By Vidya Rajan, Columnist, The Times
Tipple. The season is the reason. Well, with party season behind us now, let’s delve into the ubiquity of alcohol during the holidays. It is considered a conversational lubricant and socially acceptable to drink in a group setting, but it is considered a problem when someone drinks alone without an interlocutor, or for the purpose of getting drunk. It can also get costly – a 1926 vintage of Macallan whisky, sold for a cool $2.7 million in 2023. Does it taste that much better than a garden-variety Macallan? Does the person who bought it even plan to drink it? Be that as it may, there is a metabolic aspect that I want to briefly touch upon, because alcohol is a bioactive chemical.
Chemically, the term ‘alcohol’ describes any molecule that contains a hydroxyl (–OH group, where O stands for oxygen, H stands for hydrogen) attached to a carbon backbone. There can be long chain (aliphatic) and ring (aromatic) alcohols, and multiple –OH groups on a single molecule. The longer and more complex alcohols do not easily mix with water for drinking, they are usually unpalatable, and many are toxic even in small doses. That narrows us down to the three easily miscible alcohols: propanol (three carbon atoms and a size of 60 g/mol); ethanol (two carbon atoms and a size of 46 g/mol) and methanol (one carbon atom and a size of 36 g/mol). The molecules people can mix with water for a drink are propanol, ethanol and methanol. Let’s look at each of them.
A type of propanol is isopropyl alcohol used in first aid and in hand sanitizers. It is a serious contender for an award for most alcohol poisoning visits to the ER. There are two versions of propanol, called 1-propanol and 2-propanol. Both are small and are absorbed by the gastrointestinal system, from where they travel to the liver and get metabolized by alcohol dehydrogenases (multiple isoforms may be present), which removes an –H group, thereby oxidizing the molecules to different end products. 1-propanol gets metabolized to propionic acid, and acids cause acidosis. Its metabolic products travel into the bloodstream, enter the kidneys and respiratory system and cause failure.[1],[2] In the reaction, the intermediates are in regular font, and the enzymes are shown in italics:
1-propanol(alcohol dehydrogenase)propionaldehyde(aldehyde dehydrogenase)propionic acid(Krebs’ Cycle enzymes)CO2+H2O.
2-propanol is converted into acetone, the acrid stuff that is in nail polish remover, causing ketosis. Acetone is not further metabolized, and it is much more toxic for that reason. Do not drink Purell and do not let your friends drink it either. The reaction is: 2-propanol(alcohol dehydrogenase)acetone
Ethanol, which has two carbon atoms, is metabolized by alcohol dehydrogenase first to acetaldehyde and then to acetic acid (vinegar). The reaction is:
Ethanol(alcohol dehydrogenase)acetaldehyde(aldehyde dehydrogenase)acetic acidacetate ion(acetyl CoA synthase)acetyl CoA(Krebs’ Cycle enzymes)CO2+H2O.
To the biochemically inclined, the term “acetyl” will be familiar as a 2-carbon metabolic intermediate in many cycles where it is usually combined with another molecule called CoA which makes it usable. Acetyl CoA is cleaved off from fats to provide energy; it is joined together to make lipids for membranes, vitamin A for vision, or adipose for storage. But acetyl CoA, the metabolic intermediate, is not the same as acetaldehyde, a toxin which can kill liver cells. Acetaldehyde can be further oxidized to acetic acid and then to acetate ion. This acetate ion can be modified to the metabolic intermediate, acetyl CoA and used to make fat, which is why people who drink a lot gain weight. They can also get fatty liver on top of cirrhosis (dead cell patches in the liver), adding insult to injury. And possibly death too, because life depends on the liver. There, I snuck in a pun.
Methanol, which contains a single carbon atom joined up to –OH is a very potent toxin. Because of its small size, it is also readily absorbed. Consume it, and you’ll visit either the ER or be hauled to the morgue. In the liver, after oxidation by alcohol dehydrogenase, formaldehyde is produced. The reaction is:
Methanol(alcohol dehydrogenase)formaldehyde(aldehyde dehydrogenase)formic acid(Krebs’ Cycle enzymes)CO2+H2O.
You may know formaldehyde as the pickling solution in those yellowing jars of preserved organs and animal specimens in zoology labs. And should you choose to consume methanol, your liver is now being put through that same process. Some of that formaldehyde is oxidized further to formic acid. Acids cause acidosis, but formic acid is a small molecule that also causes cell toxicity resulting in blindness. It is also potent: many ants use it as a painful repellent, spraying it from their poison glands into wounds. No doubt you also recognize it as the chemical that beekeepers use to treat for Varroa mites.
There are three related functions that are affected by ethanol consumption: cognitive ability, motor function, and behavioral outcomes. These abilities are regulated in the prefrontal cortex, cerebellum, and thalamus, respectively. In addition, upon the ingestion of alcohol, the uptake of glucose (which is what the brain uses as food) decreased, particularly in the visual cortex and cerebellum; however, cerebral blood flow increased to the frontal and temporal cortex. In normal drinkers, the effect of alcohol on these regions was studied. A process called “neurocoupling”, meaning the ability of neurons to talk to each other was measured in each of these brain regions (by fMRI). After alcohol ingestion, neurocoupling decreased in the prefrontal cortex (showing a decrease in cognitive skills), but increased in the thalamus and the cerebellum. These may be connected too – the cerebellum also talks to the thalamus, linking the impairment of cerebellar neurons to altered mood and behavior, which is manifested via the thalamus. The reverse is also true, that the increased neurocoupling in the thalamus changes motor performance. The authors of the study put this down to the thalamus trying to cope with impaired motor functions by “unsuccessful compensatory activity”. Seems that the brain tries to fool itself! There is also an increase in dopaminergic signaling, providing the shot of “reward” due to dopamine release. The word “dope” could mean two things here! Depending on levels of alcohol and regions affected, the mood can range from pleasant to dizzy to restless to sedated. What of cognition? This is really simple – it decreases. But the picture is complicated by an increase in faster performance in heavy drinkers, but not light drinkers. Thus, heavy drinkers probably show more confidence in doing something by doing it faster (males show a greater effect), but their performance still stinks.[3]
Invertebrates are also sensitive to the action of alcohol. Just as in humans, alcohol binds to neurons in the central nervous system, depresses their activity, and consequentially slows down reflexes and alters their mood. Many bees and ants die when exposed to high levels of alcohol. However, the social Oriental hornet, Vespa orientalis, is a party-cularly (see what I did there?) robust species in terms of alcohol tolerance. A diet of 80% alcohol affected its lifespan not at all, whereas other wasps and honeybees died on the same diet within a matter of 24 hours. Even though honeybees can slowly adapt to alcohol – honeybees exposed to alcohol previously metabolized it faster.[4] The reason that hornets don’t is that they have many copies of alcohol dehydrogenase (ADH). However, wasps cannot taste the alcohol or get intoxicated.[5],[6] Then again, they are social hornets, and heavy drinking may be part of their party culture. Ha ha.
It’s not only humans who suffer the effects of alcohol – apparently many other animals also do; not a surprise – after all their brains are similarly wired. And many like the sensation of being ‘drunk’ so much they will seek alcohol in spoiling fruit. The marula fruit in Southern Africa is such a draw. The fruit is also sought by hungry animals earlier in the season. But if an abundance of fruit causes a lot to spoil and fall from the tree, they become little fermentation chambers. They are also on the ground and are snapped up by a variety of different animals. What is funny, of course, is that drunken animals behave a lot like their human counterparts. Elephants are now known to get more quickly drunk on less alcohol. This is attributed to elephants missing a gene, ADH7, for a version of the enzyme alcohol dehydrogenase that breaks down alcohol, so they get drunk on a relatively small amount of alcohol. Consider elephants that get drunk and wasps that don’t. Nature does play its little jokes.
Video: Intoxication by marula fruit.[7]
I will leave you with a couple of inebriation jokes (thanks to Reddit):
I can walk from my house to the pub in 5 minutes. But it takes me 20 minutes to walk home. The difference is staggering!
A man decides to teach his son about the evils of alcohol. He gets two glasses, fills one with bourbon and the other with water, and drops a worm into each glass. The worm in the water lives, and the one in bourbon dies. He looks at the son: “So what does that teach you about alcohol?” The son thinks for a second and replies: “If I drink bourbon, I won’t get worms.”
Happy New Year!
*Mea culpa for all the bad jokes and puns.
[1]. Rusyn, I. and Bataller, R. (2013). Alcohol and toxicity. Journal of Hepatology, [online] 59(2), pp.387–388. doi:https://doi.org/10.1016/j.jhep.2013.01.035.
[2] Vujasinovic, M., Kocar, M., Kramer, K., Bunc, M. and Brvar, M. (2007). Poisoning with 1-propanol and 2-propanol. Human & Experimental Toxicology, [online] 26(12), pp.975–978. doi:https://doi.org/10.1177/0960327107087794.
[3]. Shokri-Kojori E, Tomasi D, Wiers CE, Wang GJ, Volkow ND. Alcohol affects brain functional connectivity and its coupling with behavior: greater effects in male heavy drinkers. Molecular psychiatry. 2017 Aug;22(8):1185-95.
[4]. Miler, K., Kuszewska, K., Privalova, V. and Woyciechowski, M. (2018). Honeybees show adaptive reactions to ethanol exposure. Scientific Reports, 8(1). doi:https://doi.org/10.1038/s41598-018-27117-6.
[5]. Berkowitz, R. (2024). These Hornets Can Thrive on Just Alcohol without Getting Buzzed. [online] Scientific American. Available at: https://www.scientificamerican.com/article/these-hornets-can-thrive-on-just-alcohol-without-getting-buzzed/.
[6]. Bouchebti, S., Gershon, Y., Gordin, A., Huchon, D. and Levin, E. (2024). Tolerance and efficient metabolization of extremely high ethanol concentrations by a social wasp. Proceedings of the National Academy of Sciences, [online] 121(44). doi:https://doi.org/10.1073/pnas.2410874121.
[7]. www.youtube.com. (n.d.). YouTube. [online] Available at: https://www.youtube.com/embed/8MxNLg3rCdw?feature=oembed [Accessed 25 Dec. 2024].
