Multiplicity strain differences, and topology of phenobarbital-induced cytochromes P-450 in rat liver microsomes. 1982

G P Vlasuk, and J Ghrayeb, and D E Ryan, and L Reik, and P E Thomas, and W Levin, and F G Walz

The multiplicity of phenobarbital-induced cytochromes P-450 in live microsomes from male rats was investigated by using two-dimensional gel electrophoresis, peptide fingerprinting, and immunoaffinity chromatography. Two colonies each of Holtzman and Long-Evans rats were studied. Four molecular forms of phenobarbital-induced cytochromes P-450 were distinguished as polypeptides (designated PB3, variant PB3, PB4, and PB5) which showed apparent immunochemical identity and greater than or equal to 95% fingerprint homology. Two of these polypeptides corresponded to cytochrome P-450b [Ryan, D., Thomas, P. E., Korzeniowski, D., & Levin, W. (1979) J. Biol. Chem. 254, 1365-1374] and cytochrome P-450e [Ryan, D., & Levin, W. (1981) Fed. Proc., Fed. Am. Soc. Exp. Biol. 40, 1640] which had been purified from Long-Evans rats (variant PB3 and PB5, respectively). Each rat colony was characterized by unique combinations of two or three of these immunochemically related forms of cytochromes P-450. Cytochrome P-450e was present in rats from all four colonies, but cytochrome P-450b was only found in Long-Evans rats. Polypeptide PB3 was only found in the two colonies of Holtzman rats, whereas polypeptide PB4 was present in one colony each of Holtzman and Long-Evans rats. In addition to these forms of cytochrome P-450, rats from each colony also evidenced three other major phenobarbital-induced polypeptides which gave unique fingerprints, and one of these was identified as representing epoxide hydrolase. Proteolytic digestion studies of intact microsomes demonstrated that the four immunochemically identical forms of cytochrome P-450 were partially exposed on the outer (cytoplasmic) surface of microsomes. However, polypeptide PB3 was characterized by the greatest rate of proteolytic degradation. These results clearly demonstrate that phenobarbital-induced cytochromes P-450 include microheterogeneous proteins which show remarkable variations related to rat strains and/or colony.

UI MeSH Term Description Entries
D007120 Immunochemistry Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies.
D008297 Male Males
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
D010446 Peptide Fragments Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques. Peptide Fragment,Fragment, Peptide,Fragments, Peptide
D010447 Peptide Hydrolases Hydrolases that specifically cleave the peptide bonds found in PROTEINS and PEPTIDES. Examples of sub-subclasses for this group include EXOPEPTIDASES and ENDOPEPTIDASES. Peptidase,Peptidases,Peptide Hydrolase,Protease,Proteases,Proteinase,Proteinases,Proteolytic Enzyme,Proteolytic Enzymes,Esteroproteases,Enzyme, Proteolytic,Hydrolase, Peptide
D010634 Phenobarbital A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations. Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
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
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
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D013045 Species Specificity The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species. Species Specificities,Specificities, Species,Specificity, Species

Related Publications

G P Vlasuk, and J Ghrayeb, and D E Ryan, and L Reik, and P E Thomas, and W Levin, and F G Walz
May 1988, Archives of biochemistry and biophysics,
G P Vlasuk, and J Ghrayeb, and D E Ryan, and L Reik, and P E Thomas, and W Levin, and F G Walz
October 1983, The Biochemical journal,
G P Vlasuk, and J Ghrayeb, and D E Ryan, and L Reik, and P E Thomas, and W Levin, and F G Walz
March 1989, The Journal of biological chemistry,
G P Vlasuk, and J Ghrayeb, and D E Ryan, and L Reik, and P E Thomas, and W Levin, and F G Walz
February 1972, Biochemical and biophysical research communications,
G P Vlasuk, and J Ghrayeb, and D E Ryan, and L Reik, and P E Thomas, and W Levin, and F G Walz
July 1975, The Journal of biological chemistry,
G P Vlasuk, and J Ghrayeb, and D E Ryan, and L Reik, and P E Thomas, and W Levin, and F G Walz
January 1969, Clinical pharmacology and therapeutics,
G P Vlasuk, and J Ghrayeb, and D E Ryan, and L Reik, and P E Thomas, and W Levin, and F G Walz
January 1973, Drug metabolism and disposition: the biological fate of chemicals,
G P Vlasuk, and J Ghrayeb, and D E Ryan, and L Reik, and P E Thomas, and W Levin, and F G Walz
January 1977, General pharmacology,
G P Vlasuk, and J Ghrayeb, and D E Ryan, and L Reik, and P E Thomas, and W Levin, and F G Walz
December 1972, Archives of biochemistry and biophysics,
G P Vlasuk, and J Ghrayeb, and D E Ryan, and L Reik, and P E Thomas, and W Levin, and F G Walz
December 1984, European journal of biochemistry,
Copied contents to your clipboard!