In vivo uptake of ethanol and release of acetate in rat liver and GI.
The concentration gradients of ethanol and acetate across liver and GI were determined in overnight starved rats infused with ethanol at a rate (15 mu mol/min/rat) below and a rate (30 mu mol/min/rat) exceeding the rate of ethanol disposal in the animals. Plasma concentrations of ethanol in the systemic circulation reached steady-state levels of approximately 0.6 mM between 30 and 60 min during low rate of infusion; increased steadily from 3.5 mM at 30 min to 6.4 mM at 2 h during high rate of infusion. GI metabolism was determined by concentration differences in aorta and portal vein; hepatic metabolism by differences in hepatic influx and hepatic veins. Hepatic influx was the sum of the concentrations in aorta and portal vein, each multiplied by their fractional contributions to hepatic blood supply. At low rate of infusion, hepatic extraction of ethanol was nearly complete and could be accounted for entirely by the acetate released from liver. The concentrations of ethanol in aorta were greater but not significantly than that in portal vein. At high rate of infusion, hepatic and GI gradients of ethanol remained constant despite changes in circulating concentrations of ethanol. The concentration gradients of ethanol and acetate across liver, though different in signs, were identical in magnitude. GI gradient indicating uptake of ethanol was statistically significant and was about 30% of hepatic gradient. Enzyme activity of alcohol dehydrogenase in stomach was found to be about 10% of that in liver. Our results thus show that acetate generated during ethanol oxidation is completely released from liver in rats, in either conscious or anesthetized state under submaximal or maximal condition of ethanol disposal, and that GI metabolism of circulating ethanol can be as high as one third of the metabolism in liver.
Huang
M T
MT
Laboratory of Metabolism, Chang Gung Medical College, Kwei-san, Tao-yuan, Taiwan.
Huang
C C
CC
Chen
M Y
MY
D000085:Acetates / Q000378:metabolism*; D000426:Alcohol Dehydrogenase / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000737:chemistry; D004064:Digestive System / Q000378:metabolism*; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000201:enzymology; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D011169:Portal Vein / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
D000085:Acetates; D000431:Ethanol; D000426:Alcohol Dehydrogenase