Effect of alcohol on the heart and cardiac metabolism

In this report the disturbances in biochemistry of the heart muscle exposed to alcohol are delineated. All elements of cellular substructures are affected. In plasma membranes, (Na+ + K+)-activated ATPase (EC 3.6.1.3) is inhibited. Mitochondrial damage consists in diminished respiratory function and calcium uptake and binding. High-energy phosphates remain intact. Alcohol also affects the malate-aspartate shuttle. Acetaldehyde, a metabolite of ethanol, has a direct effect on myocardial protein synthesis through microsomal inhibition; however, the development of cardiac hypertrophy is not affected. Malfunction of sarcoplasmic reticulum is evidenced by disturbances in calcium binding and uptake. Effects of ethanol on the contractile machinery are deficiencies in the turnover rate of chemical into mechanical energy (diminished Vmax), and in the number of cross-bridges formed (P0). It increases stiffness of series elastic elements. There is diminished fatty acid oxidation with increased esterification. The involvement of CoA synthetase (EC 6.2.1.1), palmityl-carnitine transferase (EC 2.3.1.7), and pyruvate dehydrogenase complex in disturbed fatty acid oxidation is not certain. The role of catalase in myocardial ethanol oxidation was examined. Ethanol activates myocardial catalase-H2O2 complex (EC 1.11.1.6). The biochemical basis of fetal alcohol syndrome is low hepatic alcohol dehydrogenase (EC 1.1.1.1) activity during fetal life.     

Ethanol metabolism by the rat heart and alcohol dehydrogenase activity.

Rat hearts perfused with oxygenated buffer containing [1-14C]ethanol metabolized small amounts of the ethanol to carbon dioxide. Very sensitive techniques are required to separate the resulting 14CO2 from the ethanol. This metabolism is not inhibited by levels of pyrazole which markedly inhibit NAD dependent liver alcohol dehydrogenase (EC 1.1.1.1). In vitro studies suggest that NADP functions as a cofactor for the rat heart alcohol dehydrogenase activity of crude heart homogenates. The kinetics parameters, the specific activity, and the pH dependence of the enzyme activity measured in these experiments suggest that it may have a minor role in ethanol metabolism by the rat.     

Occurrence of coronary heart diseases and hypertension among wine and concentrating alcohol consumers

There was a significant difference in occurrence of coronary hearth disease and arterial hypertension occurrence in the sample of 16,345 patients living in northeast part of Slovak republic near Polish frontier versus to the viticulture regions of Nove Zamky, Sturovo in favour of villages in Bardejov region. Another difference was that 80 years and older respondents live significantly more frequently in south Slovakian viticulture villages.     

Effect of alcohol on perceived exertion in relation to heart rate and blood lactate

The purpose of the study was to determine whether the perception of exertion is affected by alcohol during physical performance and whether altered self-rating of exertion is the result of an altered perception per se or of an altered physical capacity to perform work. Ten healthy men participated. Each subject was his own control and received an alcohol dose corresponding to 1 g.kg-1 body mass in 40% solution in the experimental session. The exercise test was performed on a cycle ergometer with an initial intensity of 50 W which was increased stepwise by 50 W at 4-min intervals up to near-maximal. The rating of perceived exertion (RPE) did not differ between alcohol and control sessions. Alcohol induced a significant increase in heart rate during exercise at 50 W (delta x = 8 beats.min-1) and at 100 W (delta x = 10 beats.min-1), while the change at higher intensities was insignificant. The systolic blood pressure and the blood lactate concentration were not significantly changed by alcohol. It is concluded that a moderate dose of alcohol does not alter RPE during physical exercise either per se or secondarily to an altered physical capacity to perform work.     

The level of free radical oxidation products in heart and blood plasma in diabetes mellitus combined with chronic alcohol intoxication

The level of glycemia, contents of free radical oxidation products (thiobarbituric acid reactive substances, oxidatively modified proteins) have been investigated in blood plasma and heart of rats with diabetes mellitus subjected to chronic alcohol intoxication. Preexisting diabetes mellitus had no influence on the effect of chronic alcohol consumption on the blood plasma levels of oxidatively modified proteins, thiobarbituric acid reactive substances and glucose. However, the contents of thiobarbituric acid reactive substances and products of oxidative modification of proteins were significantly higher in hearts of diabetic rats with chronic alcohol intoxication than in diabetic rats without alcohol intoxication or in rats subjected to chronic alcohol treatment. The alcohol-induced hyperactivation of free radical processes found in the heart may have additional damaging effect.     

The equilibrium between vitamin A alcohol and aldehyde in the presence of alcohol dehydrogenase

Vitamin A is reversibly dehydrogenated to vitamin A aldehyde (retinene) in isolated retinal rods and in liver extracts containing alcohol dehydrogenase and coenzyme 1.The reaction is probably involved in the utilization of vitamin A for the regeneration of bleached visual purple.The equilibrium constant k_H of the dehydrogenation is 3.3 × 10^?9, about 300 times more favorable to the aldehyde than k_H for ethyl alcohol.     

Change in alcohol consumption and risk of death from all causes and from ischaemic heart disease.

OBJECTIVE--To examine the association between alcohol consumption and mortality from all causes and from ischaemic heart disease with a focus on differentiating between long term abstainers and more recent non-drinkers. DESIGN--Cohort study of changes in alcohol consumption from 1965 to 1974 and mortality from all causes and ischaemic heart disease during 1974-84. SETTING--Population based study of adult residents of Alameda County, California. SUBJECTS--2225 women and 1845 men aged 35 and over in 1965. MAIN OUTCOME MEASURES--Alcohol consumption in 1964 and 1974 and mortality from all causes and from ischaemic heart disease during 1974-84. RESULTS--There was a significantly higher risk of death from all causes and from ischaemic heart disease in women who gave up drinking between 1965 and 1974 than in women who continued to drink (relative risk 1.72, 95% confidence interval 1.11 to 2.66, and 2.75, 1.44 to 5.23, for all causes and ischaemic heart disease respectively). A significant increase in risk was not seen in men who gave up drinking (1.32, 0.87 to 2.01, and 0.95, 0.41 to 2.20, respectively). Among men, long term abstainers compared with drinkers were at increased risk of death from all causes and from ischaemic heart disease, though the associations were not significant (1.40, 0.98 to 2.00, and 1.40, 0.76 to 2.58, for all causes and ischaemic heart disease respectively). CONCLUSION--Some of the increased risk of death from all causes and from ischaemic heart disease associated with not drinking in women seems to be accounted for by higher risks among those who gave up drinking. Men who are long term abstainers may also be at an increased risk of death. The heterogeneity of the non-drinking group should be considered when comparisons are made with drinkers.     

Quinone-dependent alcohol dehydrogenases and fad-dependent alcohol oxidases

This review considers quinone-dependent alcohol dehydrogenases and FAD-dependent alcohol oxidases, enzymes that are present in numerous methylotrophic eu- and prokaryotes and significantly differ in their primary and quaternary structure. The cofactors of the enzymes are bound to the protein polypeptide chain through ionic and hydrophobic interactions. Microorganisms containing these enzymes are described. Methods for purification of the enzymes, their physicochemical properties, and spatial structures are considered. The supposed mechanism of action and practical application of these enzymes as well as their producers are discussed.     

Characteristics of alcohol/polyol dehydrogenases. The zinc-containing long-chain alcohol dehydrogenases

Sixteen characterized alcohol dehydrogenases and one sorbitol dehydrogenase have been aligned. The proteins represent two formally different enzyme activities (EC 1.1.1.1 and EC 1.1.1.14), three different types of molecule (dimeric alcohol dehydrogenase, tetrameric alcohol dehydrogenase, tetrameric sorbitol dehydrogenase), metalloproteins with different zinc contents (1 or 2 atoms per subunit), and polypeptide chains from different kingdoms and orders (mammals, higher plants, fungus, yeasts). Present comparisons utilizing all 17 forms reveal extensive variations in alcohol dehydrogenase, but with evolutionary changes that are of the same order in different branches and at different times. They emphasize the general importance of particular residues, suggesting related overall functional constraints in the molecules. The comparisons also define a few coincidences between intron positions in the genes and gap positions in the gene products. Only 22 residues are strictly conserved; half of these are Gly, and most of the remaining ones are Pro or acidic residues. No basic residue, no straight-chain hydrophobic residues, no aromatic residues, and essentially no branched-chain or polar neutral residues are invariable. Tentative consensus sequences were calculated, defining 13 additional residues likely to be typical of but not invariant among the alcohol dehydrogenases. These show a predominance of Val, charged residues, and Gly. Combined, the comparisons, which are particularly relevant to the data base for protein engineering, illustrate the requirements for functionally important binding interactions, and the extent of space restrictions in proteins with related overall conformations and functions.     

The involvement of alcohol dehydrogenase and aldehyde dehydrogenase in alcohol/aldehyde metabolism in Drosophila melanogaster

In this study we have examined the roles of alcohol dehydrogenase, aldehyde oxidase, and aldehyde dehydrogenase in the adaptation of Drosophila melanogaster to alcohol environments. Fifteen strains were characterized for genetic variation at the above loci by protein electrophoresis. Levels of in vitro enzyme activity were also determined. The strains examined showed considerable variation in enzyme activity for all three gene-enzyme systems. Each enzyme was also characterized for coenzyme requirements, effect of inhibitors, subcellular location, and tissue specific expression. A subset of the strains was chosen to assess the physiological role of each gene-enzyme system in alcohol and aldehyde metabolism. These strains were characterized for both the ability to utilize alcohols and aldehydes as carbon sources as well as the capacity to detoxify such substrates. The results of the above analyses demonstrate the importance of both alcohol dehydrogenase and aldehyde dehydrogenase in the in vivo metabolism of alcohols and aldehydes.