Influence of chronic alcohol abuse and liver disease on hepatic aldehyde dehydrogenase activity.
Alcohol metabolism results in the production of acetaldehyde, a compound that is much more toxic than ethanol itself. Hepatic aldehyde dehydrogenase (ALDH) is the main enzymatic system responsible for acetaldehyde clearance from the hepatocyte. The objective of this study was to determine the modifications in ALDH activity due to chronic alcohol abuse and liver disease. ALDH activity was determined in samples of liver tissue from 69 alcoholic and 82 nonalcoholic subjects, with and without liver disease. According to the results of liver pathology examination, alcoholic patients were classified into the following groups: controls, with no liver disease (group 1), noncirrhotic liver disease patients (group 2), and cirrhotics (group 3). Nonalcoholic subjects were categorized, using the same criteria, into groups 4, 5, and 6, respectively. ALDH activity was determined spectrophotometrically at two substrate concentrations: 18 mM for total activity and 180 microM for low Km activity. High Km activity was calculated by subtracting the low Km activity value from that of total ALDH activity. Results obtained in each group were expressed as the mean +/- SD of mU of g of wet weight. There were no significant differences when the total ALDH activity from the alcoholic and the nonalcoholic patients with a similar degree of liver pathology were compared: group 1, 1257 +/- 587 vs. group 4, 1328.1 +/- 546.2 (p: NS); group 2, 919.1 +/- 452.4 vs. group 5, 753.5 +/- 412 (p: NS); and group 3, 430.2 +/- 162.4 vs. group 6, 473.2 +/- 225.3 (p: NS). On the other hand, total ALDH activity was significantly lower in cirrhotics than in controls, both among alcoholics (p < 0.01) and among nondrinkers (p < 0.05). The low Km activity was severely reduced in cirrhotics, both alcoholics and nonalcoholics (p < 0.01). High Km activities in cirrhotic patients were low, compared to controls, both in alcoholics and nonalcoholics, although the difference was nonsignificant. The results of the present study suggests that chronic alcohol abuse does not depress ALDH activity. A reduction in the ALDH activity detected in patients with severe liver disease (cirrhotics) was clearly a consequence of liver damage. This reduction was due mainly to a decrease of the low Km ALDH activity, but a trend to a decrease in the high Km ALDH activity was also detected.
Vidal
F
F
Department of Internal Medicine, Hospital Universitari de Tarragona JOAN XXIII, Facultat de Medicina i Ciències de la Salut (Reus), Universitat Rovira i Virgili, Spain.
Toda
R
R
Gutiérrez
C
C
Broch
M
M
Fernández-Muixí
F
F
Lorenzo
A
A
Richart
C
C
D000328:Adult; D000368:Aged; D000437:Alcoholism / Q000201:enzymology*; D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D005235:Fatty Liver, Alcoholic / Q000201:enzymology; D005260:Female; D006519:Hepatitis, Alcoholic / Q000201:enzymology; D006801:Humans; D008099:Liver / Q000201:enzymology; D008104:Liver Cirrhosis, Alcoholic / Q000201:enzymology; D008107:Liver Diseases / Q000201:enzymology*; D008108:Liver Diseases, Alcoholic / Q000201:enzymology; D008297:Male; D008875:Middle Aged
D000444:Aldehyde Dehydrogenase