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We can all agree that alcohol is an important part of our culture, whether we like it or not. Birthdays, holidays, parties – you will be offered an alcoholic beverage on almost every special occasion one can think of. I confess that I accept an offer like that if the time and place are appropriate. Therefore, I as a casual consumer and a college student decided to look into how exactly alcohol interacts with the human body and why it has different effects on different people. Although many organic compounds are categorized as alcohols, people usually refer to ethyl alcohol or ethanol when using the word alcohol. This small molecule, made of a little more than a few carbon atoms is responsible for drunkenness. It is the active ingredient in alcoholic beverages and because of its simplicity, it can pass through biological membranes easier than some other, bigger compounds. After consumption alcohol lands in the stomach and is absorbed into the blood through the digestive tract, especially the small intestine. How much of it will be absorbed depends on how full the stomach is – after eating, the pyloric sphincter, which separates the stomach from the small intestine closes. That’s why the level of alcohol that reaches the blood after a big meal might only be a quarter from the same drink on an empty stomach. After absorption, alcohol is transported to the organs, especially those that get the most blood flow: the liver and the brain. It reaches the liver first where it is metabolized by several different pathways. The most common of these involves two enzymes—alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH). These enzymes help break apart the alcohol molecule, making it possible to eliminate it from the body. First, ADH metabolizes alcohol to acetaldehyde, which is a highly toxic substance and a known carcinogen. Fortunately, it is metabolized further in a second step, where it is broken down by ALDH to another, a less active by-product called acetate which then is broken down into water and carbon dioxide for easy elimination As I mentioned before, that’s just one of many different metabolic pathways, and many other enzymes contribute to alcohol breakdown. For example, the enzymes CYP2E1 and catalase also break down alcohol into acetaldehyde. However, CYP2E1 only is active after a person has consumed large amounts of alcohol, and catalase metabolizes only a small fraction of alcohol in the body As blood circulates, the liver eliminates alcohol continuously. If the amount of alcohol drunk is greater than the amount of alcohol the liver can break down in a certain period of time (which is on average about 10 g or one drink per hour) the remaining alcohol is reabsorbed into the bloodstream. When it finally reaches the brain, it starts to disrupt various mechanisms resulting in emotional, cognitive, and behavioral effects we associate with drunkenness. It causes a release of γ-aminobutyric acid (GABA), and it acts primarily at the GABAA receptors. GABA is the primary inhibitory neurotransmitter in the brain and is associated with the sedative effects of alcohol, which are very much in the style of anesthetic. On the other hand, it slows down the synthesis of glutamate, which is the primary excitatory neurotransmitter of the brain, and its inhibition further contributes to the sedative effects of alcohol. The combination of decreased glutamate and increased GABA synthesis is the reason for the feeling of relaxation at moderate doses, falling asleep at higher doses, and even death at toxic doses because of the obstruction of the brain activity necessary for survival. Alcohol also stimulates a small group of neurons that extends from the midbrain to the nucleus accumbens a region important for motivation. It prompts an increase of dopamine in the nucleus accumbens, which results in a well-known feeling of pleasure. It also causes some neurons to synthesize and release endorphins, elevated levels of which contribute to the euphoria and relaxation associated with alcohol consumption. The combination of all the mentioned effects is known as drunkenness which fades away when the liver's breakdown of alcohol outpaces the brain's absorption. However, the symptoms of alcohol consumption aren’t the same for every person. The level of drunkenness depends on the amount of alcohol drunk, physical characteristics, and genetics. By physical characteristics, I mainly mean weight and sex. If a man and a woman who are the same age and weigh the same were to drink the same amount during an identical meal, they would still have different blood alcohol concentrations. This is because women tend to have less blood – women generally have a higher percentage of fat, which requires less blood than muscle. A smaller blood volume, carrying the same amount of alcohol, means the concentration will be higher for women. Genetic differences in the liver's alcohol-processing enzymes also influence blood alcohol concentration. However, regular drinking can increase the production of these enzymes, contributing to tolerance. On the other hand, those who drink excessively for a long time may develop liver damage which has the opposite effect. Meanwhile, genetic differences in dopamine, GABA, and endorphin transmission may contribute to the risk of developing an alcohol use disorder. Those with naturally low dopamine or endorphin levels may self-medicate through drinking. Some people have a higher risk for excessive drinking due to a sensitive endorphin response that increases the pleasurable effects of alcohol, others have a variation in GABA transmission that makes them especially sensitive to the sedative effect of alcohol, which decreases their risk to develop disordered drinking. In summary: a small molecule can have a considerable effect on our bodies and can even be dangerous in excessive doses, but consuming it is so normalized that we don’t even realize it. Thank you for your attention and drink responsibly.