Metabohzer

Vertical stratification, where the most easily degraded compounds are metabohzed first upon entering the filter bed. The more difficult-to-metabolize compounds pass through the lower region of the bed and are metabolized in the upper levels. 

Halothane remams the leading anesthetic m many parts of the world However, It IS beheved to cause a fuhmnant hepatitis in rare, susceptible mdividuals, especially after repeated use within short intervals It was believed, but now disputed, that this hepatitis resulted from toxic metabohtes [2] (Actually, the major metabolite is tnfluoroacebc acid, which as a salt in body fluids, is benign ) As rare as the hepatitis cases were (1 m 20 000), they frequently resulted m malpractice suits, especially in the United States This problem led to a search for more ideal nonflammable anesthetics that are also metabohzed to a lesser extent [i]... 

Fungal chitin synthases are found as integral proteins of the plasma membrane and in chitosomes a divalent cation, Mg(II), is necessary for enzyme activity but neither primers nor a hpid intermediate are required. The substrate and free GlcNAc activate the allosteric enzyme. UDP, the byproduct of the enzymatic activity, is strongly inhibitory to chitin synthase however, it may be metabohzed readily to UMP by a diphosphatase. 

ADH also has clinical significance in the metabolism of methanol and ethylene glycol, two drugs with toxic metabolites. Methanol is oxidized by ADH to formaldehyde, which damages the retina and can cause blindness. Ethylene glycol is metabohzed by ADH to oxalic acid, which has renal tox-... 

For recreational use, ketamine is often snorted or smoked with marijuana or tobacco products, but it may also be injected intramuscularly (Weiner et al. 2000). The typical street dose of ketamine ranges from 30 to 300 mg. These amounts are in contrast to the chnical doses used for anesthesia, which range from 2 to 10 mg/kg. Ketamine has a half-life of less than 2 hours and is metabohzed by the cytochrome P450 en2yme system (Koesters et al. 2002 Reich and SUvay 1989). 

The nature of the diet sets the basic pattern of metabohsm. There is a need to process the products of digestion of dietary carbohydrate, lipid, and protein. These are mainly glucose, fatty acids and glycerol, and amino acids, respectively. In ruminants (and to a lesser extent in other herbivores), dietary cellulose is fermented by symbiotic microorganisms to short-chain fatty acids (acetic, propionic, butyric), and metabohsm in these animals is adapted to use these fatty acids as major substrates. All the products of digestion are metabohzed to a common product, acetyl-CoA, which is then oxidized by the citric acid cycle (Figure 15-1). 

Testosterone is metaboHzed by two pathways. One involves oxidation at the 17 position, and the other involves reduction of the A ring double bond and the 3-ketone. Metabohsm by the first pathway occurs in many tissues, including liver, and produces 17-ketosteroids that... 

Another example of enzyme induction involves CYP2E1, which is induced by consumption of ethanol. This is a matter for concern, because this P450 metabohzes certain widely used solvents and also components found in tobacco smoke, many of which are established carcinogens. Thus, if the activity of CYP2E1 is elevated by induction, this may increase the risk of carcinogenicity developing from exposure to such compounds. 

Again, this can affect the doses of certain dmgs that are administered to patients. Various diseases (eg, cirrhosis of the liver) can affect the activities of drug-metabohz-ing enzymes, sometimes necessitating adjustment of dosages of various drugs for patients with these disorders. 

Hume clan ts. Low molecular weight materials such as glycerol and sorbitol are included in some products to reduce water loss and are usually readily metabohzed unless present in high concentrations (see section 1.3.3). 

GUO Z, SMITH T J, WANG E, SADRIEH N, MA Q, THOMAS P E and YANG C S (1992) Effects of phenethyl isothiocyanate, a carcinogenesis inhibitor, on xenobiotic-metabohzing enzymes and nitrosamine metabolism in rats . Carcinogenesis, 13 2205-10. 

In animals, the major function of carotenoids is as a precursor to the formation of vitamin A. Carotenoids with provitamin A activity are essential components of the human diet, and there is considerable evidence that they are absorbed through the diet and often metabohzed into other compounds. Beyond their important role as a source of vitamin A for humans, dietary carotenoids, including those that are not provitamin A carotenoids, have been implicated as protecting against certain forms of cancer and cardiovascular disease. ... 

Graf, BA, C Ameho, GG Doinikowski, PE Mibury, CY Chen, and JB Blumberg. 2006. Rat gestrointestinal tissues metabohze quercetin. JNutr 136(l) 39-44. 

In the presence of the inhihitor rotenone (to prevent the oxidation of NADH hy the electron transport chain), succinate can be metabohzed only to fumarate, producing an FADH2 in the process. 

Gene Polymorphic variant Extensive metabohzers (%) Intermediate metabohzers (%) Poor metabohzers (%) Ultrarapid metabohzers (%)... 

Shin HY et al (2003) Purification and characterization of a a-L-arabinopyranosidase and a-L-arabinofuranosidase from Bifidobacterium breve K-110, a human intestinal anaerobic bacterium metabolizing ginsenoside Rb2 and Rc. Appl Environ Microbiol 69 7116 Park SY et al (2001) Purification and characterization of ginsenoside Rbi-metabohzing P-glucosidase from Fusobacterium K-60, a human intestinal anaerobic bacterium. Biosci Biotechnol Biochem 65(5) 1163... 

First pass metabolism (metabohsm in the intestinal wall or by the fiver before the substance reaches the systemic circulation) can also be a cause for nontoxicity, which can be route- and species-dependent. Information about which metabohtes, and the relative quantities thereof, are formed, is important. Chemical substances are metabohzed to metabohtes, which may be toxicol-ogically more or less active than the parent compound, and the relative quantity of the metabolites may differ greatly among animal species. If it is known that toxicity is related to formation of an active metabolite, knowledge about the amount of this particular metabolite in humans and test animals is very important for the hazard assessment. If humans do not form the toxic metabohte, the hazard can be considered limited and vice versa. 

Any biologically produced molecular entity or species having substituents derived from different origins or pathways. For example, glutathione reacts with many arene oxides, and the bioconjugate product is then processed for excretion. Bioconjugates are often more water-soluble, and they are typically more readily com-partmentahzed and/or metabohzed. 

Aromatase inhibitors may be classified into two types. Type 1 aromatase inhibitors bind to the aromatase enzyme irreversibly, so they are called inactivators. In some cases they are dubbed mechanism-based or suicide inhibitors when they are metabolized by the enzyme into reactive intermediates that bind covalently to the active site. Type 1 aromatase inhibitors are usually steroidal in structure as represented by exemestane (1), formestane (13), and atamestane (14). Formestane (13) was launched by Ciba-Geigy in 1992. As formestane (13) is readily and extensively metabohzed when administered orally, it is used as a depot formulation for injection. 

Goldstein JA, Ishizaki T, Chiba K, et al (1997) Frequencies of the defective CYP2C19 ahe-les responsible for the mephenytoin poor metabohzer phenotype in various Oriental, Caucasian, Saudi Arabian and American black populations. Pharmacogenetics 7 59-64 Greenberg BD, McMahon FJ, Murphy DL (1998) Serotonin transporter candidate gene studies in affective disorders and personality promises and potential pitfahs [guest editorial]. Mol Psychiatry 3 186-189... 

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