https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.1840060330

Genetic polymorphism of human liver alcohol and aldehyde dehydrogenases, and their relationship to alcohol metabolism and alcoholism.

Alcohol and withdrawal: From animal research to clinical issues

As various isoenzymes of gastric alcohol dehydrogenase exist and as the effect of sex and age on these enzymes is unknown, this study measured the activity of gastric alcohol dehydrogenase at high and low ethanol concentrations in endoscopic biopsy specimens from a total of 290 patients of various ages and from 10 patients with chronic alcoholism. Gastric alcohol dehydrogenase was also detected by immunohistological tests in biopsy specimens from 40 patients by the use of a polyclonal rabbit antibody against class I alcohol dehydrogenase. A significant correlation was found between the immunohistological reaction assessed by the intensity of the colour reaction in the biopsy specimen and the activity of alcohol dehydrogenase measured at 580 mM ethanol. While alcohol dehydrogenase activity measured at 16 mM ethanol was not significantly affected by age and sex, both factors influenced alcohol dehydrogenase activity measured at 580 mM ethanol. Young women below 50 years of age had significantly lower alcohol dehydrogenase activities in the gastric corpus and antrum when compared with age matched controls (SEM) (6.4 (0.7) v 8.8 (0.6) nmol/min/mg protein; p < 0.001 and 6.0 (1.3) v 9.5 (1.3) nmol/min/mg protein; p < 0.001). Over 50 years of age this sex difference was no longer detectable, as high Km gastric alcohol dehydrogenase activity decreases with age only in men and not in women. In addition, extremely low alcohol dehydrogenase activities have been found in gastric biopsy specimens from young male alcoholics (2.2 (0.5) nmol/min/mg protein), which returned to normal after two to three weeks of abstinence. The activity of alcohol dehydrogenase in the human stomach measured at 580 mM ethanol is decreased in young women, in elderly men, and in the subject with alcoholism. This decrease in alcohol dehydrogenase activity may contribute to the reduced first pass metabolism of ethanol associated with raised ethanol blood concentrations seen in these people.

https://gut.bmj.com/content/gutjnl/34/10/1433.full.pdf

Human gastric alcohol dehydrogenase activity: effect of age, sex, and alcoholism.

Identification of human liver aldehyde dehydrogenases that catalyze the oxidation of aldophosphamide and retinaldehyde.

The extract from an edible vine, Pueraria lobata, has long been used in China to lessen alcohol intoxication. We have previously shown that daidzin, one of the major components from this plant extract, is efficacious in lowering blood alcohol levels and shortens sleep time induced by alcohol ingestion. This study was conducted to test the antidipsotropic effect of daidzin and two other major isoflavonoids, daidzein and puerarin, from Pueraria lobata administered by the oral route. An alcohol-preferring rat model, the selectively-bred P line of rats, was used for the study. All three isoflavonoid compounds were effective in suppressing voluntary alcohol consumption by the P rats. When given orally to P rats at a dose of 100 mg/kg/day, daidzein, daidzin, and puerarin decreased ethanol intake by 75%, 50%, and 40%, respectively. The decrease in alcohol consumption was accompanied by an increase in water intake, so that the total fluid volume consumed daily remained unchanged. The effects of these isoflavonoid compounds on alcohol and water intake were reversible. Suppression of alcohol consumption was evident after 1 day of administration and became maximal after 2 days. Similarly, alcohol preference returned to baseline levels 2 days after discontinuation of the isoflavonoids. Rats receiving the herbal extracts ate the same amounts of food as control animals, and they gained weight normally during the experiments. When administered orally, none of these compounds affected the activities of liver alcohol dehydrogenase and aldehyde dehydrogenase. Therefore, the reversal of alcohol preference produced by these compounds may be mediated via the CNS. Data demonstrate that isoflavonoid compounds extracted from Pueraria lobata is effective in suppressing the appetite for alcohol when taken orally, raising the possibility that other constituents of edible plants may exert similar and more potent actions.

Isoflavonoid Compounds Extracted from Pueraria lobata Suppress Alcohol Preference in a Pharmacogenetic Rat Model of Alcoholism

Subcellular distribution of aldehyde dehydrogenase activities in human liver.

Liver biopsy samples from 45 patients 21 of whom were alcoholic, were used to study the isoenzymes of alcohol dehydrogenase and aldehyde dehydrogenase. The isoenzymes were separated by polyacrylamide gel isoelectric focusing in the pH range 9–11 for alcohol dehydrogenase and 3.5–8.5 for aldehyde dehydrogenase and the gels were specifically stained for enzyme activity. Up to 5 forms of aldehyde dehydrogenase and 8 forms of alcohol dehydrogenase could be separated by these procedures. Although the isoenzyme patterns differed considerably between individuals there were no consistent differences between alcoholics and non-alcoholics, neither was there any correlation with severity of the liver disease. These results do not support the view that an individual's complement of these isoenzymes is an important determining factor in alcoholism.

Kevin Ward

Papers

Subcellular distribution of aldehyde dehydrogenase activities in human liver.

Isoenzymes of human liver alcohol dehydrogenase and aldehyde dehydrogenase in alcoholic and non-alcoholic subjects