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Ethanol + Tylenol = Carcinogen

Posted by naturalproductman on April 19, 2015

I thought it would be fun to talk about ethanol today. Structurally, ethanol is an interesting natural product because it is water but you just put an ethyl substituent on the oxygen. Ethanol’s boiling point is 78 degrees celsius – thus lowering the boiling point from water when a hydrogen bond donor is lost. Biosynthetically, ethanol comes from the 2 electron reduction of acetaldehyde, which is derived from the decarboxylation of pyruvate and pyruvate is a product of a 10-step breakdown of glucose (two moles of pyruvate from one mole of glucose).

Ethanol actually induces the expression of cytochrome P450 2E1 in our bodies, the enzyme which oxidizes ethanol to acetaldehyde then to acetic acid (vinegar?!). It must be our body’s way of removing ethanol, this interesting signalling molecule found to have many other interesting effects in our brain.

So it is the link between the two components (1. ethanol and 2. increased cytochrome P450 2E1 expression), which brings up the point: when drinking alcohol, don’t take Tylenol, which is also a substrate for cytochrome P450 2E1. Tylenol (also known as acetaminophen), is N-acetyl-para-amino-phenol. So it’s a phenolic compound which can become oxidized to the quinone by electron transfer to the iron center of P450 2E1. This reactive electrophilic quinone (also known as N-acetyl-para-benzoquinone imine or NAPQI) can form DNA adducts and mutation during DNA replication, leading to cancer. The antidote for NAPQI over exposure is N-acetylcysteine, which reacts with NAPQI in the same nucleophilic manner that DNA adducts to NAPQI. Except that a sulfur nucleophile from N-acetyl-cysteine is much better than the aza-nucleophile from any of the DNA bases. Not only does NAPQI introduce  mutations in our genome, NAPQI depletes glutathione, an important antioxidant in our bodies.

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