Ammonium metabolism and protection from urease mediated destruction in Helicobacter pylori infection.
OBJECTIVE
To investigate further the intracellular ammonium metabolism of Helicobacter pylori and the mechanism of its urease mediated destruction.


METHODS
The mechanism of the in vitro destruction of H pylori was investigated by incubating it in buffer solutions, at pH 6.0, containing isocitrate or alpha ketoglutarate in addition to urea concentrations which had previously been shown to destroy H pylori.


RESULTS
The median (range) 5 minute survival of H pylori in 0.2 mol/l citrate buffer (pH 6.0) in the absence of urea was 88% (18-184%) and was similar to its survival in 0.2 mol/l isocitrate buffer in the absence of urea, median 88% (15-274%). In the presence of 50 mmol/l urea the survival of H pylori in the citrate buffer was reduced, 9.9% (0-146%), compared with its survival in isocitrate buffer with the same concentration of urea 37% (0-274%) (p < 0.01). A 72 hour preincubation of the organism with 10 mmol/l alpha ketoglutarate also increased the 5 minute survival of the organism in 0.2 mol/l citrate buffer containing 50 mmol/l urea to 36% (9-145%) compared with its survival in the same buffer but without preincubation with alpha ketoglutarate 0% (0-62%).


CONCLUSIONS
The protection of H pylori from rapid destruction by the supply of compounds used in the intracellular metabolism of the ammonium shows that the urease mediated destruction of H pylori can be explained by intracellular depletion of alpha ketoglutarate as a result of over production of ammonium by uncontrolled urease activity.
Neithercut
W D
WD
Department of Chemical Pathology, Wirral Hospital NHS Trust.
Williams
C
C
Hossack
M S
MS
McColl
K E
KE
D000641:Ammonia / Q000378:metabolism*; D002951:Citrates / Q000494:pharmacology; D019343:Citric Acid; D016481:Helicobacter Infections / Q000378:metabolism*; D016480:Helicobacter pylori / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D007523:Isocitrates / Q000494:pharmacology*; D007656:Ketoglutaric Acids / Q000494:pharmacology*; D014508:Urea / Q000494:pharmacology; D014510:Urease / Q000502:physiology*
D002951:Citrates; D007523:Isocitrates; D007656:Ketoglutaric Acids; D019343:Citric Acid; D000641:Ammonia; D014508:Urea; C034219:isocitric acid; D014510:Urease