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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Koop, D. R. Zaphiropoulos, P. G. Porter, T. D. Khani, S. C. Coon, M. J. Fujita, V. S. |
| Abstract | Administration of ethanol to rabbits is known to induce a unique liver microsomal cytochrome P-450, termed isozyme 3a or P-450ALC, which is responsible for the increased oxidation of ethanol and other alcohols and the activation of toxic or carcinogenic compounds such as acetaminophen and N-nitrosodimethylamine. To further characterize this cytochrome P-450 we have identified cDNA clones to isozyme 3a by immunoscreening, DNA hybridization, and hybridization-selection. The cDNA sequence determined from two overlapping clones contains an open reading frame of 1416 nucleotides, and the first 25 amino acids of this reading frame correspond to residues 21-45 of cytochrome P-450 3a. The complete polypeptide, including residues 1 to 20, contains 492 amino acids and has a molecular weight of 56,820. Cytochrome P-450 3a is approximately 55% identical in sequence to P-450 isozymes 1 and 3b and 48% identical to isozyme 2. Hybridization of clone p3a-2 to electrophoretically fractionated rabbit liver poly(A)+ RNA revealed multiple bands, but, with a probe derived from the 3' nontranslated portion of this cDNA, only a 1.9-kilobase band was observed. Treatment of rabbits with imidazole, which increases the content of isozyme 3a, resulted in a transient increase in form 3a mRNA, but this was judged to be insufficient to account for the known 4.5-fold increase in form 3a protein. Genomic DNA analysis indicated that the cytochrome P-450 3a gene does not belong to a large subfamily. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 3 |
| Volume Number | 84 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 1987-03-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Cytochrome P-450 Enzyme System Genetics DNA Ethanol Pharmacology Isoenzymes Microsomes, Liver Metabolism Amino Acid Sequence Animals Cloning, Molecular Biosynthesis DNA Restriction Enzymes Enzyme Induction Genes Drug Effects Nucleic Acid Hybridization Rabbits Research Support, U.S. Gov't, P.H.S. Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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