrial DNA (mtDNA). The recombinant form of this enzyme, known as Human Recombinant Thymidine Kinase 2, is produced through genetic engineering techniques and is used in various research and therapeutic applications.

Thymidine Kinase 2 belongs to the DCK/DGK family of enzymes and is a phosphotransferase. It catalyzes the reaction:

$$\text{Thd} + \text{ATP} \rightarrow \text{TMP} + \text{ADP}$$

where Thd is thymidine, ATP is adenosine triphosphate, TMP is thymidine monophosphate, and ADP is adenosine diphosphate . This reaction is essential for the incorporation of thymidine into DNA, making TK2 a key player in DNA synthesis and cell division.

TK2 is encoded by the TK2 gene located on chromosome 16. It is constitutively expressed in most tissues, meaning its expression is relatively constant and not significantly influenced by external factors . The enzyme is particularly important in tissues with high mitochondrial activity, such as muscle and brain tissues.

Mutations in the TK2 gene can lead to a myopathic form of mitochondrial DNA depletion syndrome. This condition is characterized by a significant reduction in mtDNA, leading to muscle weakness and other systemic symptoms . Additionally, oxidative stress can induce S-glutathionylation and proteolytic degradation of TK2, further contributing to mitochondrial dysfunction .

The recombinant form of TK2 is produced using genetic engineering techniques, where the TK2 gene is inserted into a suitable expression system, such as bacteria or yeast, to produce the enzyme in large quantities. This recombinant enzyme is used in various research applications, including:

• Studying mtDNA synthesis: Researchers use recombinant TK2 to investigate the mechanisms of mtDNA replication and repair.
• Drug development: TK2 is a target for developing therapies for mitochondrial disorders. By understanding how TK2 functions and how its activity can be modulated, scientists can develop drugs to treat conditions like mitochondrial DNA depletion syndrome.
• Biochemical assays: Recombinant TK2 is used in assays to measure thymidine phosphorylation activity, which is important for understanding nucleotide metabolism.