Activities and electrophoretic profiles of alcohol dehydrogenase and aldehyde dehydrogenase in human liver tissues
Koyata, H.; Inoue, K.; Sasaki, H.
Arukoru Kenkyu to Yakubutsu Izon 20(4): 394-409
1985
ISSN/ISBN: 0389-4118 PMID: 3914259 Document Number: 251261
In order to elucidate ethanol metabolism in liver diseases and the characteristic of alcoholic liver injury, activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were studied using liver homogenates in 80 cases of alcoholic and non-alcoholic liver diseases. Assays of the enyzme activities were performed using liver specimens obtained by needle or wedge biopsy. Both alcoholic and non-alcoholic liver diseases were classified according to histological diagnosis. From the result of kinetic study of ADH using normal liver specimen, it was revealed that the apparent Km value of ADH for aceta ldehyde was 0.39 .+-. 0.12 mM. The kinetic study on ALDH revealed the presence of two types of the enzyme with different Michaelis constants; one apparent Km value was 17.5 .+-. 0.3 .mu.M and the other was 1.25 .+-. 0.24 mM. Acetaldehyde produced by ethanol ingestion is considered to be oxidized mostly by low Km ALDH. The assay for both low Km ALDH and total ALDH activities was performed with two different concentrations of acetaldehyde as the substrate. The activity of ADH was decreased by 49%, 34%, 42% and 33% in acute viral hepatitis, chronic active hepatitis, non-alcoholic cirrhosis and alcoholic liver diseases, respectively. The activity of low Km ALDH decreased significantly only in chronic active hepatitis. The reduction of this enzyme activity was also found in the cases of alcoholic liver diseases with marked damage of parenchymal cells. Therefore the reduction of these two enzyme activities was considered to be related to the histological features reflecting the liver cell damage irrespective of history of chronic ethanol consumption. No significant differences in high Km ALDH and total ALDH activities were observed among liver diseases. There was no significant correlation between ADH activity and high Km ALDH activity in each group. On the other hand, when the correlation between ADH activity and low Km ALDH activity was studied, positive correlation was found only in alcoholic liver diseases. Furthermore, less frequent appearance of ALDH type I isozyme deficiency is regarded as characteristic of alcoholic liver diseases.