Enzymes rhodanese-thiosulfate

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

Another permanent cyanide detoxification method involves the intravenous injection of sodimn thiosulfate. The thiosulfate contains a loosely bound sulfur atom that can convert cyanide to thiocyanate by the action of the ubiquitous enzyme rhodanese (thiosulfate-cyanide sulfiutransferase). The much less toxic thiocyanate is excreted via the urine. Rhodanese occius in both the liver and in skeletal muscle and produces a detoxifying action even in the absence of thiosulfate. 

This reaction is catalyzed by the enzyme rhodanese. Thiosulfate and colloidal sulfur are the only compounds so far discovered that react to form thiocyanate. One useful function of this reaction is that it serves to detoxify cyanide, traces of which are also formed endogenously in the metabolism of the mammal. The enzyme rhodanese is widely distributed in animal tissues, the activity in liver being particularly high. Gal, Fung, and Greenberg found that rhodanese activity increases with fetal development up to the time of birth. The rhodanese activity of the mother was not influenced by pregnancy. 

HCN is a systemic poison toxicity is due to inhibition of cytochrome oxidase, which prevents cellular utilization of oxygen. Inhibition of the terminal step of electron transport in cells of the brain results in loss of consciousness, respiratory arrest, and ultimately, death. Stimulation of the chemoreceptors of the carotid and aortic bodies produces a brief period of hyperpnea cardiac irregularities may also occur. The biochemical mechanisms of cyanide action are the same for all mammalian species. HCN is metabolized by the enzyme rhodanese which catalyzes the transfer of sulfur from thiosulfate to cyanide to yield the relatively nontoxic thiocyanate. 

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... 

Cyanide is readily detoxified in animals as all animal tissues contain the thiosulfate sulfurtransferase enzyme rhodanese. Rhodanese readily converts cyanide to the thiocyanate which is excreted in the urine. 

Examples of typical enzyme names are arginase, which acts on arginine, and urease, which acts on urea (Chap. 15). Two atypical common names are pepsin, a digestive tract proteolytic enzyme (EC number 3.4.23.1), and, more exotically, rhodanese (thiosulfate cyanide sulfurtransferase, EC 2.8.1.1), which is in mammalian liver and kidney and catalyzes the removal of cyanide and thiosulfate from the body. In the latter case, it is understandable why the old name has remained in common use. 

Atkinson et al. (1974) reported the antidote action of Kelocyanor [15137-09-4] and enzyme. The bacterial enzyme rhodanese [55073-14-8] mixed with sodium thiosulfate (40 xg and 100 mg/kg) was effective against NaCN in rabbits. Amyl nitrite is a common cyanide antidote. 

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],... 

Rhodanese (thiosulfate cyanide sulfurtransferase EC 2.8.1.1 ) is a mitochondrial enzyme which transfer sulfane sulfur of thiosulfate by a double displacement mechanism involving a sulfur-substituted enzyme ... 

Enzymes as Antidotes. Rhodanese [9026-04-4] given along with thiosulfate to counteract cyanide poisoning in mice (224) was the first enzyme used as an antidote. This combination raised the LD q of potassium cyanide in mice by eightfold (224). 

The two enzyme systems responsible for the transulfuration process are thiosulfate-cyanide sul-furtransferase — also known as rhodanese — and beta-mercaptopyruvate cyanide sulfurtransferase. 

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... 

The thiosulfate reductase/rhodanese/APS reductase system is thus supported by evidence from direct enzyme assay, whole-cell metabolism and energetics, and S-labehng experiments and provides a robust hypothesis to explain thionate oxidation and energy conservation in at least some chemolithotrophs. 

Rhodanese domains I and 2 as an example of a protein with two domains that resemble each other extremely closely. Rhodanese is a liver enzyme that detoxifies cyanide by catalyzing the formation of thiocyanate from thiosulfate and cyanide. (Reprinted by permission of Jane S. Richardson.)... 

The enzyme catalyzing the reaction (4.4) is usually called rhodanese and is thought to occur widely in various organisms. However, as rhodanese requires cyanide of fairly high concentrations (ca. 1 mM) which are not present in normal organisms, the enzyme seems not to occur in Nature. But enzymes occur which have rhodanese activity, e.g., the thiosulfate-cleaving enzyme shows rhodanese activity. Namely, the term rhodanese should not be used as the name of an enzyme, but its use should be limited to the enzymatic activity. 

In Paracoccus vertusus, thiosulfate is oxidized directly to sulfate by the catalysis of an enzyme complex containing several cytochromes c but not cytochrome b (Kelly, 1989). Although sulfite-cytochrome c oxidoreductase occurs in the enzyme complex, the enzyme is thought not to participate in the oxidation of thiosulfate, because the rhodanese activity is not observed with the complex. However, as already indicated, it could be that as the enzyme complex contains a thiosulfatecleaving enzyme strongly bound to both the sulfur-accepting protein and sulfite-cytochrome c oxidoreductase, thiosulfate appears to be oxidized directly to sulfate. 

Thus, the thiosulfate-cleaving enzyme does not show rhodanese activity in the presence of the sulfur-accepting protein (Fukumori et al., 1989). 

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