Characteristics of Helicobacter pylori alcohol dehydrogenase.
BACKGROUND
Helicobacter pylori shows alcohol dehydrogenase activity, which in the presence of ethanol leads to in vitro production of acetaldehyde, a toxic and highly reactive substance. The present study was undertaken to further define H. pylori-related ethanol and acetaldehyde metabolism by characterizing H. pylori alcohol dehydrogenase and by determining whether the organism possesses aldehyde dehydrogenase.


METHODS
Cytosolic alcohol and aldehyde dehydrogenase activities were determined spectrophotometrically. Acetaldehyde produced by cytosol during incubation with ethanol was measured by head space gas chromatography. Isoenzyme pattern was studied using isoelectric focusing.


RESULTS
Significant alcohol dehydrogenase activity was observed at a neutral pH known to occur in gastric mucus. The Km for ethanol oxidation was approximately 100 mmol/L for the two strains tested. Acetaldehyde was formed already from a low ethanol concentration known to prevail in the stomach endogenously. Isoelectric focusing of the enzyme showed activity bands with pI at 7.1-7.3, a pattern different from that of gastric mucosal alcohol dehydrogenase. 4-methylpyrazole inhibited enzyme activity in a competitive manner and suppressed the growth of the organism during culture. Neither Helicobacter strain studied showed aldehyde dehydrogenase activity and can thus not remove acetaldehyde by that pathway.


CONCLUSIONS
Acetaldehyde production by H. pylori from exogenous or endogenous ethanol may be a pathogenetic mechanism behind mucosal injury associated with the organism.
Salmela
K S
KS
Research Unit of Alcohol Diseases, University of Helsinki, Finland.
Roine
R P
RP
Koivisto
T
T
Höök-Nikanne
J
J
Kosunen
T U
TU
Salaspuro
M
M
D000079:Acetaldehyde / Q000378:metabolism; D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D000077604:Fomepizole; D016480:Helicobacter pylori / Q000201:enzymology* / Q000254:growth & development; D007525:Isoelectric Focusing; D011720:Pyrazoles / Q000494:pharmacology; D013194:Staining and Labeling
D011720:Pyrazoles; D000077604:Fomepizole; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D000079:Acetaldehyde