Rates of alcohol dehydrogenase-dependent ethanol metabolism in periportal and pericentral regions of the perfused rat liver.
Infusion of ethanol into hemoglobin-free perfused rat liver caused an increase in NADH fluorescence (366 leads to 450 nm) which was measured with a large-tip (2-mm) light guide placed on the surface of the liver. A linear correlation (r = 0.83) was observed between the increase in NADH fluorescence and rate of ethanol uptake in the concentration range 0.05--2.0 mM. When a micro-light guide (tip diameter 170 micrometer) was placed on periportal or pericentral regions of the liver surface, the maximal fluorescence increase due to ethanol (2 mM) was 31.2 +/- 2.0 and 31.9 +/- 1.7% in periportal and pericentral regions, respectively. The infusion of 4-methylpyrazole (80 microM), an inhibitor of alcohol dehydrogenase, completely abolished the fluorescence increase in both regions, indicating that the changes are entirely attributable to perturbation of cofactor levels due to alcohol dehydrogenase-dependent ethanol metabolism. Using the correlation between the NADH fluorescence increase and rate of ethanol uptake, rates of ethanol metabolism in periportal and pericentral regions were calculated. Values for maximal ethanol uptake were identical in periportal and pericentral regions. Half-maximal ethanol uptake was observed at 0.24 and 0.25 mM ethanol in periportal and pericentral regions, respectively. These results indicate that the rates of alcohol dehydrogenase-dependent ethanol metabolism are similar in periportal and pericentral regions of the liver lobule.
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000378:metabolism*; D000818:Animals; D000431:Ethanol / Q000378:metabolism*; D005260:Female; D005453:Fluorescence; D000077604:Fomepizole; D066298:In Vitro Techniques; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D009243:NAD / Q000378:metabolism; D011720:Pyrazoles / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D011720:Pyrazoles; D009243:NAD; D000431:Ethanol; D000077604:Fomepizole; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase