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Did you know? Why do drugs undergo amazing transformations in the liver?
Drugs have become an integral part of many people's daily lives. When we take drugs, how are these drugs converted and eliminated in the body? In fact, the human body's unique metabolic system, especially the liver, plays a crucial role in the metabolism of drugs. Drug metabolism refers to the metabolic breakdown of drugs in the organism, which is usually adjusted through a specialized enzyme system. This conversion process not only affects the efficacy of the drug, but also helps reduce potential toxicity. The biochemical mechanism behind it is quite complex.
The process of drug metabolism is one of the biotransformation pathways possessed by all organisms, and is crucial for the detoxification and release of each drug.
Three stages of drug metabolism
The metabolic process of drugs can be roughly divided into three main stages:
Phase 1 – Modification
In the first stage, specific enzymes introduce reactive or polar groups into the drug molecules. This process is usually catalyzed by the cytochrome P450 system, which is widely present in the liver and changes the structure of the drug through oxidation, reduction, carboxyl hydrolysis and other reactions. Some drugs will be activated at this stage and converted into pharmacologically active substances, but they may also be converted into toxic compounds. For example, in some cases, future research may find that the toxicity of these metabolites can affect the human body. .
Phase 2 – Combination
In the next second stage, the modified drug metabolites are combined with polar molecules, such as glutathione, sulfuric acid, amino acids, etc., to form larger molecular weight and less active conjugates. These conjugates are more water soluble and can be excreted more easily, further reducing toxicity. In this process, transport enzymes with broad specificity metabolize nearly all lipid-soluble compounds with nucleophilic or electrophilic groups.
The third stage – further modification and excretion
In the third stage, these conjugates undergo further processing. A common example is the processing of glutathione conjugates, resulting in the formation of acetylcysteine conjugates. The final product can be excreted out of the cell through transporters in the cell membrane, thereby achieving excretion.
This series of metabolic processes not only helps in the excretion of drugs, but also reduces possible toxic reactions. It is really an act of biochemical wisdom of the human body.
Detoxification mechanism of exogenous substances
The challenge with a detoxification system is that it must be able to remove an almost unlimited number of exogenous compounds, which often change over time. The detoxification system takes advantage of the hydrophobic characteristics of the cell membrane and a non-specific enzyme system to evolve an elegant solution. Since most hydrophilic molecules cannot penetrate the cell membrane, the removal of hydrophobic compounds is particularly important. This is why many living organisms have enzymes that can carry out corresponding transformation and removal through digestion, oxidation, etc.
The special role of the liver
The liver is the main organ for drug metabolism because it is the most important detoxification organ in the human body. Because the liver has a large blood flow and is the first to receive compounds absorbed through the intestines, its enzyme concentration is also higher than that of other organs. This explains why the metabolic efficiency of drugs is often affected by the liver before they enter the circulation system. If a drug is absorbed through the intestines and enters the liver veins, the so-called "first-pass effect" will occur, which makes the conversion of some drugs in the liver particularly significant.
Variables in drug metabolism
The metabolic rate of drugs is affected by many factors, including age, gender, individual differences, and disease status. Physiological factors can alter the performance of enzymes and affect the rate of drug metabolism. Certain genetic polymorphisms, such as variations in N-acetyltransferase, may make some individuals more susceptible to side effects when taking medications.
From a clinical perspective, such variation is critical to the implementation of personalized medicine, as it helps ensure that each patient receives a treatment plan that is suitable for him or her.
Conclusion
Drug metabolism is a typical biological process that utilizes abundant enzymes in the liver and other organs to continuously transform and excrete exogenous compounds. However, the variations and challenges existing in this process cannot be underestimated, making personalized treatment plans an important need for future medical care. So, how to more effectively improve the efficiency of drug metabolism and reduce potential harm will be a problem that future researchers need to face?
