Rhodanese

Rhodanese, officially known as thiosulfate sulfurtransferase, is a small enzyme that catalyzes the transfer of sulfane sulfur from thiosulfate to various sulfur acceptors, most notably cyanide. In humans it is encoded by the TST gene and is found in mitochondria and, to a lesser extent, the cytosol in many tissues, with highest activity in the liver and kidney.

The enzyme catalyzes the reaction thiosulfate plus cyanide to form sulfite and thiocyanate. The mechanism involves a catalytic cysteine that forms a transient persulfide intermediate; thiosulfate donates a sulfur atom to the enzyme, which then transfers it to cyanide, regenerating the active site. Rhodanese has a two-domain structure, and substrate binding is accompanied by conformational changes that bring the catalytic cysteine and the sulfur acceptor into proximity.

Beyond cyanide detoxification, rhodanese participates in cellular sulfur trafficking and may contribute to metabolism of hydrogen sulfide and the biosynthesis of iron–sulfur clusters in various organisms. It is widespread in mammals, plants, and microbes, and in humans it is expressed broadly, though tissue distribution varies.

Clinically, rhodanese is relevant to cyanide antidote protocols. Thiosulfate serves as a sulfur donor, enabling rhodanese to convert cyanide to thiocyanate, which is then excreted in urine. This enzymatic pathway underpins the use of thiosulfate as part of cyanide poisoning treatment protocols, often in combination with nitrite therapy. Rhodanese remains a useful focus of research in sulfur metabolism and mitochondrial function.