Thymol
Metabolic Detoxication, Drug
Metabolic Detoxication, Phase I
Functionalization of exogenous substances to prepare them for conjugation in PHASE II DETOXIFICATION. Phase I enzymes include CYTOCHROME P450 enzymes and some OXIDOREDUCTASES. Excess induction of phase I over phase II detoxification leads to higher levels of FREE RADICALS that can induce CANCER and other cell damage. Induction or antagonism of phase I detoxication is the basis of a number of DRUG INTERACTIONS.
Metabolic Detoxication, Phase II
The conjugation of exogenous substances with various hydrophilic substituents to form water soluble products that are excretable in URINE. Phase II modifications include GLUTATHIONE conjugation; ACYLATION; and AMINATION. Phase II enzymes include GLUTATHIONE TRANSFERASE and GLUCURONOSYLTRANSFERASE. In a sense these reactions detoxify phase I reaction products.
Glutathione Transferase
A transferase that catalyzes the addition of aliphatic, aromatic, or heterocyclic FREE RADICALS as well as EPOXIDES and arene oxides to GLUTATHIONE. Addition takes place at the SULFUR. It also catalyzes the reduction of polyol nitrate by glutathione to polyol and nitrite.
Psychoses, Alcoholic
Biotransformation
The chemical alteration of an exogenous substance by or in a biological system. The alteration may inactivate the compound or it may result in the production of an active metabolite of an inactive parent compound. The alterations may be divided into METABOLIC DETOXICATION, PHASE I and METABOLIC DETOXICATION, PHASE II.
Aristolochic Acids
Nitro-phenanthrenes occurring in ARISTOLOCHIACEAE and other plants. They derive from stephanine (APORPHINES) by oxidative ring cleavage. The nitro group is a reactive alkylator (ALKYLATING AGENTS) that binds to biological macromolecules. Ingestion by humans is associated with nephropathy (NEPHRITIS). There is no relationship to the similar named aristolochene (SESQUITERPENES).
Aflatoxin B1
A potent hepatotoxic and hepatocarcinogenic mycotoxin produced by the Aspergillus flavus group of fungi. It is also mutagenic, teratogenic, and causes immunosuppression in animals. It is found as a contaminant in peanuts, cottonseed meal, corn, and other grains. The mycotoxin requires epoxidation to aflatoxin B1 2,3-oxide for activation. Microsomal monooxygenases biotransform the toxin to the less toxic metabolites aflatoxin M1 and Q1.
Cytochrome P-450 CYP1A1
A liver microsomal cytochrome P-450 monooxygenase capable of biotransforming xenobiotics such as polycyclic hydrocarbons and halogenated aromatic hydrocarbons into carcinogenic or mutagenic compounds. They have been found in mammals and fish. This enzyme, encoded by CYP1A1 gene, can be measured by using ethoxyresorufin as a substrate for the ethoxyresorufin O-deethylase activity.
Carcinogens
NAD(P)H Dehydrogenase (Quinone)
A flavoprotein that reversibly catalyzes the oxidation of NADH or NADPH by various quinones and oxidation-reduction dyes. The enzyme is inhibited by dicoumarol, capsaicin, and caffeine.
Benzo(a)pyrene
Glutathione
DNA Adducts
Anticarcinogenic Agents
Glucosinolates
Cytochrome P-450 Enzyme System
A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.
Carboxylesterase
Carboxylesterase is a serine-dependent esterase with wide substrate specificity. The enzyme is involved in the detoxification of XENOBIOTICS and the activation of ester and of amide PRODRUGS.
Liver
Cytochrome P-450 CYP1A2
Enzyme Induction
Carboxylic Ester Hydrolases
Microsomes, Liver
Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.
Oxidation-Reduction
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).