What is the molecular basis of hangovers?

Question

Well, most of us have experienced the wonderful feeling of the dreaded hangover. How does it work exactly? I imagine it has something to do with dehydration but what are the underlying mechanisms?Extra points for explaining why mixing drinks makes it worse and why (or if) a hair of the dog (another drink) the next day can help. Someone once told me that hangovers are the first symptoms of withdrawal and if you drink (anecdotal evidence suggests that it should be the _same_ drink as the night before, but I doubt this is true) a small amount of alcohol, the symptoms are alleviated. I don't really see how that can be true.

Answer 1

Hey I'd be happy to answer this question! Drinking alcohol causes the pyruvate made from glycolysis to be converted to lactate by lactate dehydrogenase to regenerate NAD+ needed for glycolysis. Because alcohol does not utilize the kreb cycle, very little ATP gets created. On top of this reaction occurring, generally a person sleeps after consuming alcohol with very little food. During this fasting state, the liver synthesizes Ketone Bodies, acetoacetate is one of the interconvertible byproducts of KB synthesis and due to the lack of NAD+ the reaction gets pushed to making more acetoacetate. It is this molecule that is directly responsible for the nausea and "hangover" feeling the next day.

Answer 2

Good question! Dehydration due to excessive alcohol consumption is the cause of a hangover. In order to understand this mechanism, a little background in renal science is necessary. To put it very simply, water and other compounds are excreted by the kidney. The kidney mainly wants to get rid of toxins though, so many of the excreted compounds (including water) are reabsorbed. Reabsorption of water occurs when proteins called aquaporins are inserted into the membrane of kidney nephrons. Alcohol inhibits the insertion of these aquaporins, causing a lot less water to be reabsorbed. As a result, when you drink a lot of alcohol, your body is losing a lot of water. This is why you frequently pee large volumes of clear urine when you're drunk.

If you don't maintain your hydration, you can wake up the next morning feeling pretty bad. Make sure to drink something that's hydrating with electrolyes (such as Pedialyte) the next time you are drinking. It will likely make the next day a lot easier on you!