Detoxification And Biotransformation Of Xenobiotics Ppt To Pdf
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Xenobiotics — foreign substances. Drug metabolism: It is the metabolism of drugs, their biochemical modification or degradation, usually through specialised enzymatic systems. Drug metabolism often converts lipophilic chemical compound into more readily excreted polar products. Drug metabolism : It is the metabolism of drugs, their biochemical modification or degradation, usually through specialised enzymatic systems.
Drug metabolism can result in toxification or detoxification — activation or deactivation of chemical while both can occur, the major metabolites of most drugs are detoxification products. So drug metabolism is a detoxification function the body possesses to defend itself from environment hostility and helps in drug elimination.
Site of drug metabolism : Liver — Primary site, smooth endoplasmic reticulum of liver cell hepatocyte. Contains necessary enzymes. PowerPoint Presentation: Metabolic process may increase or decrease the effects of drugs.
This nomenclature is purely genetic and not functional based. Cytochrome P monooxygenases are located in the endoplasmic reticulum present in liver cells which take part in oxidative biotransformations of xenobiotics. Chemical factors : Insecticides, Carbonmonoxide and other drugs. Diet : Fat free diet will reduce CYP levels as phospholipids become deficient and this is an important component of microsome.
Eg : Imipramine antidepressant acts only after desmethylation to desmethyl imipramine. This conversion is seen only in man and rats whereas in rabbits the 2-hydroxy derivative has been the major metabolite and little antidepressant like activity has been seen. PowerPoint Presentation: Environmental factors : Concommittant drug therapy drugs taken for a long time might induce synthesis of drug metabolising enzymes which might metabolise the drug soon , smoking, alcohol etc.
Physiologic factors : Age, sex, hormones, diseases and pregnancy. Coenzymes do not function properly at an early or young age and also at very old age.
So drug action will be for long time. Sex also influences the drug metabolism as there are different conc. Similarly liver diseases may change drug metabolism. Drugs like barbiturates and benzodiazepines pass from mother to fetus through placenta. Pharmacodynamic factors : Dose , frequency route of administration, tissue metabolism and protein binding might also influence drug metabolism. Significance of Drug metabolism in medicinal chemistry: Significance of Drug metabolism in medicinal chemistry To select and monitor appropriate drug therapy for the patients.
For successful determination of drug regimens ADME. In diseased states the levels of metabolised drug active as well as inactive is important to know as the disease inhibits or expedites the xenobiotics metabolism. Metabolic data info. Oxidation at aliphatic and alicyclic carbon atoms.
Oxidation involving carbon-heteroatom systems Carbon-nitrogen systems aliphatic and aromatic. Carbon-oxygen systems. Carbon — sulphur systems. Oxidation of alcohols and aldehydes Other miscellaneous Oxidation reactions. Reductive and hydrolytic reactions: Reductive and hydrolytic reactions II- Reductive reactions : Reduction of aldehydes and ketones.
Reduction of nitro and azo compounds Miscellaneous reductive reactions. III- Hydrolytic reactions : Hydrolysis of esters and amides Hydrolysis of epoxides and arene oxides by epoxide hydrase. Here oxidation of aromatic compounds arenes to their corresponding phenolic metabolites arenols takes place. These epoxides are readily converted to 1,2-diols in the presence of the enzyme.
Primary alcohol metabolites are further oxidised to aldehydes and carboxylic acids. The antiarrhythmic agent quinidine is metabolised by allylic hydroxylation to 3-hydroxy quinidine which shows significant antiarrythmic activity in animals and possibly in humans. Metabolites from these oxidations are susceptible to further oxidation to yield aldehyde, ketones or carboxylic acids. Oxidations involving carbon-heteroatom systems.
N 2 and O 2 functionalities are commonly found in most of the drugs and foreign compounds. Sulfur functionalities occur occasionally. Metabolic oxidation of carbon-nitrogen, carbon —oxygen and carbon-sulfur systems involves two basic types of biotransformations. PowerPoint Presentation: 2. Tertiary and aliphatic amines: Tertiary and aliphatic amines This drug here undergoes oxidative N- dealkylation. Gour university sagar m. Follow us on:.
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Presentation Transcript. Oxidation of Allylic C-atom:: Oxidation of Allylic C-atom: Microsomal hydroxylation at allylic C-atom is o bserved commonly in drug metabolism. Secondary and Primary amines: Oxidative N-dealkylation, deamination and N-oxidation reactions :: Secondary and Primary amines: Oxidative N- dealkylation , deamination and N-oxidation reactions :. You do not have the permission to view this presentation.
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Xenobiotics causing a variety of toxicity in biological systems could be classified as two types, inorganic and organic chemicals. In the class for toxicology, we have encountered some difficulties in explaining the mechanisms of toxicity caused especially by organic chemicals. Here, a simple flowchart was introduced for explaining the mechanism of toxicity caused by organic xenobiotics, as the central dogma of molecular biology. This flowchart, referred to as a central dogma, was described based on a view of various aspects as follows: direct-acting chemicals vs. Thus, the primary objective of this flowchart is to help better understanding of the organic xenobiotics-induced toxic mechanisms, providing a major pathway for toxicity occurring in biological systems. Toxicology is simply defined as the study of the adverse effects of xenobiotics on living organisms. A xenobiotic is a general term referring to any chemical foreign to an organism or, in other words, any compound not occurring within the normal metabolic pathways of a biological system 1 , 2.
Detoxification or detoxication is a series of biochemical reactions to convert toxic compounds to less toxic and more easily excretable forms. 1. Site of detoxification.
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The Internet Journal of Nutrition and Wellness. Xenobiotics are chemicals found in organisms, but not expected to be produced or present in them; or they are chemicals found in much higher concentrations than usual. There are number of factors which alter the rate of Xenobiotics absorption which include diet, motility of intestine, interference with gastro intestinal flora, changes in the rate of gastric emptying, age, and the dissolution rate.
If your institution subscribes to this resource, and you don't have a MyAccess Profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus. Please consult the latest official manual style if you have any questions regarding the format accuracy. Describe the two general phases of xenobiotic metabolism, the first involving mainly hydroxylation reactions catalyzed by cytochrome P species and the second conjugation reactions catalyzed by various enzymes.
Chronic fatigue, in its various manifestations, frequently co-occur with pain, sleep disturbances and depression and is a non-communicable condition which is rapidly becoming endemic worldwide. However, it is handicapped by a lack of objective definitions and diagnostic measures. This has prompted the World Health Organization to develop an international instrument whose intended purpose is to improve quality of life QOL , with energy and fatigue as one domain of focus. To complement this objective, the interface between detoxification, the exposome, and xenobiotic-sensing by nuclear receptors that mediate induction of biotransformation-linked genes, is stimulating renewed attention to a rational development of strategies to identify the metabolic profiles in complex multifactorial conditions like fatigue.
DETOXIFICATION. 1. Xenos Xenobiotic Compound that is foreign to body Stranger; 2. As part of normal metabolism, body produces toxins.
Transcriptional regulation of xenobiotic detoxification in Drosophila. PubMed Central. Living organisms, from bacteria to humans, display a coordinated transcriptional response to xenobiotic exposure, inducing enzymes and transporters that facilitate detoxification. Several transcription factors have been identified in vertebrates that contribute to this regulatory response. In contrast, little is known about this pathway in insects.
Detoxification or detoxication detox for short  is the physiological or medicinal removal of toxic substances from a living organism , including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period of drug withdrawal during which an organism returns to homeostasis after long-term use of an addictive substance. Many alternative medicine practitioners promote various types of detoxification such as detoxification diets. Scientists have described these as a "waste of time and money". The liver and kidney are naturally capable of detox, as are intracellular specifically, inner membrane of mitochondria or in the endoplasmic reticulum of cells proteins such as CYP enyzmes. In cases of kidney failure , the action of the kidneys is mimicked by dialysis ; kidney and liver transplants are also used for kidney and liver failure, respectively.
If your institution subscribes to this resource, and you don't have a MyAccess Profile, please contact your library's reference desk for information on how to gain access to this resource from off-campus. Please consult the latest official manual style if you have any questions regarding the format accuracy. Biotransformation is the metabolic conversion of endogenous and xenobiotic chemicals to more water-soluble compounds. Xenobiotic biotransformation is accomplished by a limited number of enzymes with broad substrate specificities. Phase I reactions involve hydrolysis, reduction, and oxidation. Phase II biotransformation reactions include glucuronidation, sulfonation more commonly called sulfation , acetylation, methylation, and conjugation with glutathione mercapturic acid synthesis , which usually result in increased hydrophilicity and elimination. Generally, the physical properties of a xenobiotic are changed from those favoring absorption lipophilicity to those favoring excretion in urine or feces hydrophilicity.
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