Oxidative defluorination of 1,1,1,2-tetrafluoroethane by rat liver microsomes.
1,1,1,2-Tetrafluoroethane (R-134a) is a non-ozone-depleting alternative to dichlorodifluoromethane for use as an air-conditioning refrigerant and as a propellant in anti-asthmatic and other pharmaceutical preparations. Hepatic microsomes, supplemented with NADPH, catalyzed the release of F- from R-134a; metabolite production was positively correlated with both duration of incubation and gas phase [R-134a]. Defluorination of R-134a was inhibited by CO, lack of NADPH, or heat denaturation of microsomes. Release of F- from R- 134a biotransformation as shown by the near-total lack of dehalogenation during anaerobic incubations. R-134a did not produce a difference spectrum (360 to 500 nm) with either oxidized or dithionite-reduced microsomes. Microsomes from phenobarbital- or Aroclor 1254-treated rats produced greater amounts of F- per mg protein from high concentrations of R-134a than did microsomes from untreated rats, but when normalized for microsomal cytochrome P-450 content both phenobarbital and Aroclor treatment decreased the specific activity (nmol F-/nmol cytochrome P-450) of R-134a metabolism. Furthermore, while defluorination of R-134a by microsomes from livers of untreated rats was substrate-saturable (Vmax, 11 nmol of F-/nmol cytochrome P-450/15 min; KM, 8% R-134a), R-134a dehalogenation by microsomes from Aroclor-treated rats was nonsaturable with [R-134a] as high as 69%. Microsomes from phenobarbital-treated rats retained the saturable, low KM activity, but also exhibited the apparently nonsaturable kinetic component when [R-134a] was greater than 24%.(ABSTRACT TRUNCATED AT 250 WORDS)
Olson
M J
MJ
Biomedical Science Department, General Motors Research Labs., Warren, MI 48090.
Reidy
C A
CA
Johnson
J T
JT
Pederson
T C
TC
D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001386:Azides / Q000494:pharmacology; D001711:Biotransformation; D020111:Chlorodiphenyl (54% Chlorine); D005459:Fluorides / Q000032:analysis / Q000378:metabolism*; D005561:Formates / Q000494:pharmacology; D006221:Halothane / Q000378:metabolism; D006845:Hydrocarbons, Fluorinated / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010634:Phenobarbital / Q000494:pharmacology; D011199:Potentiometry; D051381:Rats; D011916:Rats, Inbred F344; D013053:Spectrophotometry; D004980:Ethane / Q000031:analogs & derivatives; D005466:Fluorocarbons
D001140:Aroclors; D001386:Azides; D020111:Chlorodiphenyl (54% Chlorine); D005459:Fluorides; D005561:Formates; D006221:Halothane; D006845:Hydrocarbons, Fluorinated; D010634:Phenobarbital; C063006:norflurane; D004980:Ethane; D005466:Fluorocarbons