Identification of multiple constitutive and inducible hepatic cytochrome P450 enzymes in market weight swine.
Constitutive swine enzymes analogous to human/rat cytochrome P450 (CYP) isoforms 1A2, 2A6, 2B1/2/6, 2D6, 2E1, 3A1, and 4A1/3 were detected by Western blot analysis. Swine 2E1 has a molecular weight greater than rat 2E1; swine 2B2 has a molecular weight similar to human 2B6. An induction cocktail containing beta-naphthoflavone, phenobarbital, and dexamethasone induced immunoreactive homologs of 1A1, 1A2, 2B1, 2B2, 3A1, and 3A2. Although the P450 content was increased by induction, there was no difference in the Soret lambda(max). Swine 1A1 has a lower molecular weight than swine 1A2 and rat 1A1. A swine 2B1 homolog was seen after induction, with a molecular weight that was lower than rat 2B1 but higher than swine 2B2. Induction did not augment swine 2B2 levels. The 3A homologs have molecular weights similar to their rodent counterparts. Following induction, swine 3A1 levels increased and were accompanied by the appearance of swine 3A2. Induction had no effect on expression of 2A6, 2B6, 2D6, 2E1, or 4A1/3. Enzyme induction increased the specific activities (nmol/min/mg) of substrates specific for 1A (7 of 7 substrates tested), 2A (2/2), 2B (5/5), 2C (1/3), 2D (3/4), 2E (3/3), 3A (3/5), and 4A (1/1). Although the specific activities of the 2E substrates increased, the turnover number for hydroxylation of chlorzoxazone was unchanged and that of p-nitrophenol and aniline were depressed in induced pigs. These results show that swine CYP isoforms are similar to those identified in human and rodents, but they are also different in many ways.
Myers
M J
MJ
Division of Animal Research, Office of Research, Center for Veterinary Medicine, Food and Drug Administration, Laurel, Maryland 20708, USA. mmyers@cvm.fda.gov
Farrell
D E
DE
Howard
K D
KD
Kawalek
J C
JC
D000818:Animals; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004790:Enzyme Induction; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism*; D008862:Microsomes, Liver / Q000201:enzymology*; D013552:Swine
D007527:Isoenzymes; D003577:Cytochrome P-450 Enzyme System