Biomaterial Database

The hepatic microsomal mixed-function oxygenase (MFO) system of Alligator mississippiensis: induction by 3-methylcholanthrene (MC). 1989

C S Jewell, and L E Cummings, and M J Ronis, and G W Winston

Institute for Environmental Studies, Louisiana State University, Baton Rouge 70803.

1. Pretreatment of alligators i.p. with 3-methylcholanthrene (MC) resulted in a 1.6-fold increase (P less than 0.001) in cytochrome P-450 specific content and a bathochromic shift in the absorption maximum of reduced, CO-liganded microsomes (448 nm). 2. Control and MC microsomal cytochrome P-450 binding spectra with a number of type I and type II ligands were similar. 3. MC treatment of alligators resulted in a 12-fold increase in benzo[a]pyrene hydroxylase activity, which was inhibited 82% by 0.1 mM alpha-naphthoflavone. The turnover number (units/nmol P-450) of aminopyrine N-demethylase and 7-ethoxycoumarin O-deethylase were unaffected by MC treatment. 4. The O-dealkylation (OD) of a series of alkoxyresorufins (ethoxyresorufin (ER), methoxyresorufin (MR), benzyloxyresorufin (BR), and pentoxyresorufin (PR] was investigated. MC treatment resulted in a significant (P less than 0.001) increase in turnover number of EROD, MROD, and BROD over control values. The turnover number of PROD was unaltered by MC treatment. 5. Western blots showed that control alligator microsomes contain a protein band of lower mol. wt. than either rat cytochrome P-450c (P450 IA1) or P-450d (P450 IA2), which was recognized by antibodies to both P-450c and P-450d but preferentially by that against P-450c. This protein band was induced 3-4-fold by MC. MC treatment induced a second protein band in alligator microsomes of the same mol. wt. as rat P-450d, recognized preferentially by antibodies to rat cytochrome P-450d. 6. These results illustrate that the alligator mixed-function oxidase (MFO) system responds to MC in a similar manner as described in mammals, i.e. induction in P-450 content, increases in specific MFO activities, and the apparent expression of different P-450 isoenzymes.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D008748	Methylcholanthrene	A carcinogen that is often used in experimental cancer studies.	20-Methylcholanthrene,3-Methylcholanthrene,20 Methylcholanthrene,3 Methylcholanthrene
D008862	Microsomes, Liver	Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough.	Liver Microsomes,Liver Microsome,Microsome, Liver
D012016	Reference Values	The range or frequency distribution of a measurement in a population (of organisms, organs or things) that has not been selected for the presence of disease or abnormality.	Normal Range,Normal Values,Reference Ranges,Normal Ranges,Normal Value,Range, Normal,Range, Reference,Ranges, Normal,Ranges, Reference,Reference Range,Reference Value,Value, Normal,Value, Reference,Values, Normal,Values, Reference
D012104	Reptiles	Cold-blooded, air-breathing VERTEBRATES belonging to the class Reptilia, usually covered with external scales or bony plates.	Reptilia,Reptile
D003577	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.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D003579	Cytochrome Reductases		Reductases, Cytochrome
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D006899	Mixed Function Oxygenases	Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.	Hydroxylase,Hydroxylases,Mixed Function Oxidase,Mixed Function Oxygenase,Monooxygenase,Monooxygenases,Mixed Function Oxidases,Function Oxidase, Mixed,Function Oxygenase, Mixed,Oxidase, Mixed Function,Oxidases, Mixed Function,Oxygenase, Mixed Function,Oxygenases, Mixed Function
D000489	Alligators and Crocodiles	Large, long-tailed reptiles, including caimans, of the order Loricata.	Caimans,Crocodiles,Alligators,Caymans,Alligator,Caiman,Cayman,Crocodile,Crocodiles and Alligators