Non-oxidative metabolism of ethanol by rat pancreatic acini.
BACKGROUND
The pathogenesis of alcoholic pancreatitis may involve the metabolism of ethanol (via oxidative and non-oxidative pathways) within the pancreas. The aims of this study were to determine the rate of non-oxidative metabolism in isolated rat pancreatic acini and to compare this to the rate of ethanol oxidation.


METHODS
Pancreatic acini were isolated from male Sprague-Dawley rats and incubated with (14)C-ethanol. Radiolabelled fatty acid ethyl esters (non-oxidative metabolites) were isolated from lipid extracts by thin-layer chromatography. Radiolabelled acetate (oxidative metabolite) was isolated from the incubation medium by ion-exchange chromatography.


RESULTS
Non-oxidative metabolism by isolated pancreatic acini was demonstrated. At 50 and 100 mmol/l ethanol, fatty acid ethyl ester concentrations were 49.6 +/- 13.3 and 199 +/- 93 micromol/l, respectively. These levels have previously been shown to result in tissue injury. Non-oxidative metabolism was increased 9-fold by addition of oleic acid and inhibited by the lipase inhibitor, tetrahydrolipstatin, by 91.05 +/- 1.99%. The rate of oxidative metabolism was 21-fold higher than that of non-oxidative metabolism.


CONCLUSIONS
Intact pancreatic cells metabolize ethanol by the non-oxidative pathway, generating fatty acid ethyl esters at a rate sufficient to cause pancreatic damage. Oxidative metabolism of ethanol occurs at a much higher rate and may also play a role in pancreatitis.
Haber
Paul S
PS
Pancreatic Research Group, University of New South Wales, Sydney, Australia.
Apte
Minoti V
MV
Moran
Corey
C
Applegate
Tanya L
TL
Pirola
Romano C
RC
Korsten
Mark A
MA
McCaughan
Geoffrey W
GW
Wilson
Jeremy S
JS
D000818:Animals; D002470:Cell Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D007783:Lactones / Q000494:pharmacology; D008049:Lipase / Q000037:antagonists & inhibitors; D008297:Male; D000077403:Orlistat; D010179:Pancreas / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D007783:Lactones; D000431:Ethanol; D000077403:Orlistat; D008049:Lipase