Microsomal metabolism of carbon tetrachloride: participation of pyridine nucleotide synergism.
The role of pyridine nucleotide synergism in CCl4 metabolism was evaluated for its potential contribution to enhanced lipid peroxidation. Male Sprague-Dawley rats receiving either no treatment (control) or treatment with phenobarbital (PB) were used to prepare hepatic microsomes. Metabolism was evaluated in the presence and absence of an NADPH generator system and in the presence and absence of NADH. The generator system produced a greater extent of metabolism for both control and PB microsomes. NADH-catalyzed CCl4 metabolism occurred to a similar extent in control and PB microsomes, amounting to 9-10% and 5-6% of the NADPH rate in control and PB microsomes, respectively. Synergism by NADH occurred at the lowest concentrations of NADPH, apparently decreasing the Km for NADPH and having little effect on the Vmax. Addition of NAD+ produced synergism, as did the addition of 5' AMP, an inhibitor of nucleotide pyrophosphatase. Thus, the synergistic increase in CCl4 metabolism produced by NADH may occur in part from an increased availability of NADPH, as a result of decreased degradation, rather than by electron donation from NADH.
Tortoriello
P
P
Department of Pharmacology and Nutrition, University of Southern California, School of Medicine, Los Angeles 90033.
Advani
S V
SV
Riebow
J F
JF
Bidlack
W R
WR
D000818:Animals; D002251:Carbon Tetrachloride / Q000378:metabolism*; D066298:In Vitro Techniques; D015227:Lipid Peroxidation; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D009249:NADP / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D011725:Pyridines / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D011725:Pyridines; D009243:NAD; D009249:NADP; D002251:Carbon Tetrachloride; D010634:Phenobarbital