Oxidation, Reduction, and Hydrolysis of xenobiotics.
The polar and reactive group on the molecule can subsequently undergo conjugation.
Glucuronides, sulfates, GSH derivatives, and other derivatives.
Lipophilic toxicants are hard for the body to eliminate and can accumulate to hazardous levels.
Detoxification refers to reactions that convert certain substances into compounds that are more water soluble and thus readily excreted from the body, reducing toxicity.
In the mitochondria, found in the liver, heart, CNS, and vascular tissue.
Phase 1 involves chemical modification, and Phase 2 involves conjugation following chemical modification.
Conjugation is the addition of endogenous groups to foreign compounds, making them more polar and less lipid soluble, which increases excretion and reduces toxicity.
Monoamine oxidase
A series of biochemical reactions occurring in the body to convert foreign (often toxic) compounds to nontoxic or less toxic (more easily excretable) forms.
Detoxification is also called drug metabolism or biotransformation.
Detoxification is the process of converting toxic xenobiotics or metabolites into less harmful and excretable, water-soluble substances.
S-Adenosyl Methionine
Non-microsomal oxidation refers to oxidation processes that occur outside the microsomal system.
Tyramine
Detoxification occurs primarily in the liver and involves various cell organelles, enzymes, and coenzymes/cofactors.
Oxygen and glutathione are examples of co-substrates needed for metabolic mechanisms.
The product is more polar, less lipid soluble, which facilitates excretion and reduces toxicity.
Detoxification refers to the biochemical processes that render noxious substances less harmful and more water soluble.
Hydroxylation reactions.
Glutathione acts as a sulfur donor and provides electrons to neutralize hazards.
Hormones such as thyroid hormone and steroid hormones like estrogen, testosterone, and aldosterone are inactivated in the liver, preparing them for removal from the blood through the kidney.
They catalyze oxidation reactions, converting xenobiotics into hydroxylated xenobiotics.
In the smooth endoplasmic reticulum membranes of the liver, kidney, lung, and intestine.
Morphine, Dapsone, Chloramphenicol, and Indomethacin.
Sulphate esters are much more soluble.
Phase I and Phase II drug metabolism.
The cytochrome P450 enzyme system is crucial for the detoxification process in the human body, facilitating the metabolism of various substances.
Phase 1 reactions involve the modification of substances, while phase 2 reactions involve conjugation to make them more water-soluble for excretion.
Phase I reactions involve the modification of toxic substances through oxidation, reduction, or hydrolysis, primarily facilitated by cytochrome P450 enzymes.
NAD-linked alcohol dehydrogenase is the enzyme linked to alcohol oxidation.
Flavoprotein enzymes
Cytochrome P450 catalyzes oxidation reactions that detoxify substances, specifically in the microsomal ER of the liver.
It introduces one atom of oxygen into xenobiotics while reducing the other atom to water.
Non-microsomal oxidation, specifically amine oxidation.
Isoniazide is used for the treatment of Tuberculosis and can be acetylated to form Acetyl Sulphnilamide.
The reaction is X-H + O2 + NADPH + H+ + Cytochrome P450 → X-OH + H2O + NADP+.
It is present in microsomes from the liver, adrenal gland, and mitochondria.
PAPS acts as a sulfur donor in the detoxification process.
Mixed function oxidases.
Modes of drug elimination and bioactive metabolites.
Enterohepatic cycle.
The levels of particular enzymes are crucial for the control of metabolism mechanisms.
Non-polar metabolites are substances that are not soluble in water and may be less easily excreted from the body.
The liver breaks down drugs such as penicillin and erythromycin into harmless wastes, which are then excreted.
The formation of Phenol Phenyl Sulphate is catalyzed by Sulpho transferase.
Conjugation of xenobiotics and their excretion.
It acts as an active substance that conjugates with xenobiotics to form glucuronides for excretion.
Xenobiotics are foreign or strange compounds that undergo metabolism in the body.
The absorption peak is at 450 nm.
Phase I reactions include oxidation, reduction, hydroxylation, and hydrolysis.
Benzoyl Glucuronide + UDP
Hydroxylation reactions, which are part of Phase 1 detoxification.
The detoxification mechanism results in elimination (excretion) of substances.
Non-microsomal oxidation refers to metabolic processes that occur outside of the microsomal enzyme system, often involving enzymes like alcohol and aldehyde dehydrogenase.
Monoamine oxidases are the enzymes involved in monoamine oxidation.
Biotransformation reactions generally generate more polar metabolites that are readily excreted from the body.
Phenyl Glutamine
Indol
Yes, detoxified products may be more toxic but are more water soluble and easily excretable.
S-Adenosyl Homocysteine
Glucoronyl transferase.
Norepinephrine
It is a hemoprotein with a heme prosthetic group.
It is associated with the smooth endoplasmic reticulum of liver cells and the small intestine.
Phenobarbitone induces the Cytochrome P450 enzyme.
Cyanide (toxic) reacts with sodium thiosulphate to produce thiocynates (less toxic) and sodium sulfate.
Cofactors such as NADPH are important for controlling metabolism.
An example is the biotransformation of vinyl chloride to vinyl chloride epoxide, which can covalently bind to DNA and RNA, potentially leading to liver cancer.
Alcohol and aldehyde dehydrogenase are the key enzymes involved in the oxidation of alcohol and aldehyde.
Endogenous groups are added to a suitable functional group present on the foreign molecule or introduced by phase 1 metabolism.
Phase II reactions involve conjugation processes where modified substances from Phase I are linked to another substance to increase water solubility for excretion.
No, toxicity may not be eliminated but can be reduced through detoxification.
Bioactivation refers to the metabolic activation of xenobiotics or drugs into reactive, toxic compounds.
Methanol and formaldehyde.
In the microsomal endoplasmic reticulum (ER) of the liver.
Sulphate conjugation is catalyzed by the sulphotransferase enzyme, located in the cytosol and found in the liver, GI mucosa, and kidney.
UDP-glucuronosyl transferase (glucuronyl transferase) catalyzes the conjugation.
NADPH is needed for the addition of an OH group.
They possess broad substrate specificity.
Phenyl Aceturic acid
The formula for thiocynates is SCN.
Substances produced in the large intestine from bacterial enzymatic action and end products of metabolism.
Glutathione is a tripeptide composed of glutamic acid, cysteine, and glycine.
Biotransformation is the process where a substance is changed from one chemical to another by a chemical reaction within the body.
Biliary excretion, renal excretion, respiration (exhalation), and sweat.
The glutathione conjugate may be excreted or undergo further metabolization.
Detoxified products may be more toxic than the original form but are more water soluble (polar) and easily excretable.
NAD-linked aldehyde dehydrogenase is responsible for aldehyde oxidation.
Cadaverine
Substrates include aliphatic alcohols, phenols, aromatic amines, steroids, and carbohydrates.
The sulphate donor is 3'-phosphoadenosyl-5'-phosphosulphate (PAPS), formed from inorganic sulphate and ATP.
The main excretion pathways include the kidneys, feces, and expired air.
The most common mechanism of detoxification is oxidation followed by conjugation.
Bilirubin Di-glucuronide
Meth-hemoglobin is formed during the treatment of cyanide poisoning with sodium nitrite, facilitating the removal of cyanide.
Drugs (prescription), agricultural chemicals, cosmetics, food additives, household chemicals, pollutants/contaminants, and microbial substances.
Biotransformation is not exactly synonymous with detoxification, as metabolites can sometimes be more toxic than the parent substance, a process known as bioactivation or toxication.
Glutathione binds to the substrate through the nucleophilic cysteine group.
The liver detoxifies harmful substances such as alcohol, drugs, and toxins that have entered the bloodstream.
V PAPS (Phospho Adenosyl Phosphate) is involved in the sulfation of aliphatic and aromatic compounds.
The liver plays the most important role in the biotransformation reactions.
Phase I reactions prepare toxins for Phase II reactions by making them more polar, while Phase II reactions further modify these substances for easier excretion.
It is primarily important in the metabolism of endogenous compounds such as 5-hydroxytryptamine.
Sulphanamide (₂HNC₆H₅SO₂NH₂) is an antibiotic that can be acetylated to form Acetyl Sulphanamide.
Phenol
Bilirubin
Phenyl Glucuronide + UDP
Heme-containing enzymes.
Cytochrome P450 containing microsomal enzyme system.
Acetylation involves the reaction of a compound (X) with Acetyl CoA to form Acetyl-X and release CoA-SH.
Xenobiotics can be converted to more toxic metabolites, which can pose additional risks to the body.
Thyroxine, Estrogen, Epinephrine
It exists in multiple forms.
They are usually pharmacologically inactive.
UDPGA formation occurs in the cytosol.
Glycocholic acid
Thio transferase catalyzes the reaction where HCN and Na₂S₂O₃ produce NaSCN and NaHSO₃.
The detoxification of xenobiotics primarily occurs in the liver.
Glucuronic acid is transferred in an activated form as uridine diphosphate glucuronic acid (UDPGA).
It is located in the endoplasmic reticulum (ER) and in many tissues, including the liver.
Phospholipid, specifically Phosphatidyl Choline.
Deoxy glycocholic acid
Cyanide poisoning is treated with sodium nitrite, which pulls cyanide from cytochrome oxidase.
Phase II conjugation reactions use glucuronic acid, glycine, glutathione, sulfation, acetylation, and methylation.
Hippuric acid (excreted in urine)
