scholarly journals Cyclic metabolic pathway of a butylated hydroxytoluene by rat liver microsomal fractions

1974 ◽  
Vol 144 (3) ◽  
pp. 497-501 ◽  
Author(s):  
C Chen ◽  
Y S Shaw

A cyclic metabolic pathway was obtained when 3,5-di-t-butyl-4-hydroxytoluene (BHT) was incubated with a rat liver microsomal preparation. The pathway is as follows: BHT → 4-hydroperoxy-4-methyl-2,6-di-t-butylcyclohexa-2,5-dienone (BHT-OOH) → 4-hydroxy-4-methyl-2,6-di-t-butylcyclohexa-2,5-dienone (BHT-30OH) → BHT. This metabolic pathway suggests that antioxidants such as BHT owe their high efficacy, at least in part, to their metabolic regeneration.

1968 ◽  
Vol 46 (9) ◽  
pp. 1057-1061 ◽  
Author(s):  
G. R. Van Petten ◽  
G. H. Hirsch ◽  
A. D. Cherrington

The drug-metabolizing activity of a 9000 × g supernatant fraction prepared from human placentae obtained immediately after birth was investigated. For comparative purposes a similar rat liver microsomal preparation was used. The metabolism of pentobarbital by oxidation, and of amphetamine by deamination or hydroxylation, proceeded at similar rates in the two tissues. The rate of metabolism of meperidine in the human placental preparation was about two-thirds of that found with the rat liver enzyme. The rate of metabolism of aminopyrine, as determined by measuring the formation of 4-aminoantipyrine or the production of formaldyhyde, was insignificant in the placental preparation, but the metabolism of 4-aminoantipyrine occurred much more rapidly in this tissue than in rat liver. The nitroreductase activity of the human placenta was low; a sixfold activation was achieved by adding a source of glucose 6-phosphate dehydrogenase but the activity was still only one-third of that found in rat liver. The cofactor requirements for the drug-metabolizing enzymes studied were found to be similar in the two tissues. The significance of these findings with respect to the effects of drugs on the mother and the fetus is discussed.


1977 ◽  
Vol 166 (1) ◽  
pp. 17-20 ◽  
Author(s):  
I A F Tavares ◽  
K A Munday ◽  
D C Wilton

1. 4,4′-Dimethylcholesta-7,9,14-trienol is an intermediate in the metabolism of dihydroagnosterol to cholesterol by rat liver homogenate. 2. This triene is reduced by a rat liver microsomal preparation in the presence of NADPH to give 4,4′-dimethylcholesta-7,9-dienol under anaerobic conditions. 3. Reduction of the triene in the presence of [4-3H2]NADPH resulted in the incorporation of 3H into the product. 4. Under aerobic conditions the triene is converted into cholesterol by a rat liver homogenate.


2019 ◽  
Vol 32 (4) ◽  
pp. 261-274 ◽  
Author(s):  
Yuko Ito ◽  
Kota Nakajima ◽  
Yasunori Masubuchi ◽  
Satomi Kikuchi ◽  
Fumiyo Saito ◽  
...  

1990 ◽  
Vol 68 (3) ◽  
pp. 370-373 ◽  
Author(s):  
D. S. Riddick ◽  
J. E. Mackie ◽  
T. E. Massey ◽  
G. S. Marks

Various rat liver cytochrome P-450 (P-450) isozymes are targets for mechanism-based inactivation by 3,5-diethoxycarbonyl-2,6-dimethyl-4-ethyl-1,4-dihydropyridine (4-ethyl DDC). Unlike rat liver, which contains multiple P-450 isozymes, rabbit lung contains only three major isozymes referred to as forms 2, 5, and 6. We have examined the ability of 4-ethyl DDC to destroy P-450 heme in hepatic and pulmonary microsomes from untreated and β-naphthoflavone (βNF)-treated rabbits. This compound destroyed 31% of the P-450 in either hepatic microsomal preparation, but was ineffective at lowering P-450 and heme levels in pulmonary microsomes when examined at a range of concentrations (0.45 – 5.0 mM). These data suggest that rabbit pulmonary P-450 forms 2, 5, and 6 are not targets for destruction by 4-ethyl DDC, despite the ability of this compound to inactivate rat liver P-450c, the orthologue of rabbit lung form 6.Key words: 3,5-diethoxycarbonyl-2,6-dimethyl-4-ethyl-1,4-dihydropyridine, cytochrome P-450, mechanism-based inactivation, rabbit pulmonary microsomes.


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