Search results for MPST

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Protein (2 results from a total of 2)

Identifier: R-HSA-9012720
Species: Homo sapiens
Compartment: mitochondrial matrix
Primary external reference: UniProt: MPST: P25325
Identifier: R-HSA-9034913
Species: Homo sapiens
Compartment: mitochondrial matrix
Primary external reference: UniProt: P25325

Reaction (8 results from a total of 8)

Identifier: R-HSA-9034756
Species: Homo sapiens
Compartment: mitochondrial matrix
Hydrogen polysulfides (H2Sn, where n>=2) are also endogenously produced by 3-mercaptopyruvate sulfurtransferase (MPST aka 3MST) directly from 3-mercaptopyruvate (3MPYR) generated by cysteine (aspartate) aminotransferase (GOT2) (Kimura et al. 2013, Kimura et al. 2015, Koike et al. 2017). Where n=2, the H2S2 species is called hydrogen persulfide (aka disulfane). MPST can release either H2S or H2Sn depending on the interaction with thioredoxin. When there is strong interaction with thioredoxin, H2S is released. 3MST receives sulfur from 3MPYR to persulfurate (oxidise) cysteine-248 residue of its reaction centre.

H2S2 is the dominant form produced with H2S3 detected at lower concentrations in cells or tissues. Up to H2S35 may exist (Steudel 2003), but under physiological conditions, when n reaches 8, it forms a crown shape and precipitates. H2Sn activate transient receptor potential ankyrin 1 (TRPA1) channels (Kimura et al. 2013), facilitate translocation of nuclear factor like-2 (NRF2) to the nucleus by modifying its binding partner kelch-like ECH-associated protein 1 (KEAP1) (Koike et al. 2013), regulates the activity of the tumor suppressor phosphatase and tensin homolog (PTEN) (Greiner et al. 2013), and reduces blood pressure by activating protein kinase G1a (Stubbert et al. 2014). Another persulfurated molecule, cysteine persulfide, which may be involved in the regulation of cellular redox homeostasis, is also produced by MPST (Kimura et al. 2017).
Identifier: R-HSA-9013471
Species: Homo sapiens
Compartment: mitochondrial matrix
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).
Identifier: R-HSA-9013533
Species: Homo sapiens
Compartment: mitochondrial matrix
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 are not typically exposed to 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 (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. 3MPYR has been investigated for the potential treatment of HCN poisoning but its half life is very short, being rapidly metabolised when given intravenously (Nagahara & Sawada 2003). Also, it is a metabolite of cysteine metabolism but cysteine is present in low amounts in the brain and heart, limiting the ability of MPST to be effective in acute HCN poisoning. The pro-drug sulfanegen is the hemithioacetal cyclic dimer of 3MPYR and has been demonstrated to be effective against HCN poisoning in animal studies (Brenner et al. 2010, Belani et al. 2012). Sulfanegen provides the sulfur atom for the transsulfuration of HCN by MPST (Belani et al. 2012). HSCN can be excreted in urine via the kidneys (Hamel 2011). In a mass exposure scenario (such as terrorism or industrial accident), a rapidly-acting antidote that can be administered quickly to a large number of people is essential; sulfanegen can be rapidly administered by intramuscular injection (Patterson et al. 2016).
Identifier: R-HSA-9012721
Species: Homo sapiens
Compartment: mitochondrial matrix
Hydrogen sulfide (H2S) produced endogenously has been established as the third gaseous signaling molecule, a smooth muscle relaxant and a neuroprotectant (Kimura 2011a, 2011b). Three enzyme systems produce H2S in the brain, retina and vascular endothelial cells (Shibuya et al. 2009a, 2009b, Mikami et al. 2011). 3-mercaptopyruvate sulphurtransferase (MPST, aka 3MST) in conjunction with cysteine (aspartate) aminotransferase (CAT, aka GOT2) is decribed here. In the second step, 3-mercaptopyruvate sulfurtransferase (MPST aka 3MST) mediates the transfer of a sulfur atom from 3-methylpryuvate (3MPYR) to hydrogensulfite (HSO3-) to form thiosulfate (S2O3(2-)) and pyruvate (PYR) (Yadav et al. 2013).
Identifier: R-HSA-9035227
Species: Homo sapiens
Compartment: mitochondrial matrix
A polysulfur chain may be produced at the catalytic site of CysS248-MPST. H2Sn is released after CysS248-MPST binds mitochondrial thioredoxin (TXN2) (Smeets et al. 2005, Yadav et al. 2013, Holzerova et al. 2016). The length of the sulfur chain released from MPST may vary depending on the availability of thioredoxin (Kimura 2016). When the interaction between MPST and thioredoxin is strong, the shorter form H2S can be released.
Identifier: R-HSA-9035484
Species: Homo sapiens
Compartment: mitochondrial matrix
A polysulfur chain may be produced at the catalytic site of CysS248-MPST. H2Sn is released after CysS248-MPST binds mitochondrial thioredoxin (TXN2) (Smeets et al. 2005, Yadav et al. 2013, Holzerova et al. 2016). The length of the sulfur chain released from MPST may vary depending on the availability of thioredoxin (Kimura 2016). When the interaction between MPST and thioredoxin is strong, the shorter form H2S can be released. Thioredoxin is now in the oxidised, disulfide form (HC-TXN2) and can be reduced by thioredoxin reductase in the presence of NADPH (Smeets et al. 2005, Yadav et al. 2013).
Identifier: R-HSA-9012597
Species: Homo sapiens
Compartment: mitochondrial matrix
Hydrogen sulfide (H2S) produced endogenously has been established as the third gaseous signaling molecule, a smooth muscle relaxant and a neuroprotectant (Kimura 2011a, 2011b). Three human enzyme systems produce H2S in the brain, retina and vascular endothelial cells. 3-mercaptopyruvate sulphurtransferase (MPST, aka 3MST) in conjunction with cysteine (aspartate) aminotransferase (CAT, aka GOT2) is decribed here. The first step is the reversible transamination between L-cysteine (L-Cys) and 2-oxoglutarate (2OG, aka alpha-ketoglutarate) to form 3-methylpyruvate (3MPYR) and glutamate (Glu) catalysed by GOT2. Two forms of human aspartate aminotransferase (GOT) enzymes exist; cytosolic (GOT1) and mitochondrial (GOT2). Both are dimeric proteins requiring pyridoxal phosphate for activity. Human GOT2 (Zhou et al. 1998) possesses the same catalytic activity as its rat counterpart (Ubuka et al. 1978).
Identifier: R-HSA-9013198
Species: Homo sapiens
Compartment: mitochondrial matrix
Cyanide is a potent metabolic poison, a major component of which is binding to and inhibition of 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. 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 (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. TST can act to detoxify HCN by transsulfuration, that is mediating the transfer of a sulfur atom from thiosulfate (S2O3(2-)) to HCN to form the less toxic thiocyanic acid (HSCN) (Himwich & Saunders 1948, Aita et al. 1997, Zottola 2009). HSCN can be excreted in urine via the kidneys (Hamel 2011).

Complex (1 results from a total of 1)

Identifier: R-HSA-9035480
Species: Homo sapiens
Compartment: mitochondrial matrix
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