Thiosulfate-sulfur transferase

VHPOs also accept the pseudohalides CN and SCN as alternative substrates, and even oxidise cyanide and thiocyanate preferentially to bromide.I l Thiocyanate is generated in vivo by thiosulfate sulfur transferase in the process of cyanide detoxification, and is present in concentrations comparable to that of bromide. Organic thiocyanate compounds have been discovered in marine environments (12 in Figure 4.14, suggesting that their formation is also catalysed by, inter alia, VHPOs. Laboratory experiments have shown... 

Wood and Cooley, 1956). The mitochondrial enzyme rhodanese (thiosulfate sulfur transferase) is... 

HCN is detoxified to thiocyanate (SCN ) by the mitochondrial enzyme rhodanese rhodanese catalyzes the transfer of sulfur from thiosulfate to cyanide to yield thiocyanate, which is relatively nontoxic (Smith 1996). The rate of detoxification of HCN in humans is about 1 pg/kg/min (Schulz 1984) or 4.2 mg/h, which, the author states, is considerably slower than in small rodents. This information resulted from reports of the therapeutic use of sodium nitroprusside to control hypertension. Rhodanese is present in the liver and skeletal muscle of mammalian species as well as in the nasal epithelium. The mitochondria of the nasal and olfactory mucosa of the rat contain nearly seven times as much rhodanese as the liver (Dahl 1989). The enzyme rhodanese is present to a large excess in the human body relative to its substrates (Schulz 1984). This enzyme demonstrates zero-order kinetics, and the limiting factor in the detoxification of HCN is thiosulphate. However, other sulfur-containing substrates, such as cystine and cysteine, can also serve as sulfur donors. Other enzymes, such as 3-mercapto-pyruvate sulfur transferase, can convert... 

The metabolism of cyanide has been studied in animals. The proposed metabolic pathways shown in Figure 2-3 are (1) the major pathway, conversion to thiocyanate by either rhodanese or 3-mercapto-pyruvate sulfur transferase (2) conversion to 2-aminothiazoline-4-carboxylic acid (Wood and Cooley 1956) (3) incorporation into a 1-carbon metabolic pool (Boxer and Richards 1952) or (4) combining with hydroxocobalamin to form cyanocobalamin (vitamin B12) (Ansell and Lewis 1970). Thiocyanate has been shown to account for 60-80% of an administered cyanide dose (Blakley and Coop 1949 Wood and Cooley 1956) while 2-aminothiazoline-4-carboxylic acid accounts for about 15% of the dose (Wood and Cooley 1956). The conversion of cyanide to thiocyanate was first demonstrated in 1894. Conversion of cyanide to thiocyanate is enhanced when cyanide poisoning is treated by intravenous administration of a sulfur donor (Smith 1996 Way 1984). The sulfur donor must have a sulfane sulfur, a sulfur bonded to another sulfur (e.g., sodium thiosulfate). During conversion by rhodanese, a sulfur atom is transferred from the donor to the enzyme, forming a persulfide intermediate. The persulfide sulfur is then transferred... 

It now seems probable that cleavage of thiosulfate in T. thioparus (and Thiobacillus denitrificans) depends not on a reductase as originally perceived by Peck (1960) but on a sulfur transferase of the rhodanese type (Peck 1968). Rhodanese is usually detected by its ability to transfer the sulfane-sulfur of thiosulfate to the nonphysiologic acceptor cyanide, producing thiocyanate and liberating sulfite ... 

This reaction is catalyzed by rhodanase enzyme, also called mitochondrial sulfur transferase. Although not found in the blood, this enzyme does occur abundantly in liver and kidney tissue. Because of this reaction, thiosulfate can be administered as an antidote for cyanide poisoning. 

The toxicity of HCN is linked to the inhibition of cytochrome(a), an enzyme containing 2 Fe(H) and 2 Cu(I) ions. As sulfur transferase transforms the cyanide anion into the harmless thiocyanate ion, the problem is how to provide the cell with enough sulfur. This is, in fact, the basis of part of the treatment of HCN poisoning (consisting of an injection of. sodium thiosulfate). 

Sulfur donors for conversion of cyanide to thiocyanate by rhodanese or other sulfur transferases, that is, a source of sulfur. For moderate poisoning, sodium thiosulfate is the usual choice. 

I. Pharmacology. Sodium thiosulfate is a sulfur donor that promotes the conversion of cyanide to less toxic thiocyanate by the sulfur transferase enzyme rho-danese. Unlike nitrites, thiosulfate is essentially nontoxic and may be given empirically in suspected cyanide poisoning. 

Szczepkowski and Wood showed thiocystine can function as a substrate for rhodanese (thiosulfate cyanide sulfur transferase, EC 2.-8.1.1). (Table I)... 

The released CN is transformed into SCN" by a hepatic and renal enzyme, rhodanese [43—45], this sulfuryl transferase being discovered in 1933 [46]. The enzymatic reaction proceeds slowly unless sulfur is supplied and is stimulated by thiosulfate, which is therefore a powerful antidote for CN poisoning. Another antidote is vitamin B12, and results indicate that as plasma cyanide increases the vitamin Bj2 level decreases suggesting that the vitamin may be a cofactor of rhodanese. Vitamin Bj2 will be in the aqua (not hydroxo) form at physiological pH [47], and cyanocobalamin formation is believed to be responsible for the antidotal properties [48—50]. Side effects have also been noted, however, in this connection [43, 51], and low plasma B12 levels may complicate treatment. The direct interaction between nitroprusside and vitamin B12 has been examined by NMR and 1 1 and 1 2 adducts have been observed [47],... 

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