Inhibition of purified rabbit muscle phosphorylase a and phosphorylase b by polychlorinated biphenyls, polychlorinated biphenylols and polybrominated biphenyls.
Polychlorinated biphenyls, polychlorinated biphenylols and polybrominated biphenyls inhibited both rabbit muscle phosphorylase a and phosphorylase b (1,4-alpha-D-glucan:orthophosphate alpha-d-glucosyltransferase, EC 2.4.1.1). The degree of inhibition was dependent upon the relative hydrophobicity of the compounds and steric hinderance. 2,4,5,2',4',5'-Hexabromobiphenyl and Firemaster BP-6 were the most effective inhibitors (Ki, 15 . 10(-6) M). Phosphorylase b was inhibited by compounds of all three groups. 2,4,5,2',4',5'-Hexachlorobiphenyl and 2,4,5,2',4',5'-hexabromobiphenyl did not significantly inhibit phosphorylase a. All of the compounds inhibited phosphorylase a less than phosphorylase b, except 2',3',4',5,5'-pentachloro-2-biphenylol, which was equally effective on each enzyme. Kinetic analysis showed the inhibition was non-competitive and mixed. The results indicate that the compounds bind to hydrophobic site(s) on phosphorylase, access to which is limited by phosphorylation of serine 24.
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009132:Muscles / Q000201:enzymology*; D010762:Phosphorylase a / Q000037:antagonists & inhibitors*; D010763:Phosphorylase b / Q000037:antagonists & inhibitors*; D006005:Phosphorylases / Q000037:antagonists & inhibitors*; D011075:Polybrominated Biphenyls / Q000494:pharmacology*; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D011817:Rabbits
D001713:Biphenyl Compounds; D011075:Polybrominated Biphenyls; C034133:2',3',4',5,5'-pentachloro-2-biphenylol; C018566:2,4,5,2',4',5'-hexabromobiphenyl; D011078:Polychlorinated Biphenyls; D010762:Phosphorylase a; D010763:Phosphorylase b; D006005:Phosphorylases