scholarly journals Loss of haem from cytochrome P-450 caused by lipid peroxidation and 2-allyl-2-isoprophylacetamide. An abnormal pathway not involving production of carbon monoxide

1977 ◽  
Vol 168 (3) ◽  
pp. 417-422 ◽  
Author(s):  
F De Matteis ◽  
A H Gibbs ◽  
A Unseld
Keyword(s):  
Lipid Peroxidation ◽  
Carbon Monoxide ◽  
Significant Extent ◽  
Haem Oxygenase ◽  
Bridge Carbon ◽  
Cytochrome P 450

1. Microsomal preparations undergoing lipid peroxidation produce CO and lose haem from cytochrome P-450. 2. The amount of CO produced does not correlate with the amount of haem lost and, after pre-labelling of microsomal haem in its bridges with 5-amino[5-14C]laevulinate, the radioactivity lost from haem is not recorved as CO. 3. Similarly, when pre-labelled microsomal haem is destroyed by the action of 2-allyl-2-isopropylacetamide, no radioactivity is recovered as CO. In clear contrast, on degradation of haem by the haem oxygenase system, CO is produced in an amount equimolar to the haem lost. 4. It is concluded that (a) the CO produced during lipid peroxidation originates from a source different from haem and (b) the degradations of haem caused by lipid peroxidation and 2-allyl-2-isopropylacetamide do not involve to any significant extent evolution of the methene-bridge carbon of haem as CO.

scholarly journals Degradation of cytochrome P-450 haem by carbon tetrachloride and 2-allyl-2-isopropylacetamide in rat liver in vivo and in vitro. Involvement of non-carbon monoxide-forming mechanisms

1979 ◽  
Vol 184 (3) ◽  
pp. 481-489 ◽  
Author(s):  
Philip S. Guzelian ◽  
Robert W. Swisher
Keyword(s):  
Lipid Peroxidation ◽  
Free Radicals ◽  
Carbon Tetrachloride ◽  
Pulse Labelling ◽  
Forming Mechanism ◽  
Oxygenase Activity ◽  
Haem Oxygenase ◽  
Cytochrome P 450

Degradation of intrinsic hepatic [14C]haem was analysed as 14CO formation in living rats and in hepatic microsomal fractions prepared from these animals 16h after pulse-labelling with 5-amino[5-14C]laevulinic acid, a precursor that labels bridge carbons of haem in non-erythroid tissues. NADPH-catalysed peroxidation of microsomal lipids in vitro (measured as malondialdehyde) was accompanied by loss of cytochrome P-450 and microsome-associated [14C]haem (largely cytochrome P-450 haem), but little 14CO formation. No additional 14CO was formed when carbon tetrachloride and 2-allyl-2-isopropylacetamide were added to stimulate lipid peroxidation and increase loss of cytochrome P-450 [14C]haem. Because the latter effect persisted despite inhibition of lipid peroxidation with MnCl2 or phenyl-t-butylnitrone(a spin-trapping agent for free radicals), it was concluded that carbon tetrachloride, as reported for 2-allyl-2-isopropylacetamide, may promote loss of cytochrome P-450 haem through a non-CO-forming mechanism independent of lipid peroxidation. By comparison with breakdown of intrinsic haem, catabolism of [14C]methaemalbumin by microsomal haem oxygenase in vitro produced equimolar quantities of 14CO and bilirubin, although these catabolites reflected only 18% of the degraded [14C]haem. This value was increased to 100% by addition of MnCl2, which suggests that lipid peroxidation may be involved in degradation of exogenous haem to products other than CO. Phenyl-t-butylnitrone completely blocked haem oxygenase activity, which suggests that hydroxy free radicals may represent a species of active oxygen used by this enzyme system. After administration of carbon tetrachloride or 2-allyl-2-isopropylacetamide to labelled rats, hepatic [14C]haem was decreased and haem oxygenase activity was unchanged; however, 14CO excretion was either unchanged (carbon tetrachloride) or decreased (2-allyl-2-isopropylacetamide). These changes were unaffected by cycloheximide pretreatment. From the lack of parallel losses of cytochrome P-450 [14C]haem and 14CO excretion, one may infer that an important fraction of hepatic [14C]haem in normal rats is degraded by endogenous pathways not involving CO. We conclude that carbon tetrachloride and 2-allyl-2-isopropylacetamide accelerate catabolism of cytochrome P-450 haem through mechanisms that do not yield CO as an end product, and that are insensitive to cycloheximide and independent of haem oxygenase activity.

Oxygenation of 18-hydroxycorticosterone as the final reaction for aldosterone biosynthesis

1984 ◽  
Vol 107 (3) ◽  
pp. 395-400 ◽  
Author(s):  
Itaru Kojima ◽  
Etsuro Ogata ◽  
Hiroshi Inano ◽  
Bun-ichi Tamaoki
Keyword(s):  
Carbon Monoxide ◽  
Hydroxysteroid Dehydrogenase ◽  
Dependent Manner ◽  
In Vitro Production ◽  
Mitochondrial Preparation ◽  
Final Reaction ◽  
Vitro Production ◽  
Dose Dependent ◽  
Cytochrome P 450

Abstract. Incubation of 18-hydroxycorticosterone with the sonicated mitochondrial preparation of bovine adrenal glomerulosa tissue leads to the production of aldosterone, as measured by radioimmunoassay. The in vitro production of aldosterone from 18-hydroxycorticosterone requires both molecular oxygen and NADPH, and is inhibited by carbon monoxide. Cytochrome P-450 inhibitors such as metyrapone, SU 8000. SU 10603, SKF 525A, amphenone B and spironolactone decrease the biosynthesis of aldosterone from 18-hydroxycorticosterone. These results support the conclusion that the final reaction in aldosterone synthesis from 18-hydroxycorticosterone is catalyzed by an oxygenase, but not by 18-hydroxysteroid dehydrogenase. By the same preparation, the production of [3H]aldosterone but not [3H]18-hydroxycorticosterone from [1,2-3H ]corticosterone is decreased in a dose-dependent manner by addition of non-radioactive 18-hydroxycorticosterone.

SOME CHEMICAL PROPERTIES OF CYTOCHROME P-450 AND ITS CARBON MONOXIDE COMPOUND (P-450.CO)

1970 ◽  
Vol 174 (1 Biological Ef) ◽  
pp. 205-217 ◽  
Author(s):  
David Y. Cooper ◽  
Heinz Schleyer ◽  
Dr. rer. Nat ◽  
Otto Rosenthal
Keyword(s):  
Carbon Monoxide ◽  
Chemical Properties ◽  
Cytochrome P 450

scholarly journals Regulation of hepatic haem metabolism. Disparate mechanisms of induction of haem oxygenase by drugs and metals

1988 ◽  
Vol 250 (1) ◽  
pp. 189-196 ◽  
Author(s):  
B C Lincoln ◽  
J F Healey ◽  
H L Bonkovsky
Keyword(s):  
Chick Embryo ◽  
Primary Culture ◽  
In Ovo ◽  
Oxygenase Activity ◽  
Haem Oxygenase ◽  
Cytochrome P 450

We studied drug- and metal-mediated increases in activity of haem oxygenase, the rate-controlling enzyme for haem breakdown, in chick-embryo hepatocytes in ovo and in primary culture. Phenobarbitone and phenobarbitone-like drugs (glutethimide, mephenytoin), which are known to increase concentrations of an isoform of cytochrome P-450 in chick-embryo hepatocytes, were found to increase activities of haem oxygenase as well. In contrast, 20-methylcholanthrene, which increases the concentration of a different isoform of cytochrome P-450, had no effect on activity of haem oxygenase. Inhibitors of haem synthesis, 4,6-dioxoheptanoic acid or desferrioxamine, prevented drug-mediated induction of both cytochrome P-450 and haem oxygenase in embryo hepatocytes in ovo or in culture. Addition of haem restored induction of both enzymes. These results are interpreted to indicate that phenobarbitone and its congeners induce haem oxygenase by increasing hepatic haem formation. In contrast, increases in haem oxygenase activity by metals such as cobalt, cadmium and iron were not dependent on increased haem synthesis and were not inhibited by 4,6-dioxoheptanoic acid. We conclude that (1) induction of hepatic haem oxygenase activity by phenobarbitone-type drugs is due to increased haem formation, and (2) induction of haem oxygenase by drugs and metals occurs by different mechanisms.

scholarly journals Bariatric Surgery-Induced Weight Loss Reduces Hepatic Lipid Peroxidation Levels and Affects Hepatic Cytochrome P-450 Protein Content

2010 ◽  
Vol 251 (6) ◽  
pp. 1041-1048 ◽  
Author(s):  
Lauren N. Bell ◽  
Constance J. Temm ◽  
Rashmil Saxena ◽  
Raj Vuppalanchi ◽  
Philip Schauer ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Lipid Peroxidation ◽  
Weight Loss ◽  
Protein Content ◽  
Hepatic Lipid ◽  
Hepatic Lipid Peroxidation ◽  
Cytochrome P 450 ◽  
Hepatic Cytochrome
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