Why is Methanol Toxic, But Not Ethanol?

methanol ethanol bottle of toxic liquid ftloscience post

Ethanol (alcohol) is a poison that is widely consumed all around the world. However, drinking methanol the same way leads to a different, irreversible kind of poisoning. We look at the chemistry and toxicity of ethanol and methanol, two very similar molecules that affect the body differently.

On its own, methanol toxicity is similar to ethanol (alcohol) toxicity. However, our liver breaks methanol down into deadly formic acid, a molecule that deprives our cells of oxygen. By the same process, ethanol is broken down into acetic acid (also known as vinegar), a much less toxic molecule. This is why methanol poisoning is a medical emergency.

How Methanol Gets into Our Alcohol

There have been many cases around the world of people experiencing methanol poisoning after consuming illegally sold alcoholic beverages. Especially in developing countries where small bars cannot afford the price of taxed liquor, they create their own.

One of the dangers of consuming moonshine—or ‘homemade alcohol’—is the risk that it might have been spiked with methanol or that methanol has formed as a side product of improper fermentation.

In normal fermentation processes, yeast (similar to those used in baking) turns glucose sugar into ethanol (alcohol) and carbon dioxide:

C_{6}H_{12}O_{6} \to  2\: C_{2}H_{5}OH + 2\: CO2

However, some strains of wild yeast (yes, there are different types) have a particular enzyme called pectin methyl esterase. Many fruits used in making alcoholic beverages contain pectin, another form of sugar. Wild yeasts therefore use their pectin methyl esterase enzymes to break down the available pectin to form methanol.

Very tiny amounts of methanol occur naturally in most alcoholic beverages without causing harm. The real issue occurs when wild yeasts are introduced into the fermentation through contamination, which is why commercial alcohol is made under sterile conditions.

orange juice squeeze cut cup pectin


Methanol vs. Ethanol Toxicity

Methanol Poisoning

When we drink methanol, the side effects can range from mild to severe. Symptoms of methanol poisoning include a slight intoxication (drunkenness) for 10 to 20 hours, followed by weakness, vomiting, pain, confusion, severe lowering of blood pH, ocular toxicity, and eventually coma and death1.

In fact, methanol and ethanol are very similar in terms of the toxicity of the molecule. Methanol is not very toxic, comparable to your everyday alcohol in that it inhibits brain functions through its central nervous system depressant properties.

Your body, however, tends to break foreign chemicals down so they can be removed—a process known as metabolism. One of the first steps in metabolism is oxidation.

Oxidation of Methanol to Formaldehyde

Methanol in the body quickly makes it way to the liver, where an enzyme called alcohol dehydrogenase breaks it down. This produces formaldehyde, a known carcinogen, but one that doesn’t pose any immediate dangers to our health2.

Alcohol dehydrogenase also works on ethanol, converting it into acetaldehyde, another aldehyde molecule with similar properties to formaldehyde. You can see the chemical structures in the first reaction below.

pathway alcohol aldehyde dehydrogenase methanol alcohol poisoning toxicity toxic

Formic Acid, The Real Killer

The real toxicity associated with methanol poisoning comes from converting formaldehyde to formic acid in the next process. Another enzyme in the liver, aldehyde dehydrogenase, spots the formaldehyde molecules and turns it into formic acid. This same enzyme is responsible for converting acetaldehyde (from the ethanol pathway) into acetic acid, or vinegar.

While the final product of ethanol, acetic acid, is non-toxic, the same cannot be said of the final product of methanol metabolism. Formic acid (also known as formate) deprives cells of oxygen and causes them to die. The molecule inhibits a key enzyme in our mitochondria, cytochrome c oxidase, that is responsible for respiration.

By blocking the respiratory pathway, formic acid causes nerve damage, blindness and even death. Now we know that methanol poisoning should really be known as formic acid poisoning!

Can Formic Acid Poisoning be Cured?

The outcome of methanol poisoning (or rather, formic acid poisoning) is actually quite good, but only if the patient receives treatment quickly. However, because the initial symptoms are also caused by ethanol, people might not realize they are suffering from methanol poisoning, which delays treatment.

The cure for formic acid poisoning comes in the form of a drug called fomepizole. Fomepizole blocks alcohol dehydrogenase from functioning properly, stopping the breakdown of methanol into formaldehyde, which disrupts the pathway.

Hemodialysis—the filtering of blood by a machine—can also accelerate the removal of blood methanol and formic acid, although hemodialysis equipment is usually only available in large hospitals.

If it’s in an emergency situation and fomepizole isn’t available, the patient can be given ethanol. I know, it sounds crazy! But hear me out.

Remember that ethanol and methanol both follow the same metabolic pathway? This means that by flooding our liver with ethanol, we can force the alcohol dehydrogenase enzyme to break down ethanol instead of methanol, blocking formaldehyde from forming. In this way, methanol is excreted via the kidneys before it can be converted into formaldehyde and formic acid.



Reference

  1. McMartin, K. E., Ambre, J. J., & Tephly, T. R. (1980). Methanol poisoning in human subjects: role for formic acid accumulation in the metabolic acidosis. The American journal of medicine, 68(3), 414-418.
  2. Kerns, W. D., Pavkov, K. L., Donofrio, D. J., Gralla, E. J., & Swenberg, J. A. (1983). Carcinogenicity of formaldehyde in rats and mice after long-term inhalation exposure. Cancer Research, 43(9), 4382-4392.

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