The human body processes substances like alcohol through enzymatic reactions. When alcohol (ethanol) is consumed, a specific metabolic pathway breaks it down. In biology, an “inhibitor” is a substance that interferes with or slows an enzyme’s activity. This article explores how the body handles alcohol and discusses alcohol dehydrogenase inhibitors, which disrupt this process for medical purposes.
Alcohol Metabolism and the Role of ADH
Alcohol metabolism primarily occurs in the liver. Here, alcohol dehydrogenase (ADH) is the first enzyme to break down ethanol. ADH converts ethanol into acetaldehyde, a highly reactive and toxic compound.
Acetaldehyde is harmful to cells and can cause adverse effects if it accumulates. The body’s second enzyme, aldehyde dehydrogenase (ALDH), converts acetaldehyde into acetate. Acetate is a less toxic substance that can then be broken down and eliminated from the body.
Understanding Alcohol Dehydrogenase Inhibitors
Alcohol dehydrogenase inhibitors block or slow the ADH enzyme’s activity. They bind to the ADH enzyme’s active site, preventing it from interacting with its alcohol substrate. This binding can be competitive, where the inhibitor competes directly with alcohol, or non-competitive, where it binds elsewhere on the enzyme, altering its shape and reducing activity.
Inhibiting ADH leads to the accumulation of the parent alcohol, such as ethanol, in the body. In poisoning cases, this accumulation is beneficial as it prevents the formation of more toxic byproducts.
Key Medical Applications
The primary medical use of alcohol dehydrogenase inhibitors is in treating methanol and ethylene glycol poisonings. These substances are metabolized by ADH into harmful compounds. For instance, ADH converts methanol into formaldehyde, which becomes formic acid. Formic acid causes severe metabolic acidosis and can lead to optic nerve damage and visual impairment.
Similarly, ADH metabolizes ethylene glycol into glycoaldehyde, then oxidized into glycolate and oxalate. These metabolites can cause metabolic acidosis and kidney damage from calcium oxalate crystal formation. By inhibiting ADH, these inhibitors prevent the formation of these toxic metabolites, allowing the parent alcohols to be excreted before causing harm. Fomepizole (4-methylpyrazole) is a key drug used as an antidote for both methanol and ethylene glycol poisoning.
Considerations for Use
Alcohol dehydrogenase inhibitors like fomepizole are administered intravenously in emergency settings. Their use requires strict medical supervision, often in a hospital intensive care unit, due to the serious nature of the poisonings.
Potential side effects of fomepizole include headache, dizziness, nausea, and a metallic taste. It is important to distinguish ADH inhibitors from other alcohol-related medications like disulfiram. Disulfiram primarily inhibits aldehyde dehydrogenase (ALDH), leading to acetaldehyde buildup when alcohol is consumed. This causes unpleasant symptoms that discourage drinking, representing a different mechanism and medical application.