Mercaptopyruvate sulfurtransferase as a defense against cyanide toxication: Molecular properties and mode of detoxification

In cyanide poisoning, metalloproteins and carbonyl groups containing protei ns are the main target molecules of nucleophilic attack by cyanide. To defe nd against this attack, cyanide is metabolized to less toxic thiocyanate vi a transsulfuration. This reaction is catalyzed by rhodanese and mercaptopyr uvate sulfurtransferase (MST). Rhodanese is a well characterized mitochondr ial enzyme. On the other hand, little was known about MST because it was un stable and difficult to purify. We first purified MST to homogeneity and cl oned MST cDNA from rat liver to characterize MST. We also found that MST wa s an evolutionarily related enzyme of rhodanese. MST and rhodanese are wide ly distributed in rat tissues, and the kidney and liver prominently contain these enzymes. Immunohistochemical study revealed that MST is mainly distr ibuted in proximal tubular epithelial cells in the kidney, pericentral hepa tocytes in the liver, the perinuclear area of myocardial cells in the heart , and glial cells in the brain, and immunoelectron microscopical study conc luded that MST was distributed in both cytoplasm and mitochondria, so that MST first detoxifies cyanide in cytoplasm and the cyanide which escapes fro m catalysis due to MST enters mitochondria. MST then detoxifies cyanide aga in in cooperation with rhodanese in mitochondria. Tissues other than the li ver and kidney are more susceptible to cyanide toxicity because they contai n less MST and rhodanese. Even in the same tissue, sensitivity to cyanide t oxicity may differ according to the kind of cell. It is determined by a bal ance between the amount of proteins to be attacked and that of enzymes to d efend.