3-mercaptopyruvate sulfurtransferase (MPST) (MPST)

3-mercaptopyruvate sulfurtransferase (MPST) is a multifunctional enzyme belonging to the sulfurtransferase family, primarily localized in the cytoplasm and mitochondria [1.2.1, 1.3.1]. It plays a pivotal role in the endogenous production of hydrogen sulfide (H2S) and sulfane sulfur, which serve as vital gasotransmitters and signaling molecules in various physiological processes [1.1.1, 1.3.2]. MPST is also critically involved in the detoxification of cyanide and the regulation of cellular redox states through protein persulfidation [1.2.2, 1.2.4]. Dysregulation of this enzyme is associated with several diseases, including the rare metabolic disorder mercaptolactate-cysteine disulfiduria, as well as cardiovascular conditions, neurodegenerative diseases like Alzheimer's, and various cancers [1.2.1, 1.3.2, 1.3.5]. In oncology, MPST often supports tumor bioenergetics and proliferation, making it a target for specific inhibitors like HMPSNE [1.4.1, 1.4.5]. Conversely, MPST-targeted prodrugs such as sulfanegen are being explored to restore H2S levels for neuroprotective and cardioprotective benefits [1.1.3, 1.3.3]. Understanding the context-dependent roles of MPST is essential for developing effective therapeutic interventions that balance its biosynthetic and detoxifying functions [1.3.5].

Other names

3-mercaptopyruvate sulfurtransferaseMSTTST2TUM1Human liver rhodanesetRNA thiouridin modification protein 1Mercaptopyruvate sulfurtransferase

MPST inhibitors, such as HMPSNE, typically block the second step of the enzyme's ping-pong catalytic mechanism, preventing the transfer of a sulfur atom from the persulfurated active-site cysteine to an acceptor molecule [1.4.1, 1.4.4]. Conversely, prodrugs like sulfanegen act as exogenous substrates that are processed by MPST to release therapeutic hydrogen sulfide (H2S) [1.1.3, 1.3.2].