Xenobiotic metabolism: Difference between revisions

Latest revision as of 18:46, 23 March 2025

Xenobiotic Metabolism[edit]

Xenobiotic metabolism refers to the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry. These compounds include drugs, pollutants, and other synthetic chemicals. The metabolism of xenobiotics is crucial for their detoxification and elimination from the body, primarily occurring in the liver.

Phases of Xenobiotic Metabolism[edit]

Xenobiotic metabolism is generally divided into three phases: Phase I, Phase II, and Phase III.

Phase I Metabolism[edit]

Phase I reactions involve the introduction or unmasking of a functional group on the xenobiotic compound. This phase is primarily carried out by the cytochrome P450 enzyme family, which catalyzes reactions such as oxidation, reduction, and hydrolysis.

The CYP2C9 enzyme, a member of the cytochrome P450 family, is one of the key enzymes involved in the oxidation of xenobiotics. These reactions often result in the formation of more polar metabolites, which can be more easily excreted from the body.

Phase II Metabolism[edit]

Phase II reactions involve the conjugation of the xenobiotic or its Phase I metabolites with endogenous substrates, such as glucuronic acid, sulfate, or glutathione. These conjugation reactions increase the water solubility of the xenobiotics, facilitating their excretion in urine or bile.

Common Phase II enzymes include UDP-glucuronosyltransferases, sulfotransferases, and glutathione S-transferases. These enzymes play a critical role in detoxifying reactive metabolites that may have been generated during Phase I metabolism.

Phase III Metabolism[edit]

Phase III involves the transport of xenobiotics and their metabolites out of cells. This phase is mediated by various transport proteins, such as ABC transporters, which actively pump xenobiotics across cellular membranes.

Factors Affecting Xenobiotic Metabolism[edit]

Several factors can influence the rate and extent of xenobiotic metabolism, including:

Genetic Variability: Genetic polymorphisms in metabolic enzymes can lead to variations in xenobiotic metabolism among individuals.
Age and Sex: Metabolic capacity can vary with age and between sexes, affecting drug metabolism and toxicity.
Diet and Nutrition: Certain foods and nutrients can induce or inhibit metabolic enzymes, altering xenobiotic metabolism.
Environmental Factors: Exposure to other chemicals, such as smoking or alcohol, can affect enzyme activity.

Clinical Significance[edit]

Understanding xenobiotic metabolism is crucial for the development of pharmacokinetics and pharmacodynamics of drugs. It helps in predicting drug interactions, adverse effects, and individual responses to medications. Moreover, it is essential for assessing the risk of exposure to environmental toxins and pollutants.

Related Pages[edit]

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-'''Xenobiotic metabolism''' is the set of metabolic pathways that modify the chemical structure of xenobiotics, which are compounds foreign to an organism's normal biochemistry, such as drugs and poisons. These pathways are a form of biotransformation present in all major groups of organisms, and are considered to be of ancient origin. These reactions often act to detoxify poisonous compounds (although in some cases, bioactivation is possible).
+== Xenobiotic Metabolism ==
-== Overview ==
+[[File:Xenobiotic_metabolism.png|Xenobiotic metabolism|thumb|right]]
-[[Xenobiotics]] are compounds that are foreign to a living organism. They include substances like drugs, environmental pollutants, and natural compounds from plants and microorganisms. The body has developed various mechanisms to eliminate these substances, and xenobiotic metabolism is one of them.
+'''Xenobiotic metabolism''' refers to the set of metabolic pathways that modify the chemical structure of [[xenobiotics]], which are compounds foreign to an organism's normal biochemistry. These compounds include drugs, pollutants, and other synthetic chemicals. The metabolism of xenobiotics is crucial for their detoxification and elimination from the body, primarily occurring in the [[liver]].
 == Phases of Xenobiotic Metabolism ==
-Xenobiotic metabolism typically consists of three phases: [[Phase I reactions]], [[Phase II reactions]], and [[Phase III reactions]].
-=== Phase I Reactions ===
+Xenobiotic metabolism is generally divided into three phases: [[Phase I metabolism|Phase I]], [[Phase II metabolism|Phase II]], and [[Phase III metabolism|Phase III]].
-Phase I reactions (also termed nonsynthetic reactions) may occur by oxidation, reduction, hydrolysis, cyclization, and decyclization reactions. Oxidation involves the enzymatic addition of oxygen or removal of hydrogen, carried out by mixed function oxidases, often in the liver.
+=== Phase I Metabolism ===
+Phase I reactions involve the introduction or unmasking of a functional group on the xenobiotic compound. This phase is primarily carried out by the [[cytochrome P450]] enzyme family, which catalyzes reactions such as oxidation, reduction, and hydrolysis.
+[[File:CYP2C9_1OG2.png|CYP2C9 enzyme structure|thumb|left]]
+The [[CYP2C9]] enzyme, a member of the cytochrome P450 family, is one of the key enzymes involved in the oxidation of xenobiotics. These reactions often result in the formation of more polar metabolites, which can be more easily excreted from the body.
+=== Phase II Metabolism ===
+Phase II reactions involve the conjugation of the xenobiotic or its Phase I metabolites with endogenous substrates, such as [[glucuronic acid]], [[sulfate]], or [[glutathione]]. These conjugation reactions increase the water solubility of the xenobiotics, facilitating their excretion in urine or bile.
-=== Phase II Reactions ===
+Common Phase II enzymes include [[UDP-glucuronosyltransferase]]s, [[sulfotransferase]]s, and [[glutathione S-transferase]]s. These enzymes play a critical role in detoxifying reactive metabolites that may have been generated during Phase I metabolism.
-Phase II reactions (also termed conjugation reactions) involve the enzymatic conjugation of endogenous compounds, such as glucuronic acid or sulfate, to the xenobiotic.
-=== Phase III Reactions ===
+=== Phase III Metabolism ===
-Phase III reactions involve the further modification of the xenobiotic-conjugate to increase its water solubility for excretion.
-== Enzymes Involved ==
+Phase III involves the transport of xenobiotics and their metabolites out of cells. This phase is mediated by various transport proteins, such as [[ATP-binding cassette transporter|ABC transporters]], which actively pump xenobiotics across cellular membranes.
-The enzymes involved in xenobiotic metabolism are primarily located in the liver, but can also be found in other parts of the body. The most important of these enzymes are the [[cytochrome P450]] enzymes, which are responsible for the oxidation of xenobiotics.
+== Factors Affecting Xenobiotic Metabolism ==
+Several factors can influence the rate and extent of xenobiotic metabolism, including:
+* '''Genetic Variability''': Genetic polymorphisms in metabolic enzymes can lead to variations in xenobiotic metabolism among individuals.
+* '''Age and Sex''': Metabolic capacity can vary with age and between sexes, affecting drug metabolism and toxicity.
+* '''Diet and Nutrition''': Certain foods and nutrients can induce or inhibit metabolic enzymes, altering xenobiotic metabolism.
+* '''Environmental Factors''': Exposure to other chemicals, such as [[smoking]] or [[alcohol]], can affect enzyme activity.
 == Clinical Significance ==
-Understanding xenobiotic metabolism is important in [[pharmacology]] and [[toxicology]], as it can influence the efficacy and toxicity of drugs and other xenobiotics.
-== See Also ==
+Understanding xenobiotic metabolism is crucial for the development of [[pharmacokinetics]] and [[pharmacodynamics]] of drugs. It helps in predicting drug interactions, adverse effects, and individual responses to medications. Moreover, it is essential for assessing the risk of exposure to environmental toxins and pollutants.
+== Related Pages ==
+* [[Cytochrome P450]]
 * [[Drug metabolism]]
-* [[Metabolomics]]
+* [[Toxicology]]
-* [[Pharmacokinetics]]
+* [[Biotransformation]]
-== References ==
+{{Portal|Medicine}}
-<references />
+{{Portal|Biochemistry}}
-[[Category:Biochemistry]]
+[[Category:Metabolism]]
+[[Category:Toxicology]]
 [[Category:Pharmacology]]
-[[Category:Toxicology]]
-{{stub}}