Sulfur amino acid metabolism (Homo sapiens)
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Description
The main sulfur amino acids are methionine, cysteine, homocysteine and taurine. Of these, the first two are proteinogenic.
This group of reactions contains all processes that 1) break down sulfur amino acids, 2) interconvert between them, and 3) synthesize them from solved sulfide which comes from sulfate assimilation and reduction. Only plants and microorganisms employ all processes. Humans cannot de novo synthesize any sulfur amino acid, nor convert cysteine to methionine (Brosnan & Brosnan, 2006). View original pathway at:Reactome.
This group of reactions contains all processes that 1) break down sulfur amino acids, 2) interconvert between them, and 3) synthesize them from solved sulfide which comes from sulfate assimilation and reduction. Only plants and microorganisms employ all processes. Humans cannot de novo synthesize any sulfur amino acid, nor convert cysteine to methionine (Brosnan & Brosnan, 2006). View original pathway at:Reactome.
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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).
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).
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).
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).