Mucosal protection against sulphide: importance of the enzyme rhodanese.
BACKGROUND
Hydrogen sulphide (H(2)S) is a potent toxin normally present in the colonic lumen which may play a role in ulcerative colitis (UC). Two enzymes, thiol methyltransferase (TMT) and rhodanese (RHOD), are thought to be responsible for sulphide removal but supportive evidence is lacking.


OBJECTIVE
To determine the distribution of TMT and RHOD in different sites throughout the gastrointestinal tract and their efficacy as detoxifiers of H(2)S.


METHODS
Enzyme activities were measured in normal tissue resected from patients with cancer. TMT and RHOD activities were determined using their conventional substrates, 2-mercaptoethanol and sodium thiosulphate, respectively. For measurement of H(2)S metabolism, sodium sulphide was used in the absence of dithiothreitol. Thiopurine methyltransferase (TPMT), which in common with TMT methylates sulphydryl groups but is not thought to act on H(2)S, was also examined.


RESULTS
TMT, RHOD, and TPMT activities using their conventional substrates were found throughout the gastrointestinal tract with highest activity in the colonic mucosa. When H(2)S was given as substrate, no reaction product was found with TMT or TPMT but RHOD was extremely active (Km 8.8 mM, Vmax 14.6 nmol/mg/min). Incubation of colonic homogenates with a specific RHOD antibody prevented the metabolism of H(2)S, indicating that RHOD is responsible for detoxifying H(2)S. A purified preparation of RHOD also detoxified H(2)S.


CONCLUSIONS
RHOD, located in the submucosa and crypts of the colon, is the principal enzyme involved in H(2)S detoxication. TMT does not participate in the detoxication of H(2)S.
Picton
R
R
Division of Medical Sciences, Department of Medicine, University of Birmingham, Birmingham B15 2TH, UK.
Eggo
M C
MC
Merrill
G A
GA
Langman
M J S
MJ
Singh
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000209:etiology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006862:Hydrogen Sulfide / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000201:enzymology; D007422:Intestines / Q000201:enzymology*; D008297:Male; D008780:Methyltransferases / Q000378:metabolism*; D008875:Middle Aged; D013861:Thiocyanates / Q000097:blood; D013884:Thiosulfate Sulfurtransferase / Q000378:metabolism*
D013861:Thiocyanates; D008780:Methyltransferases; C022742:thiol S-methyltransferase; D013884:Thiosulfate Sulfurtransferase; C031760:thiocyanate; D006862:Hydrogen Sulfide