Chronic ethanol consumption decreases mitochondrial and glycolytic production of ATP in liver.
OBJECTIVE
The synthesis of ATP in the liver of the chronic ethanol consumer is suppressed, particularly if the tissue becomes hypoxic. Moreover, the perivenous region of the liver lobule becomes even more oxygen deficient as a result of ethanol consumption. Synthesis of ATP in the perivenous region of the lobule may be depressed in the chronic ethanol consumer due to decreases in both mitochondrial and glycolytic activities. In this study the effects of hypoxia on hepatic ATP levels derived from synthesis by both oxidative phosphorylation and the glycolytic mechanisms were investigated.


METHODS
Rats were pair-fed liquid diets containing 36% of calories as ethanol or an isocaloric control diet. The contributions of glycolysis and mitochondria to ATP production were assessed employing oligomycin, an inhibitor of oxidative phosphorylation. In order to localize the ethanol-elicited lesion in the glycolytic pathway, the metabolism of [3-(3)H] D-glucose was followed in hepatocytes from ethanol-fed and control animals.


RESULTS
Under both hypoxic and normoxic conditions ATP losses were due to decreases in both glycolytic and mitochondrial ATP production. The rate of production of tritiated water from [3-(3)H] D-glucose was significantly decreased in hepatocytes from ethanol-fed animals, which indicates there is an ethanol-elicited lesion in glycolysis between glucose and glyceraldehyde-3-phosphate.
Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Tracey A
TA
Young
Shannon M
SM
Bailey
Cynthia G
CG
Van Horn
Carol C
CC
Cunningham
D000255:Adenosine Triphosphate / Q000096:biosynthesis*; D000428:Alcohol Drinking / Q000378:metabolism*; D000818:Animals; D001711:Biotransformation; D002492:Central Nervous System Depressants / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D005986:Glyceraldehyde 3-Phosphate / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects*; D022781:Hepatocytes / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008930:Mitochondria, Liver / Q000378:metabolism*; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D014475:Uncoupling Agents / Q000494:pharmacology
D002492:Central Nervous System Depressants; D009840:Oligomycins; D014475:Uncoupling Agents; D005986:Glyceraldehyde 3-Phosphate; D000431:Ethanol; D000255:Adenosine Triphosphate; D005947:Glucose