Evidence for a functional genetic polymorphism of the human mercaptopyruvate sulfurtransferase (MPST), a cyanide detoxification enzyme

Mercaptopyruvate sulfurtransferase (MPST) plays a central role in both cysteine degradation and cyanide detoxification. Moreover. deficiency in MPST activity has been suggested to be responsible for a rare inheritable disorder known as mercaptolactate-cysteine disulfiduria (MCDU). To date. 110 Mutation of the human MPST gene has been reported. We developed a screening strategy to search for Mutations in the MPST gene of 50 unrelated French individuals. Two intronic polymorphisms (IVSI - 110C > G and IVS2+39C > T) and a nonsense mutation (Tyr(85) Stop) were identified and their functional consequences were assessed in vivo by measurement of erthrocyte MPST activity and/or in vitro using heterologous expression or transient transfection assay. The nonsense mutation likely leads to tire synthesis of a severely truncated protein without enzymatic activity. a supported by our in vitro data. This work constitutes the first report of the existence of a functional genetic polymorphism affecting MPST and should be of great help to investigate certain disorders such as (c) 2006 Elsevier Ireland Ltd. All rights reserved.