Alcohol Metabolism and Its Effects on the Body

Alcohol, also known as ethanol (EtOH), is a commonly used recreational drug that affects multiple organs in the body. When consumed, alcohol is rapidly absorbed into the bloodstream and can reach the brain in as little as 5 minutes.

The liver is the main site of alcohol metabolism, where it is broken down into acetaldehyde and acetate. This process can lead to damaging effects in the liver and other areas of the body. In this article I will examine how alcohol is metabolized, the enzymes involved, genetic factors that affect alcohol tolerance, and the harmful impacts alcohol metabolism can have on the liver and brain.

Absorption and Peak Alcohol Concentration

When alcohol is consumed orally, around 20% is absorbed rapidly from the stomach into the bloodstream. The remaining 80% is absorbed from the small intestine into the bloodstream. Because alcohol is water-soluble, it is transported quickly to all organs of the body after entering the blood.

After ingestion, peak alcohol concentration in the blood is reached within 30 minutes. A standard drink, defined as one containing approximately 14 grams of pure ethanol, results in a blood alcohol concentration (BAC) of about 20 milligrams per deciliter (mg/dL) in a 70 kg individual. The legal driving limit in many countries is 50 mg/dL, equating to around 2-3 standard drinks.

Key Enzymes Involved in Alcohol Metabolism

The liver is the primary site of alcohol metabolism, where over 80% of ingested alcohol is broken down. The main pathway involves two key enzymes:

• Alcohol dehydrogenase (ADH) – converts ethanol into acetaldehyde
• Aldehyde dehydrogenase (ALDH) – converts acetaldehyde into acetate

Both steps utilize the coenzyme NAD+ and generate NADH. ADH and ALDH are primarily active in liver cells called hepatocytes.

Genetic Factors Affecting Alcohol Tolerance

Genetic differences affect the activity levels of ADH and ALDH, impacting alcohol tolerance:

• Some people have increased ADH activity, generating high acetaldehyde levels
• Approximately 40% of East Asians have a defective ALDH enzyme, causing acetaldehyde buildup

Therefore, some individuals experience adverse effects like flushing at lower alcohol doses. Chronic drinkers can adapt by activating an alternate pathway using the CYP2E1 enzyme.

Harmful Effects of Alcohol Metabolism on the Liver

Excessive alcohol metabolism can damage the liver through:

• Generation of reactive oxygen species – these can directly harm liver cells
• Fatty liver formation – NADH and acetate production promotes fat synthesis
• Inflammation – bacterial toxins released from the gut travel to the liver and activate inflammatory cells

Brain Effects of Alcohol Metabolism

The high NADH/low NAD+ ratio generated during alcohol metabolism inhibits glycolysis, the brain’s primary energy source. This deprivation causes hunger pangs despite adequate nutrition. The brain interprets this as hypoglycemia and signals hunger.

Acetaldehyde also contributes to alcohol’s effects by binding neurotransmitter receptors and interfering with brain function.

Chronic Alcohol Abuse Can Damage

Alcohol metabolism primarily occurs in the liver but affects the entire body. Genetic differences account for varying alcohol tolerance among individuals. Chronic alcohol abuse can damage the liver through oxidative stress, fat accumulation, and inflammation. It also disrupts normal brain energy metabolism and neurotransmitter function. Understanding the mechanisms and consequences of alcohol metabolism provides insight into the short and long-term health impacts of alcohol consumption.