Systemic illnesses (diabetes mellitus, sarcoidosis, alcoholism, and porphyrias)
Jacques Corcos, David Ginsberg, Gilles Karsenty in Textbook of the Neurogenic Bladder, 2015
Ethanol is nearly insoluble in fats and oils, although, like water, it can pass through biological membranes. It distributes proportionally from blood into all tissue and fluids relative to their water content. Because of this characteristic, a certain amount of ethanol is excreted directly through the lungs, urine, and sweat. Ethanol is absorbed through the mucous membranes of the digestive tract. The major part of ethanol metabolism to acetaldehyde occurs primarily in the liver. The enzyme alcohol dehydrogenase (ADH) converts ethanol to aldehyde via oxidation in the cell cytosol. Aldehyde is rapidly destroyed by aldehyde dehydrogenase (ALDH) in the cytosol and mitochondria. At high concentrations of ethanol, a second pathway is activated where the smooth endoplasmic reticulum metabolizes ethanol via oxidation. Besides central nervous system adaptation, alcoholics often display an increased rate of blood ethanol clearance, leading to metabolic tolerance and adaptation. There are intracellular changes seen such as induction of ADHs, increased shuttle capacity, increased oxidation of NADH by mitochondria, hypermetabolic state, and increased release of cytokines or prostaglandins, leading to increase oxygen consumption by liver cells. These cellular effects of chronic alcohol consumption may continue several weeks after cessation of drinking. Further, the neurons may require ethanol temporarily to function optimally during this stage. At this point, a person has developed physiological dependence.53
Food Types, Dietary Supplements, and Roles
Chuong Pham-Huy, Bruno Pham Huy in Food and Lifestyle in Health and Disease, 2022
The metabolism of alcohol is essential to human life. Alcohol metabolism takes place mainly in the liver and relies on two major nicotinamide adenine dinucleotide (NAD)-dependent enzymes, alcohol dehydrogenase (ADH), and aldehyde dehydrogenase 2 (ALDH2). Alcohol is first converted into acetaldehyde by ADH and cytochrome p450 2E1 (CYP2E1) via oxidative degradation, and the acetaldehyde is then oxidized to nontoxic acetate by ALDH and the coenzyme NAD or NADP for excretion (49). These two enzymes help break apart the alcohol molecule in order to eliminate it from the body. First, alcohol dehydrogenase (ADH) metabolizes alcohol to acetaldehyde, a highly toxic substance and known carcinogen (50). Acetaldehyde is generally short-lived; it is quickly broken down to a less toxic compound called acetate (CH3COO-) by another enzyme called aldehyde dehydrogenase (ALDH). Acetate then is broken down into carbon dioxide gas (CO2) and water, mainly in tissues other than the liver for easy elimination (49–51).
Alcohol-Induced Hepatotoxicity
Robert G. Meeks, Steadman D. Harrison, Richard J. Bull in Hepatotoxicology, 2020
Only 2–10% of the ethanol absorbed is eliminated through the kidneys and lungs. The rest must be oxidized in the body, principally in the liver, which contains the bulk of the body’s enzymes capable of ethanol oxidation. This relative organ specificity probably explains why ethanol oxidation produces striking metabolic imbalances in the liver. These effects are aggravated by the lack of feedback mechanism to adjust the rate of ethanol oxidation to the metabolic state of the hepatocyte, and the inability of ethanol, unlike other major sources of calories, to be stored or metabolized to a significant degree in peripheral tissues. When ethanol is present, it becomes the preferred fuel for the liver. By displacing up to 90% of all other substrates normally utilized by the liver (Lundquist and co-workers, 1962), ethanol literally takes over the intermediary metabolism of the liver. Ethanol metabolism in the liver results in the production of hydrogen and acetaldehyde (Figure 2). Each of these two products is directly responsible for a variety of metabolic alterations that play a role in the development of liver injury. A link between hepatotoxicity of ethanol and its metabolism could also explain some of the zonal changes in alcoholic liver disease (vide infra).
On the path toward personalized medicine: implications of pharmacogenetic studies of alcohol use disorder medications
Published in Expert Review of Precision Medicine and Drug Development, 2020
Steven J. Nieto, Erica N. Grodin, Lara A. Ray
Several candidates and genome-wide association studies implicate alcohol metabolism genes in risk for AUD. Unfortunately, few studies have examined the influence of these genes on AUD medications. For the most part, alcohol metabolism occurs in the liver wherein several enzymes oxidize alcohol. Alcohol dehydrogenase converts alcohol to acetaldehyde, a potentially toxic metabolite, which is usually rapidly converted to acetic acid by the enzyme acetaldehyde dehydrogenase. Acetaldehyde dehydrogenase (ALDH) occurs in several genetic forms with differential activity. More than one third of individuals with East Asian ancestry inherit the inactive form of ALDH2 [79]. For these individuals, alcohol consumption increases levels of acetaldehyde, causing several negative physiological consequences, such as nausea and vomiting. Thus, inactive ALDH2 may enhance treatment response to drugs that block acetaldehyde metabolism, such as disulfiram. Yoshimura et al. [80] found that alcohol dependent individuals (ICD-9 criteria) with the inactive ALDH2 genotype had higher rates of abstinence from alcohol when treated with disulfiram relative to carriers treated with placebo. Prospective clinical studies with larger sample sizes are needed to examine the influence of alcohol metabolism genes.
D-ribose-L-cysteine exhibits neuroprotective activity through inhibition of oxido-behavioral dysfunctions and modulated activities of neurotransmitters in the cerebellum of Juvenile mice exposed to ethanol
Published in Drug and Chemical Toxicology, 2023
Damilare Adedayo Adekomi, Olamide Janet Olajide, Omowumi Oyeronke Adewale, Akeem Ayodeji Okesina, John Olabode Fatoki, Benedict Abiola Falana, Temidayo Daniel Adeniyi, Adebiyi Aderinola Adegoke, Waliu Adetunji Ojo, Sheriffdeen Oluwabusayo Alabi
Ethanol is known to stimulate oxidative disequilibrium by increasing products of ROS generated by its metabolism, causing the reduction of antioxidants enzymes, and increasing the biomarkers of macromolecules involved in oxidative stress (Ostrowska et al. 2004, Nogales et al. 2014, Lacaille et al. 2015). Alcohol metabolism is primarily carried out by the enzymatic system present in the liver; nevertheless, some other routes can be put to use, example of these include oxidation by the catalase antioxidant enzyme, which functions as a limited-step pathway (Cederbaum 2012). Consequently, augmented systemic oxidative stress and MDA levels, as well as activation of neurodegenerative pathways, have also been previously linked with alcohol abuse (Haorah et al. 2008, Crews and Nixon 2009). Therefore, this increased level of MDA may systemically play a significant role in cellular damage, as well as initiation of several deleterious mechanisms in the brain, leading to several forms of neurological deficits and psychiatric deviations (Zakhari 2006). Previous research has reported that alcohol consumption adversely alters the level of MDA in specific regions of the rodent brain (Smith et al. 2005). The author further reported that only the level of MDA in the cerebellum was significantly affected by alcohol consumption, while the hippocampus and cortex were not affected. Observation from the level of MDA seen in this study agrees with the report of Smith et al. (2005).
Racial, ethnic, and sex differences in heavy drinking and negative alcohol-related consequences in a national sample of NCAA student-athlete drinkers
Published in Journal of American College Health, 2023
Byron L. Zamboanga,, Jennifer E. Merrill,, Janine V. Olthuis,, Jessica L. Martin,, Margeaux Cannon, Juliet T. Jarrell, Alan Meca, Jeffrey J. Milroy, David L. Wyrick,
Despite generally being at lower risk for engagement in past two-week HED and HID, being a female student-athlete was associated with a higher likelihood of experiencing greater levels of past 30-day negative ARC across all racial/ethnic groups. Moreover, and as expected, the association between the number of drinks consumed per week and odds of experiencing higher levels of negative ARC was stronger for females relative to males. In other words, after consuming the same number of drinks, females are more likely to report higher levels of negative ARC than males. Sex differences in alcohol metabolism may explain these findings given that females tend to metabolize alcohol slower than males and thus experience greater levels of intoxication after consuming the same quantity of drinks.17