Thiol S-methyltransferase: suggested role in detoxication of intestinal hydrogen sulfide

Weisiger, Richard A.; Pinkus, Lawrence M.; Jakoby, William B.

doi:10.1016/0006-2952(80)90029-5

Cited by 141 publications

(66 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The rate of metabolism of H 2 S by cecal tissue, which averaged 21 nmol/min per milligram of protein, was about 8 times that of hepatic tissue. This 8:1 activity ratio contrasts with reported measurements of thiol S-methyltransferase activity, which showed roughly equal activity in colonic mucosa and liver (8).…”

Section: Figurecontrasting

confidence: 99%

“…The reported rate of methylation of H 2 S by colonic mucosa (8), 127 fmol/min per milligram of protein, is only about 1/10,000 the rate of H 2 S oxidation observed in the present study. In contrast to the methylation rate, the oxidation of H 2 S observed in the present study is of the order of magnitude required to metabolize all H 2 S produced in the rat cecum, and hence could protect the cecal mucosa from the injurious potential of this compound.…”

Section: Figurecontrasting

confidence: 82%

“…Such methylation would result in the conversion of H 2 S to CH 3 SH, and then CH 3 SH to dimethylsulfide (CH 3 SCH 3 ), a relatively nontoxic compound. However, the reported rate of methylation of H 2 S by rat colonic mucosa is only about 10 -13 mol/min per milligram of protein (8). This activity appears to be many orders of magnitude less than that required to metabolize H 2 S released in the colon, which we found to occur at a rate of about 10 -7 mol/min in the rat cecum (9).…”

mentioning

confidence: 70%

“…Recent literature assumes that a similar mechanism is used in the detoxification of the lowmolecular-weight thiols H 2 S and CH 3 SH (5)(6)(7)(8). Such methylation would result in the conversion of H 2 S to CH 3 SH, and then CH 3 SH to dimethylsulfide (CH 3 SCH 3 ), a relatively nontoxic compound.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa

Levitt¹,

Furne²,

Springfield³

et al. 1999

J. Clin. Invest.

225

155

View full text Add to dashboard Cite

The colonic bacteria produce large quantities of hydrogen sulfide (H 2 S) and methanethiol (CH 3 SH), highly toxic compounds with LD 50 's for rodents that are on the same order of magnitude as cyanide. Given the very high exposure of the colonic mucosa to H 2 S and CH 3 SH, local tissue damage would be expected if the mucosa did not possess an efficient detoxification mechanism. The possibility that sulfide might be injurious to colonic mucosa was first proposed by Roediger and Nance (1), who postulated that excess sulfide production could play an etiological role in ulcerative colitis.A variety of high-molecular-weight thiols are detoxified in a methylation reaction catalyzed by thiol S-methyltransferase (2-4). Recent literature assumes that a similar mechanism is used in the detoxification of the lowmolecular-weight thiols H 2 S and CH 3 SH (5-8). Such methylation would result in the conversion of H 2 S to CH 3 SH, and then CH 3 SH to dimethylsulfide (CH 3 SCH 3 ), a relatively nontoxic compound. However, the reported rate of methylation of H 2 S by rat colonic mucosa is only about 10 -13 mol/min per milligram of protein (8). This activity appears to be many orders of magnitude less than that required to metabolize H 2 S released in the colon, which we found to occur at a rate of about 10 -7 mol/min in the rat cecum (9).In the process of incubating H 2 S and CH 3 SH with rat cecal mucosa, we observed that both gases disappeared far more rapidly than could be accounted for by reported methylation rates. The present report describes in vitro and in vivo experiments demonstrating that the colonic mucosa possesses a very efficient, but largely unrecognized, system to metabolize H 2 S and CH 3 SH. This system proceeds, not by methylation, but rather by demethylation of CH 3 SH to H 2 S and oxidation of H 2 S primarily to thiosulfate. MethodsTissues. Cecal and hepatic tissues were obtained from male Sprague-Dawley rats (300-400 g) while the animals were under pentobarbital anesthesia. The cecum was first cleansed of luminal debris by rinsing with isotonic saline, and the mucosa was then scraped off using the edge of a glass microscope slide. Tissue samples were maintained on ice until homogenized in an ice-cold buffer solution in a ratio of 1 part tissue to 15 parts buffer (wt/vol). Homogenization was performed with a Duall grinder (Kontes, Vineland, New Jersey, USA) with a Teflon pestle, using 8-10 strokes. Except when noted, studies were carried out using RPMI buffer, which has a pH of 7.4 when equilibrated with 5% CO 2 . This buffer contains a variety of electrolytes, including 0.4 mM sulfate. In addition, some studies were carried out in 0.1 M PBS (pH 7.0) or a buffer system containing 1.15% KCl, 5 mM Tris-HCl (pH 7.8), and 0.475 mM of the methyl donor S-adenosylmethionine, a milieu used in previously published studies (7) designed to assess thiol S-methyltransferase activity.Incubation studies. A 32-µL volume of homogenate or buffer was added to 20-mL polypropylene syringes. (Preliminary studies showed that bo...

show abstract

Section: Figurecontrasting

confidence: 99%

Section: Figurecontrasting

confidence: 82%

mentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa

Levitt¹,

Furne²,

Springfield³

et al. 1999

J. Clin. Invest.

225

155

View full text Add to dashboard Cite

show abstract

“…H 2 S is oxidized in mitochondria to thiosulfate (4,34,72), methylated in the cytosol to methanethiol and dimethylsulfate (69), and sequestered with macromolecules (56). To determine the mechanism by which endogenous H 2 S is degraded, it is useful to examine the molecular fate of H 2 [35] S applied to tissues.…”

Section: General Interdisciplinary View Of the Inactivation Of H 2 Smentioning

confidence: 99%

Endogenous Production of H₂S in the Gastrointestinal Tract: Still in Search of a Physiologic Function

Linden

Levitt

Farrugia

et al. 2010

Antioxidants & Redox Signaling

104

View full text Add to dashboard Cite

Hydrogen sulfide (H 2 S) has long been associated with the gastrointestinal tract, especially the bacteria-derived H 2 S present in flatus. Along with evidence from other organ systems, the finding that gastrointestinal tissues are capable of endogenous production of H 2 S has led to the hypothesis that H 2 S is an endogenous gaseous signaling molecule. In this review, the criteria of gasotransmitters are reexamined, and evidence from the literature regarding H 2 S as a gaseous signaling molecule is discussed. H 2 S is produced enzymatically by gastrointestinal tissues, but evidence is lacking on whether H 2 S production is regulated. H 2 S causes well-defined physiologic effects in gastrointestinal tissues, but evidence for a receptor for H 2 S is lacking. H 2 S is inactivated through enzymatic oxidation, but evidence is lacking on whether manipulating H 2 S oxidation alters endogenous cell signaling. Remaining questions regarding the role of H 2 S as a gaseous signaling molecule in the gastrointestinal tract suggest that H 2 S currently remains a molecule in search of a physiologic function. Antioxid. Redox Signal. 12, 1135-1146.

show abstract

Methanethiol Metabolism and Its Role in the Pathogenesis of Hepatic Encephalopathy in Rats and Dogs

Blom¹,

Chamuleau²,

Rothuizen³

et al. 1990

Hepatology

View full text Add to dashboard Cite

The metabolism of methanethiol was studied in rats. Administration of a noncomatogenic dose of methanethiol through inspired air or injection into the upper colon resulted in an elevation of the concentrations of methanethiol mixed disulfides in serum (protein--S--S--CH3 and X--S--S--CH3, X yet unknown) and in urine (X--S--S--CH3). The concentrations of methanethiol mixed disulfides proved to be a relative measure of exposure to methanethiol. The levels of volatile sulfur compounds methanethiol, dimethylsulfide and dimethyldisulfide in the air expired by rats exposed to a noncomatogenic dose of methanethiol through the colon were also elevated. Rats with acute hepatic encephalopathy caused by liver ischemia also showed elevation of methanethiol mixed disulfide levels on challenge of methanethiol through the colon or inspired air, but to a significantly smaller extent than did the corresponding sham-operated rats. This suggests that the liver is at least partly responsible for formation of methanethiol mixed disulfides. No additional toxic effects were observed in the rats with ischemic livers on methanethiol exposition when compared with normal rats, suggesting that the liver does not play an essential role in methanethiol detoxification. Metabolism of methanethiol by blood to sulfate, for example, might be more important. In rats with acute hepatic encephalopathy caused by liver ischemia and in dogs suffering from hepatic encephalopathy resulting from chronic liver disease, large and significant increases in ammonia levels were measured. However, the mean levels of methanethiol mixed disulfides in rats and dogs with hepatic encephalopathy were not different from the mean normal levels in these animals.(ABSTRACT TRUNCATED AT 250 WORDS)

show abstract

Thiol S-methyltransferase: suggested role in detoxication of intestinal hydrogen sulfide

Cited by 141 publications

References 22 publications

Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa

Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa

Endogenous Production of H₂S in the Gastrointestinal Tract: Still in Search of a Physiologic Function

Methanethiol Metabolism and Its Role in the Pathogenesis of Hepatic Encephalopathy in Rats and Dogs

Contact Info

Product

Resources

About

Thiol S-methyltransferase: suggested role in detoxication of intestinal hydrogen sulfide

Cited by 141 publications

References 22 publications

Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa

Detoxification of hydrogen sulfide and methanethiol in the cecal mucosa

Endogenous Production of H2S in the Gastrointestinal Tract: Still in Search of a Physiologic Function

Methanethiol Metabolism and Its Role in the Pathogenesis of Hepatic Encephalopathy in Rats and Dogs

Contact Info

Product

Resources

About

Endogenous Production of H₂S in the Gastrointestinal Tract: Still in Search of a Physiologic Function