Specific human CYP 450 isoform metabolism of a pentachlorobiphenyl (PCB-IUPAC# 101).
Polychlorinated biphenyl IUPAC# 101-PCB 101 (chlorination pattern-2,2',4',5,5') is a common, persistent non-coplanar PCB congener found in the ambient environment but information related to its metabolism in humans is lacking. Previous studies indicate PCB 101 is rapidly metabolized in mammals through CYP 2B and 3A family enzymes. Recently, PCB metabolism through a 2A family isoform in hamsters was also reported. To specifically identify the human CYP 450 isoforms responsible for PCB 101 metabolism, we compared human microsome metabolism to metabolism using several specific recombinant human CYP isoforms. These data characterized selective and extensive metabolism by human CYP 2A6. The product formed was the 4-hydroxy-PCB 101 metabolite (4-hydroxy-2,2',4',5,5') and was the only major metabolite observed in the recombinant and human microsome investigation. This is important information for predicting human specific toxicokinetics of PCBs.
McGraw
Joseph E
JE
Department of Biopharmaceutical Sciences, College of Pharmacy, University of Illinois at Chicago, Chicago, IL, USA.
Waller
Donald P
DP
D001189:Aryl Hydrocarbon Hydroxylases / Q000032:analysis / Q000378:metabolism*; D065637:Cytochrome P-450 CYP2A6; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D004785:Environmental Pollutants / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000032:analysis / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000032:analysis / Q000378:metabolism*; D011078:Polychlorinated Biphenyls / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D004785:Environmental Pollutants; D007527:Isoenzymes; D011994:Recombinant Proteins; C009828:2,4,5,2',5'-pentachlorobiphenyl; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6