Pyruvic mercapto

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... 

Challenger and Liu (25) found that 3-methiolpropionate or 3-mercapto-pyruvate caused DMS formation by Scopulariopsis brevicaulis. Labarre and Bory (24) observed the conversion of 2-mercaptoacetate to a mixture of HjS and methanethiol by Clostridium oedematicus but mechanisms were not investigated probably a thiol S-methyltransferase catalyzes methanethiol synthesis from sulfide or via an S-methyl derivative of 2-mercaptoacetate. 

A series of 4-amino-6-arylfuranylmethyl-3-mercapto-l,2,4-triazin-5(4//)-ones 339 (R = 4-chloro, 4-nitro, 4-bromo, 2-nitro, 3-nitro, 2-chloro), obtained by refluxing pyruvic acids 340 in ethanol with thiocarbohydrazide, show a good level of antibacterial activity (Figure 23) <2003IJB2649>. 

The enzyme transferring sulphwr from 3-mercapto pyruvate appears to have a similar mechanism, involving a persulphide-like enzymatic intermediate. The possible role of this enzyme in transsulphuration from cysteine has been discussed earlier. 

So far, nothing has been said about mereaptopyruvate as a possible constituent of hiunan urine. Unfortunately, as mercapto-pyruvate is a fairly labile compound our gas chromatographic method was not applicable to the analysis of this compound. We made attempts to stabilize mereaptopyruvate by derivatization of its carbonyl group before analysis by the method just described. Some success was achieved by conversion to the ethoxime, and we observed in fact a small component on gas chromatograms from urine with a retention time identical with that of authentic mereaptopyruvate carried through the modified analytical procedure. However, the identity of this component has not been verified by mass spectrometry and the recovery of mereaptopyruvate is far from acceptable. The only conclusion to be drawn from these experiments is that if mercapto-pyruvate is present in normal human urine, its concentrations are much lower than those of mercaptolactate. 

According to present knowledge transfer of bivalent or sulphane sulphiir from thiosulphate, thiocystine, 3-mercaptopyruvate and some other donors is catalyzed by at least three different enzymes rhodanese /EC 2.8, 1.1/, thiosulphate reductase /no EC number/ and mercapto-pyruvate sulphurtransferase /feC 2.8.1,2/ /for references see Westley, 1973 Koj et al.,1975/ Th mechanism of their action is not uniform rhodanese operates by a double-displacement mechanism /cf. Westley, 1973/ mercaptopyruvate sulphurtransferase by a sequential reaction /Jarabak and Westley,1978/, while the mode of action of thiosulphate reductase is not elucidated. 

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