Multiple forms of cytochrome P-450 related to forms induced marginally by phenobarbital. Differences in structure and in the metabolism of alkoxyresorufins.
The properties of five structurally related forms of cytochrome P-450 (PB1a, PB1b, PB2a, PB2b and PB2d) isolated from rats treated with phenobarbital have been compared with two forms isolated previously now termed 'PB1c' and 'PB2c'. These enzymes were characterized by their marginal inducibility by phenobarbital and are clearly distinguishable from the major phenobarbital-inducible proteins. PB1a and PB1b differed in Mr (52,700 and 52,900), absorption spectra and papain-proteolysis fragments. However, they had identical N-terminal sequences. PB2a, PB2b and PB2d had apparent Mr values of 52,900, 52,900 and 50,800. PB2a and PB2b had different N-terminal sequences and, after digestion with papain, gave different papain-proteolysis fragments. The N-terminal sequence of PB2b was similar to, but not identical with, that of pregnenolone-16 alpha-carbonitrile-inducible P-450 species, and PB2b was the protein most closely related to PB2c. The extent of immunocross-reactivity among the forms was stronger within, than between, the PB1 and PB2 groups. Even structurally similar forms were functionally diverse, exhibiting large differences in metabolic specificity in the dealkylation of a series of alkoxyresorufins.
D000595:Amino Acid Sequence; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D004790:Enzyme Induction / Q000187:drug effects; D004987:Ethers / Q000378:metabolism; D007527:Isoenzymes / Q000302:isolation & purification / Q000378:metabolism*; D008297:Male; D010078:Oxazines / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013053:Spectrophotometry; D013379:Substrate Specificity
D004987:Ethers; D007527:Isoenzymes; D010078:Oxazines; C014180:resorufin; D003577:Cytochrome P-450 Enzyme System; D010634:Phenobarbital