Thiosulfate—thiol sulfurtransferase

Thiosulfate—thiol sulfurtransferase (TST), also known as rhodanese, is an enzyme that in humans is encoded by the TST gene. This enzyme plays a crucial role in cyanide detoxification by catalyzing the transfer of a sulfur atom from thiosulfate to cyanide, forming thiocyanate, which is less toxic and can be excreted from the body. The activity of TST is found in a wide range of organisms, from bacteria to humans, highlighting its importance in cellular defense mechanisms against cyanide, a potent inhibitor of cellular respiration.

Function

Thiosulfate—thiol sulfurtransferase functions primarily in the mitochondria, where it facilitates the detoxification of cyanide (CN-) by converting it to thiocyanate (SCN-), a much less toxic compound. This reaction is crucial for organisms exposed to cyanide through environmental sources or as a byproduct of metabolic processes. The enzyme utilizes thiosulfate as a sulfur donor and cyanide as a sulfur acceptor in this reaction. Besides its role in cyanide detoxification, TST is also involved in the transfer of sulfur to other thiol compounds, playing a role in the metabolism of sulfur-containing amino acids and the regulation of sulfur balance within the cell.

Structure

The TST enzyme is a homodimer, meaning it consists of two identical subunits. Each subunit contains a catalytic site responsible for the enzyme's activity. The structure of TST has been elucidated through X-ray crystallography, revealing details about its active site and the mechanism of sulfur transfer. The enzyme's structure is crucial for its function, as alterations in the structure due to mutations can significantly affect its activity and, consequently, an organism's ability to detoxify cyanide.

Clinical Significance

Alterations in the TST gene or the enzyme's activity can have significant implications for human health. Reduced activity of TST has been associated with increased susceptibility to cyanide poisoning, which can occur through exposure to smoke from fires, certain industrial chemicals, and foods containing high levels of cyanogenic glycosides, such as cassava. Furthermore, research has suggested a potential role of TST in conditions related to sulfur metabolism, including certain types of cancer and neurodegenerative diseases, although more studies are needed to fully understand these associations.

Genetic

The TST gene is located on chromosome 22 in humans. Variations in this gene can affect the expression and activity of the TST enzyme, potentially impacting an individual's ability to detoxify cyanide. Genetic studies have aimed to identify polymorphisms in the TST gene that may correlate with disease susceptibility or resistance, offering insights into the enzyme's role in human health and disease.

See Also

• Enzyme
• Cyanide poisoning
• Mitochondria
• Sulfur metabolism