Alcohol, also known by its chemical name ethanol, is a psychoactive drug commonly found in alcoholic drinks such as beer wine, and spirits. It is metabolized through a metabolic pathway using two enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). Both enzymes help to process the alcohol and eliminate it from the body.
Image Credit: Christian Draghici/Shutterstock.com
Ethanol is converted into acetaldehyde followed by acetic acid before it is broken down into acetyl-CoA. Once ethanol is converted to acetyl-CoA, it can enter the citric acid cycle, which produces energy and releases water and carbon dioxide. Alcohol metabolism differs between adults and pre-natal babies because of the availability of these enzymes, which results in alcohol being processed in the body using different pathways. The liver is the site for alcohol metabolism due to the high concentration of these enzymes present in this organ.
From an evolutionary standpoint, there are certain amino acids in the enzymes that process alcohol, which can be traced back to primitive ancestors. This suggests that alcohol metabolism has been an important part of our evolution. Moreover, catabolic degradation of ethanol is essential to life because all organisms produce alcohol in small quantities using various pathways, mainly through biosynthesis, fatty acid synthesis, and glycerolipid metabolism. Hence, if the body had no way of processing and catabolizing the alcohol, the concentration of alcohol in the body would eventually get to harmful levels.
The concentration of ethanol in tissue is dependent on the amount of water present in the tissue. Thus, ethanol reaches an equilibrium point because it can diffuse from blood to all tissue relative to the water content. Additionally, different blood alcohol concentrations are produced from the same volume of alcohol per unit of body weight. This is due to differences in water and fat content between different body types and gender.
Ethanol conversion in the body
Ethanol is oxidized to acetaldehyde in adults using NAD+, primarily via the hepatic enzyme alcohol dehydrogenase. There are several enzymes within the family of alcohol dehydrogenase that metabolize a range of substrates such as ethanol, retinol, aliphatic alcohols, hydroxysteroids, and lipid peroxidation products. These encoded proteins play a significant role in ethanol catabolism due to their high activity for ethanol oxidation.
In contrast, ethanol is not metabolized within fetuses by the above mechanism observed in adults because alcohol dehydrogenase enzymes are not yet expressed. Expression of these enzymes within the liver only begins after birth and takes several years to develop into levels seen in adults. Thus, fetuses cannot metabolize ethanol at the same rate and require different enzymes. This is observed by detecting high levels of ethanol in the environment surrounding the fetus after clearance by the maternal circulation of alcohol dehydrogenase released from the maternal liver.
CYP2E1 is a particular enzyme in the cytochrome P-450 family where expression and activity of this enzyme has been detected in fetal tissue after the onset of organogenesis. Further release of this enzyme is promoted in the tissue under additional ethanol exposure. The activity of CYP2E1 in fetal tissue is a major contributor to the Microsomal Ethanol Oxidizing System (MEOS) thought to contribute to the toxicity of maternal ethanol consumption.
Converting acetaldehyde to acetyl-CoA
Acetaldehyde is unstable and forms free radicals, which are toxic to the body if not exposed to antioxidants such as ascorbic acid or thiamine. Aldehyde dehydrogenase is the enzyme associated with converting acetaldehyde to acetic acid.
Once the conversion from acetaldehyde to acetic acid occurs, it is then converted into acetyl-CoA by enzymes such as acyl-CoA synthetase and acetyl-CoA synthase to it can enter the citric acid cycle. The citric acid cycle is a series of chemical reactions used in organisms to release energy through the oxidation of acetyl-CoA.
If the body doesn’t convert the free radicals in the body in an efficient way, then it can result in damage to embryonic cells, cause birth defects, and can result in kidney and liver damage in alcoholics. Furthermore, these toxins can cause hang-over effects associated with alcohol consumption.
Sources:
- Collins SE, Kirouac M (2013). "Alcohol Consumption". Encyclopedia of Behavioral Medicine: 61–65.
- Nava-Ocampo, Alejandro A.; Velázquez-Armenta, Yadira; Brien, James F.; Koren, Gideon (June 2004). "Elimination kinetics of ethanol in pregnant women". Reproductive Toxicology. 18 (4): 613–617.
- Brzezinski, Monica R.; Boutelet-Bochan, Helene; Person, Richard E.; Fantel, Alan G.; Juchau, Mont R. (1 June 1999). "Catalytic Activity and Quantitation of Cytochrome P-450 2E1 in Prenatal Human Brain". Journal of Pharmacology and Experimental Therapeutics. 289 (3): 1648–1653.
- Lieber, Charles S. (25 October 2004). "The Discovery of the Microsomal Ethanol Oxidizing System and Its Physiologic and Pathologic Role". Drug Metabolism Reviews. 36 (3–4): 511–529.
- Kay J, Weitzman PD (1987). Krebs' citric acid cycle: half a century and still turning. London: Biochemical Society. pp. 25
Further Reading