MPST transfers sulfur from 3MPYR to HCN to form HSCN

Stable Identifier
R-HSA-9013471
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Cyanide is a potent metabolic poison which binds to and inhibits cytochrome c oxidase (cytochrome a3), resulting in the rapid inhibition of oxidative phosphorylation (Hall & Rumack 1986). As a result, cells can't utilise oxygen, giving rise to central nervous system, cardiovascular and respiratory dysfunction that can result in permanent neurological defects and, in severe cases, death. At body's pH, cyanide exists mainly in the undissociated form hydrogen cyanide (HCN) which can cross cellular and subcellular membranes such as the blood brain barrier and mitochondrial membranes. Although humans aren't typically exposed to toxic levels of cyanide, cyanide intoxication can occur after smoke inhalation, industrial exposure, ingestion of cyanogenic substances and cyanogenic food sources such as cassava. Antidotes for HCN poisoning cases include HCN binders, sulfur donors that convert HCN to the less toxic thiosulfate and competitors for HCN enzymatic binding sites such as NO (Nagahara et al. 1999, Petrikovics et al. 2015).

Two pathways in mammals are able to detoxify cyanide as thiocyanate via transfer of a sulfur atom: thiosulfate sulfurtransferase (TST aka rhodanese) in mitochondria and 3-mercaptopyruvate sulfurtransferase (MPST aka 3MST) in cytosol and mitochondria. MPST mediates the transfer of a sulfur atom from 3-methylpryuvate (3MPYR) to HCN to form the less toxic thiocyanic acid (HSCN) (Himwich & Saunders 1948, Zottola 2009, Moeller et al. 2017). HSCN can be excreted in urine via the kidneys (Hamel 2011). Although the primary role of MPST is not cyanide detoxification, a large body of animal data has demonstrated cyanide is rapidly converted to thiocyanate in vivo when 3MPYR is administered, even in species with low MPST activity (Brenner et al. 2010, Belani et al. 2012).

Literature References
PubMed ID Title Journal Year
28412453 In-vitro mercaptopyruvate sulfurtransferase species comparison in humans and common laboratory animals

Moeller, BM, Crankshaw, DL, Briggs, J, Nagasawa, HT, Patterson, SE

Toxicol. Lett. 2017
19625201 A partial exploration of the potential energy surfaces of SCN and HSCN: implications for the enzyme-mediated detoxification of cyanide

Zottola, MA

J. Mol. Graph. Model. 2009
18872649 Enzymatic conversion of cyanide to thiocyanate

HIMWICH, WA, SAUNDERS, JP

Am. J. Physiol. 1948
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Catalyst Activity
Title
3-mercaptopyruvate sulfurtransferase activity of MPST [mitochondrial matrix]
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Activity
Orthologous Events
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