Hydrogen sulfide enzymes

Hepatic Effects. Increases in unspecified liver enzyme activities were noted in some of 221 persons exposed by inhalation to hydrogen sulfide (Burnett et al. 1977). No baseline for these effects was available and they were not quantified. 

Female NMRI mice were exposed to 100 ppm of hydrogen sulfide for 2 hours at 4-day intervals excitement was observed (Savolainen et al. 1980). Exposure also resulted in decreased cerebral ribonucleic acid (RNA), decreased orotic acid incorporation into the RNA fraction, and inhibition of cytochrome oxidase. An increase in the glial enzyme marker, 2, 3 -cyclic nucleotide-3 -phosphohydrolase, was seen. Neurochemical effects have been reported in other studies. Decreased leucine uptake and acid proteinase activity in the brain were observed in mice exposed to 100 ppm hydrogen sulfide for 2 hours (Elovaara et al. 1978). Inhibition of brain cytochrome oxidase and a decrease in orotic acid uptake were observed in mice exposed to 100 ppm hydrogen sulfide for up to 4 days (Savolainen et al. 1980). 

Humans may be exposed to hydrogen sulfide both from its endogenous production or from exogenous sources. Most endogenous production apparently results from the metabolism of sulfhydryl-containing amino acids, e.g., cysteine, by bacteria present in both the intestinal tract and the mouth (Beauchamp et al. 1994 Tonzetich and Carpenter 1971) however, it is also produced in the brain and several smooth muscles, e.g., thoraic aorta, by enzymes found in these tissues (Abe and Kimura 1996 Hosoki et al. 1997). 

The mechanism of hydrogen sulfide toxicity is in part similar to that of cyanide. Like cyanide, hydrogen sulfide can inhibit the enzyme cytochrome oxidase resulting in tissue hypoxia. Specific health effects are discussed in greater detail below. 

Hematological Effects. Cyanosis has been reported in a number of reports of accidental exposures to high concentrations of hydrogen sulfide and is believed to result from respiratory distress (Arnold et al. 1985 Tvedt et al. 1991a, 1991b). Decreased activities of the heme-synthesizing enzymes,... 

Alterations in blood heme metabolism have been proposed as a possible indicator of the biological effects of hydrogen sulfide (Jappinen and Tenhunen 1990), but this does not relate to the mechanism of toxicity in humans. The activities of the enzymes of heme synthesis, i.e., delta-aminolevulinic acid synthase (ALA-S) and heme synthase (Haem-S), were examined in 21 cases of acute hydrogen sulfide toxicity in Finnish pulp mill and oil refinery workers. Subjects were exposed to hydrogen sulfide for periods ranging from approximately 1 minute to up to 3.5 hours. Hydrogen sulfide concentrations were considered to be in the range of 20-200 ppm. Several subjects lost consciousness for up to 3 minutes. 

Effect. Potential biomarkers of the subclinical effects of hydrogen sulfide are decreases in the activities of the heme synthesis enzymes, ALA-S and Haem-S (Jappinen and Tenhunen 1990). These effects have nothing to do with the mechanism of toxicity, however. Neurological indices are also used as biomarkers of effect for hydrogen sulfide (Gaitonde et al. 1987 Kilbum 1993 Stine et al. 1976 Tvedt et al. 1991b). 

Haider SS, Hasan M. 1984. Neurochemical changes by inhalation of environmental pollutants sulfur dioxide and hydrogen sulfide Degradation of total lipids, elevation of lipid peroxidation and enzyme activity in discrete regions of the guinea pig brain and spinal cord. Ind Health 22 23-31. 

Khan AA, Schuler MM, Prior MG, et al. 1990. Effects of hydrogen sulfide exposure on lung mitochondrial respiratory chain enzymes in rats. Toxicol Appl Pharmacol 103 482-490. 

Roth SH, Skrajny B, Bennington R, et al. 1997. Neurotoxicity of hydrogen sulfide may result from inhibition of respiratory enzymes. Proc West Pharmacol Soc 40 41-43. 

Hydrogen sulfide is a well known general metabolite produced on sulfate reduction by certain bacteria. Moreover, organic forms of sulfur can give rise to HS , hence H2S in certain bacteria. Thus, cysteine desulfhydrase (EC 4.4.1.1, cystathionine y-lyase) converts L-cysteine to H2S, pyruvate, and NH3. This enzyme shows a requirement for pyridoxal phosphate and the unstable ami-noacrylic acid is an intermediate (Equation 1) in the reaction ... 

A different application of visible microscopy was pioneered by Gomori. In 1941 he showed that alkaline phosphatase could be specifically located by its hydrolysis of soluble phosphate esters (initially glycerophosphate). If calcium ions were present in the medium in which the sections were incubated, insoluble calcium phosphate precipitated as a result of the action of the hydrolase. The site of the precipitate could be visualized if cobalt or lead salts were subsequently added to replace calcium and the sections exposed to hydrogen sulfide. In principle many hydrolases and other enzymes could be studied using the appropriate substrates and precipitants. It was important to ensure that the products of the enzyme reactions did not diffuse from the sites where the enzymes were located. It was also essential that the reagents could reach the enzyme site. 

This glutathione-dependent enzyme catalyzes the reaction of hydrogen sulfide with Fe + to produce sulfite and Fe +. 

This pyridoxal-phosphate-dependent enzyme [EC 4.2.99.9], also known as cystathionine y-synthase, catalyzes the reaction of O-succinyl-L-homoserine with L-cysteine to produce cystathionine and succinate. The enzyme can also use hydrogen sulfide and methanethiol as substrates, producing homocysteine and methionine, respectively. In the absence of a thiol, the enzyme can also catalyze a /3,y-elimination reaction to form 2-oxobu-tanoate, succinate, and ammonia. 

Hydrogen sulfide, H2S, is detoxified by methylation first to methanthiol (CH3SH), which is highly toxic, but is then further methylated to dimethylsulfide (CH3-S-CH3). The thiol products of p-lyase may also be methylated by this enzyme. 

Ligands that can coordinate to an active center in an enzyme and prevent coordination by the substrate will tend to inhibit the action of that enzyme. 1 We have seen that azide can occupy the pocket tailored to fit the carbon dioxide molecule. This prevents the latter from approaching the active site. Furthermore, the infrared evidence indicates that the azide ion actually does bind the zinc atom The asymmetric stretching mode of the azide ion is strongly shifted with respect to the free ion absorption. Thus the zinc is inhibited from acting as a Lewis acid towards water with the formation of a coordinated hydroxide ion. Other inhibitors also bind to the metal atom. As little as 4 x I0-6 M cyanide or hydrogen sulfide inhibits the enzymatic activity by 85%. 

L-/D-cvsteine. Hydrogen sulfide is produced from L-cysteine in a light-independent process that can be inhibited in vivo and in vitro by aminooxy acetic acid, an inhibitor of pyridoxal phosphate-dependent enzymes the hydrogen sulfide emitted in response to L-cysteine is directly derived from die L-cysteine fed ( 2 ). Therefore, hydrogen sulfide appears to be produced from L-cysteine by a pyridoxal phosphate-dependent, L-cysteine specific cysteine desulfhydrase. This conclusion is supported by the finding that in cucurbit... 

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