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Wine is an essential drink for gatherings or feasts, but some people fall for a cup, and some people are not drunk for a thousand cups. Andre the Giant, a Frenchman, his record was to drink 120 to 150 bottles of beer at a time! He can consume 41 liters of beer in 6 hours. Why do some people get drunk faster than others?
As we all know, the main ingredient of all kinds of wine is alcohol. With the problem above, we first learn the process of alcohol metabolism. And then we will have a better understanding of the causes of drunkness, individual differences in alcohol consumption, the mechanism of dispelling the effects of alcohol, and the pros and cons of drinking.
And now it's time to share what we has discovered. Read the following contents and you will find out the truth.
1.Alcohol metabolism in the body
2.Why does alcohol make some people drunk?
3.Why are others not drunk even they drink much more than you?
The scientific name of alcohol is ethanol. Ethanol is both water-soluble and fat-soluble. It means that when a person drinks wine, the alcohol passes through the esophagus, stomach, intestines and other organs directly through the biofilm and enters the blood circulation, and is quickly transported to various tissues and organs throughout the body for metabolism. As the saying goes, the wine is in the intestines. The ethanol absorbed by the stomach and intestines circulates into the liver through the blood. More than 90 percent of the ethanol is metabolized in the liver, and less than 10 percent of the ethanol is excreted directly through the kidneys, lungs, or sweat.
There are three metabolic pathways in ethanol in hepatocytes, and each pathway is localized within a specific subcellular structure.
When the concentration of ethanol in the blood is low, ethanol is oxidized to acetaldehyde under the catalysis of alcohol dehydrogenase (ADH), and this process is completed in the cytoplasm. The reaction equation is: CH3CH2OH + NAD+ → CH3CH0 + NADH + H+
When the ethanol concentration is too high, the ADH pathway cannot completely complete the metabolism of ethanol. At this time, the body will induce the expression of the cytochrome P450 gene to produce the enzyme CYP2E1 (P450-2EI), which initiates another metabolic pathway, which is through the oxidation of microsomal ethanol in the endoplasmic reticulum. The enzyme system (MEOS) is metabolized to oxidatively decompose ethanol into acetaldehyde. The reaction equation is: CH3CH2OH + NADPH + O2 + H+ → CH3CH0 + NADP++ 2H2O
The production of reactive oxygen species (ROS) when CYP2EI oxidizes ethanol is an important mechanism leading to liver injury. Ethanol is metabolized through the MEOS pathway, which not only does not produce energy, but also increases the consumption of oxygen, leading to energy failure in the liver, injury to liver cells, and even death.
This pathway is localized in the peroxidase body and is initiated when ethanol is excess. The reaction equation is: CH3CH2OH + H2O2 → CH3CH0 + 2H2O
Among them, ADH and MEOS are the main pathways for ethanol metabolism.
In the mitochondria, acetaldehyde is converted to acetic acid by acetaldehyde dehydrogenase (ALDH). The reaction equation is: CH3CH0 + NAD+ + H2O → CH3COOH + NADH + H+
The resulting acetic acid enters the tricarboxylic acid cycle in the form of acetyl CoA, which is oxidized to H2O, CO2 while releasing a large amount of ATP. The reaction equation is: CH3COOH + CoA + ATP → Acetyl-CoA + AMP + PPi; Acetyl-CoA + 3 NAD + FAD + GDP + Pi+ 2 H2O → CoA-SH + 3 NADH + 3 H + + FADH2+ GTP + 2 CO2
Figure: The process of alcohol metabolism
(sourcing: https://pubs.niaaa.nih.gov/publications/arcr351/6-16.htm)
Alcohol is a neurotropic substance that paralyzes brain cells, suppresses the central nervous system, and interferes with the brain's communication pathways. These interruptions can change moods and behaviors, making people unresponsive, unconscious, and slow-moving. In addition, acetaldehyde, one of the intermediate metabolites of ethanol, builds up in the body, causing blushing, dizziness, and vomiting. These are common reactions to drunkness.
Ethanol enters the brain through the bloodstream and then attaches to the glutamate receptors in the brain's neural circuits. Glutamate is a neurotransmitter that normally stimulates neurons. Ethanol does not allow glutamate to become active, which slows the brain's response to stimuli. Ethanol also binds to the GABA (gamma-aminobutyric acid) receptor and activates the GABA receptor, which makes people feel calm and drowsy, so the brain's function is further slowed down.
In the general human body, there are alcohol dehydrogenases, and the quantitative activity is substantially equal. However, due to differences in races and individuals, the activity and quantity of ALDH2 are different. Half of Asians have weaker ALDH activity, so the intermediate metabolite--acetaldehyde, accumulates in the body after drinking, which causes the concentration of acetaldehyde in the blood to rise rapidly, resulting in facial and systemic flushing, palpitations, volatility, and vomiting. They are typical drunk reactions.
After 1 to 2 hours, the red color on their faces will gradually go to the legs. This is caused by the P450 in the liver slowly converting acetaldehyde into acetic acid, which is then metabolized by entering the TCA cycle.
| The alcohol concentration in the blood (％) | Drunk Reactions |
|---|---|
| 0.05 | Slightly drunk, happy mood, more words, eye, and finger coordination is affected |
| 0.1 | Hypoesthesia, shambling gait, emotional instability, aggressive behavior (acute alcoholism) |
| 0.2 | Rough conduct, foul words, liable to cause troubles |
| 0.3 | Slurred speech, vomiting and getting drunk |
The key factor of some people do not get drunk despite of having a lot alcohol is due to ALDH.
A study by the US National Academy of Sciences showed that the amount of alcohol and the presence or absence of alcohol addiction are not developed by the exercise of the day after tomorrow, but by the "drinking gene"-ALDH, which can affect people's response to alcohol.
According to the alcohol metabolism pathway, we know that alcohol is first oxidized to acetaldehyde by ADH, and the content and activity of individual alcohol dehydrogenase are not much different, so this step will not be different in the population. After that, acetaldehyde must be converted to acetic acid under the catalysis of ALDH, and the activity of ALDH in each person varies from person to person, which is the key reason for the difference in alcohol consumption.
People with high ALDH activity have a strong alcohol metabolism capacity; those with low ALDH activity have less ability to metabolize alcohol. The level of ALDH activity is mainly related to heredity, and sometimes it can be induced by alcohol. Long-term drinking boosts the activity of this enzyme, thus increasing the amount of alcohol.
In addition, people who regularly drink large amounts of alcohol have higher MEOS system activity and better metabolism and tolerance to alcohol. This is the scientific evidence that alcohol consumption can be trained.
The general mechanism of the hangover is: stimulate the body to produce acetaldehyde dehydrogenase and increase the enzyme activity, accelerate the oxidation of acetaldehyde to acetic acid, and directly act on the produced acetaldehyde to reduce the toxic effect of acetaldehyde on the body.
Generally, adults can digest 15 ml of alcohol per hour. Drinking too much alcohol over a long period of time or at one sitting could damage the heart, liver and pancreas, and could elevate the risk of cancer. Long-term drinking also make one person addictive and dependent in alcohol.
Brain: Excess alcohol disturbs one's mind and affects emotions and memory. At the same time, it elevates the risk of stroke and dementia.
Heart: Drinking a lot can damage the heart, leading to heart attacks such as high blood pressure and cardiomyopathy.
Liver: Long-term heavy drinking can cause alcoholic hepatitis and increase the risk of cirrhosis.
Cancer: Head and neck cancer, esophageal cancer, liver cancer, breast cancer, and colorectal cancer also occur frequently in those who prefer to drink.
Acetaldehyde produced during alcohol metabolism is more toxic to humans than ethanol, which is 10 times more toxic than ethanol. Acetaldehyde has great hepatotoxicity, mainly causing changes in liver cells. Alcoholic cirrhosis is the result of the direct action of acetaldehyde on hepatocytes. Acetaldehyde has general anesthetic effects and can also cause drowsiness, paralysis, hallucinations, and loss of intelligence and large doses can even cause death through respiratory paralysis.
Certainly, it is good for the human body to drink wine occasionally. Here list some benefits of drinking little alcohol.
| Alcohol categories | Benefits |
|---|---|
| Liquor | Smooth blood circulation, scattered blood stasis and blood circulation, phlegm and cold, spleen and warm stomach |
| Yellow wine | Rich in nutrients, contains more than 18 kinds of amino acids, including 8 kinds of essential amino acids |
| Wine | Abundant amino acid and vitamin content; soften blood vessels and protect the heart |
| Beer | "Liquid bread"; promote blood circulation, appetite, protect the heart, help digestion, eliminate fatigue, clearing heat and diuresis |
To some extent, alcohol is a good thing. No matter it is wine or beer, they bring us happy moments. However, it is recommended to drink moderately, especially for those who are easily drunk. After all, the vast majority are not Andre the Giant.
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