How does ethanol counteract the poisonous effects of methanol?

Answer 1

Most of the toxic effects of methanol [H3C-OH], are from the first metabolite, formaldehyde [ H2C=O], which occurs when the enzyme Alcohol Dehydrogenase (ADH) oxidizes methanol into formaldehyde and the hemiacetal [CH(OH)2] - the later spontaneously forms formaldehyde in the presence of water. There are 6 subtypes of ADH in humans, which vary based on race and genetics, but they all have a preferred substrate, ethanol, when compared to methanol.

When ethanol is given to someone who has consumed methanol, the active site of the enzyme ADH fits ethanol [CH3CH2OH] better than methanol [CH3OH]; the ethanol gets metabolized more often than the methanol. By occupying the active site on the enzyme with ethanol, the methanol is metabolized more slowly into the far more toxic metabolite, formaldehyde, than it would be if ethanol were not present. This gives the body a smaller amount of formaldehyde to deal with at any given time, and the toxic effects are more easily contained. The toxic effects of the smaller amount of formaldehyde do not cause irreversible damage because the cells that were the most sensitive to formaldehyde (the liver, the kidneys and the retinae) do not get as much damage and can repair themselves up to a point.

Now this is an important point as to why this procedure works: Most drugs follow first order kinetics, K1, meaning that the enzyme detoxifies a constant percentage of the drug in a certain period of time (the time for 50% of a drug to be metabolized is called the half-life or t1/2 ). But ethanol and methanol follow zero order kinetics(K0), meaning a certain amount (weight or volume) of the drug is metabolized in a fixed time, for ethanol, it is about 1 oz per hour.
For Advanced students who are interested in Enzymology, Pharmaceutical Sciences or Toxicology,, here are some additional pieces of information:
A)Now, realistically, all drugs follow first order kinetics K1 within a certain range, and zero order kinetics K0 when the enzyme is saturated (meaning there is far too much of the drug around and far too little enzyme, so that even if every active site on every enzyme were occupied at one time, there would still be lots of drug left over.) Most drugs have a physiologic/pharmacologic effect in the microgram -- gram range; alcohol is the exception. When alcohol gets metabolized below about one gram, we start to see first order kinetics K1 instead of zero order kinetics K0. I have been asked in class many times if there are any enzymes that follow K2 or second order kinetics, like when a co-factor such as a vitamin is involved (Vitamin A in the Krebs Cycle for Acetyl-CoA). The answer is emphatically, NO. The probability of three molecules meeting together at random in the correct orientation approaches zero. It would be such a rare event that you could not sustain life if this were required. The binding of a co-factor or other component to an enzyme is a separate step, and is unrelated to t1/2 because there is so much co-factor around compared to the drug, that for all intensive purposes, you can assume, under normal conditions, that the enzyme and co-factor are always bound together.

B)Ethanol is oxidized by ADH into acetaldehyde and ethylene glycol, both of which are far less toxic than formaldehyde (not non-toxic, however, just less toxic; all three compounds are relatively toxic with formaldehyde>ethylene glycol>acetaldehyde.) The drug Antabuse(disulfiram), inhibits the enzyme Aldehyde Dehydrogenase, which converts acetaldehyde into acetate or acetic acid (3% (v/v) acetic acid in water is vinegar). It is acetaldehyde that is partly responsible for hangovers and makes most people feel bad in the ethanol metabolism chain, not ethanol itself or acetic acid.

MobiusDick

Answer 2

Ethanol competes with methanol for the same enzyme, alcohol dehydrogenase, in the liver. By getting metabolized first, ethanol prevents methanol from being converted into its more toxic byproducts, such as formic acid. This gives the body more time to eliminate methanol safely.