The cytochrome P450 enzyme system (commonly abbreviated as CYP or P450) is a crucial group of enzymes in the human body, primarily responsible for the metabolism of many xenobiotics (external compounds) and endogenous compounds. The primary roles of P450 enzymes in the body are demonstrated through two main tasks: drug metabolism and the metabolism of endogenous substances. In drug metabolism, CYP450 participates in the oxidation of organic compounds, aiding in the transformation and elimination of drugs from the body. This includes both the activation and detoxification of substances. Additionally, CYP450 is involved in the metabolism of hormones, cholesterol, and fatty acids. These enzymes play a significant role in maintaining homeostasis and regulating physiological processes. P450 enzymes contain heme, which catalyzes the direct functionalization of C-H bonds using molecular oxygen and electrons provided by redox partners such as diflavin-containing NADPH-P450 reductase (CPR).
Figure 1. Structure of the enzyme CYP2E1, a representative enzyme of the P450 enzyme system in the human body. (https://www.sinobiological.com/resource/cyp2e1/proteins)
Of the 57 known functional CYP enzymes in the human body, isoforms belonging to the CYP1, CYP2, and CYP3 families are responsible for metabolizing about 80% of clinical drugs. These include CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A4, and CYP3A5; with CYP3A4 and CYP2D6 contributing to more than 50% of CYP-related drug metabolism.
Figure 2. Fraction of specific CYP isoforms contribution to 248 drug metabolisms. (ZHAO, Mingzhe, et al., 2021)
In clinical practice, research on the P450 enzyme system helps doctors personalize treatment based on the metabolic characteristics of each patient, especially in cases involving multiple medications. Additionally, understanding the activity of these enzymes aids in predicting and preventing adverse reactions and drug toxicity, thereby improving treatment safety. The interaction between food, drugs, and the cytochrome P450 enzyme system is particularly important. The interaction between ingested food and the CYP450 system can affect drug metabolism in the body, leading to changes in the efficacy and safety of various drugs. There are three main mechanisms of interaction: inhibition, induction, and changes in gene expression. Some foods can inhibit CYP450 enzyme activity, reducing drug metabolism and leading to increased drug concentrations in the blood and a higher risk of toxicity. Conversely, other foods can induce CYP450 enzymes, increasing drug metabolism rates and reducing drug concentrations in the blood, thereby decreasing therapeutic efficacy. Additionally, food can affect the gene expression of CYP450 enzymes, altering the amount of enzyme available for drug metabolism. For example, green tea extract has been reported to inhibit the activity of CYP2C9, CYP2D6, and CYP3A4 in human liver microsomes. Alcohol can induce CYP2E1, increasing the metabolism rate of certain drugs like paracetamol, and producing toxic metabolites harmful to the liver when taken in excessive amounts. Garlic, a very common spice, contains compounds that induce CYP450 enzymes such as CYP3A4, CYP2E1, and CYP2D6, which can reduce the concentrations of some drugs like antifungals and anticonvulsants, thereby reducing their therapeutic effectiveness. Therefore, during treatment and medication use, patients should inform their doctors about all the foods, beverages, and supplements they are consuming so the doctors can consider potential interactions. Additionally, patients should adhere to dietary guidelines while taking medications to avoid unwanted interactions.
References:
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LE, Thien‐Kim, et al. Solar‐Powered Whole‐Cell P450 Catalytic Platform for C‐Hydroxylation Reactions. ChemSusChem, 2021, 14.15: 3054-3058.
NISHIKAWA, Masataka, et al. Effects of continuous ingestion of green tea or grape seed extracts on the pharmacokinetics of midazolam. Drug metabolism and pharmacokinetics, 2004, 19.4: 280-289.
SASAKI, Takamitsu, et al. Effect of health foods on cytochrome P450-mediated drug metabolism. Journal of pharmaceutical health care and sciences, 2017, 3: 1-11.
ZHAO, Mingzhe, et al. Cytochrome P450 enzymes and drug metabolism in humans. International journal of molecular sciences, 2021, 22.23: 12808.
ZHOU, Shufeng, et al. Interactions of herbs with cytochrome P450. Drug metabolism reviews, 2003, 35.1: 35-98.
Le Thien Kim - Faculty of food science and technology