Transulfuration

Thiocyanate metabolites resulting from the transulfuration process are about 120 times less toxic than the parent cyanide compound. 

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

As shown in Figure 10.9, the methyl donor is S-adenosyl methionine, which is demethylated to S-adenosyl homocysteine. After removal of the adenosyl group, homocysteine may undergo one of two metabolic fates remethylation to methionine or condensation with serine to form cystathionine, foUowed by cleavage to yield cysteine - the transulfuration pathway (Section 9.5.5). Cystathionine synthetase has a relatively low Tni compared with normal intra-ceUular concentrations of homocysteine. It functions at a relatively constant rate, and under normal conditions, most homocysteine wUl be remethylated to methionine. 

The other reactions involved in the catabolism of amino acids are decarboxylation, transulfuration, desulfuration, dehydration etc. The decarboxylation process is important since the products of decarboxylation reactions give rise to physiologically active amines. 

The biodistribution of CN to various systemic tissues will determine the relative proportions of CN present at detoxification and target tissue or cellular sites. For example, inhaled or percutaneously absorbed CN enters the systemic circulation and only a small proportion of the absorbed dose will be available for first-pass detoxification, particularly in the liver. In contrast, a high proportion of a p.o. dose will pass through the liver and be available for first-pass detoxification. However, hepatic detoxification processes may be complex, since it has been demonstrated that dietary variations that cause alterations in hepatic sulfurtransferase activity do not correlate with CN toxicity (Rutkowski et ah, 1985), and extensive chemical or surgical injury to the liver does not increase the susceptibility of the mouse to CN toxicity (Rutkowski et ah, 1986). The influence of route on toxicity is probably due to the relative effects of plasma transulfuration, sequestration by erythrocytes, intracellular macromolecular binding, and the differential distribution to all tissues with a detoxification capacity. 

The sulfur atom of methionine becomes the sulfur atom of cysteine. The sulfate generated in cysteine catabolism is excreted or used in several biosynthetic or catabolic pathways. The transulfuration and methylation pathways are intimately related. 

Transulfuration. It aids in the transfer of sulfhydryl-group (HS) from the amino acid methionine to another amino acid (serine) to form the amino acid cysteine. 

D. Cavallini, C. De Marco, B. Mondovi and B.G. Mori. Cleavage of cystine by cystathionase and the transulfuration of hypotau-... 

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