scholarly journals Cobalt stimulation of heme degradation in the liver. Dissociation of microsomal oxidation of heme from cytochrome P-450

1975 ◽  
Vol 250 (11) ◽  
pp. 4171-4177
Author(s):  
MD Maines ◽  
A Kappas
Keyword(s):  
Microsomal Oxidation ◽  
Heme Degradation ◽  
Cytochrome P 450 ◽  
Stimulation Of

Renal cytochrome P-450-arachidonic acid metabolism: localization and hormonal regulation in SHR

1992 ◽  
Vol 262 (4) ◽  
pp. F591-F599 ◽  
Author(s):  
K. Omata ◽  
N. G. Abraham ◽  
M. L. Schwartzman
Keyword(s):  
Hormonal Regulation ◽  
Distribution Patterns ◽  
Arachidonic Acid Metabolism ◽  
Proximal Tubules ◽  
Ang Ii ◽  
Spontaneously Hypertensive ◽  
Nephron Segments ◽  
Wistar Kyoto ◽  
Cytochrome P 450 ◽  
Stimulation Of

Epoxygenase and omega- and omega-1-hydroxylases are the major cytochrome P-450-arachidonate (P-450-AA) metabolizing enzymes in renal tissues. We measured P-450-AA metabolism in single nephron segments and determined the tubular localization of this activity in spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Formation of 20-hydroxyeicosatetraenoic acid (20-HETE), the product of AA omega-hydroxylase was specifically localized in the entire proximal tubules (S1, S2, and S3 segments), whereas formation of 19-HETE, the product of omega-1-hydroxylase and epoxyeicosatrienoic acids (EETs), products of AA epoxygenase, was demonstrable throughout the tubule. Although distribution patterns were similar in SHR and WKY, formation of 19- and 20-HETE in the proximal tubules was higher in SHR, whereas the formation of EETs was not different between the two strains. In the proximal tubules, angiotensin II (ANG II) significantly stimulated epoxygenase activity (EETs formation), whereas parathyroid hormone (PTH) and epidermal growth factor (EGF) had no effect on epoxygenase but significantly stimulated omega-hydroxylase activity (20-HETE formation). Because P-450-AA metabolites have a wide and contrasting spectrum of biological and renal effects, from vasodilation to vasoconstriction and from inhibition to stimulation of Na(+)-K(+)-adenosinetriphosphatase, their localization to the specific nephron segments and differential stimulation of their formation by ANG II, PTH, and EGF may contribute not only to renal hemodynamics and blood pressure regulation but also to the regulation of renal sodium and water balance.

scholarly journals Stimulation by paraquat of microsomal and cytochrome P-450-dependent oxidation of glycerol to formaldehyde

1993 ◽  
Vol 295 (3) ◽  
pp. 781-786 ◽  
Author(s):  
L A Clejan ◽  
A I Cederbaum
Keyword(s):  
Superoxide Dismutase ◽  
Hydroxyl Radical ◽  
Glycerol Oxidation ◽  
Radical Scavengers ◽  
Microsomal Oxidation ◽  
Synergistic Interactions ◽  
Formaldehyde Production ◽  
Hydroxyl Radical Scavengers ◽  
Cytochrome P 450 ◽  
Haem Iron

Glycerol can be oxidized to formaldehyde by microsomes in a reaction that is dependent on cytochrome P-450. An oxidant derived from the interaction of H2O2 with iron was responsible for oxidizing the glycerol, with P-450 suggested to be necessary to produce H2O2 and reduce non-haem iron. The effect of paraquat on formaldehyde production from glycerol and whether paraquat could replace P-450 in supporting this reaction were studied. Paraquat increased NADPH-dependent microsomal oxidation of glycerol; the stimulation was inhibited by glutathione, catalase, EDTA and desferrioxamine, but not by superoxide dismutase or hydroxyl-radical scavengers. The paraquat stimulation was also inhibited by inhibitors, substrate and ligand for P-4502E1 (pyrazole-induced P-450 isozyme), as well as by anti-(P-4502E1) IgG. These results suggest that P-450 still played an important role in glycerol oxidation, even in the presence of paraquat. Purified NADPH-cytochrome P-450 reductase did not oxidize glycerol to formaldehyde; some oxidation, however, did occur in the presence of paraquat. Reductase plus P-4502E1 oxidized glycerol, and a large stimulation was observed in the presence of paraquat. Rates in the presence of P-450, reductase and paraquat were more than additive than the sums from the reductase plus P-450 and reductase plus paraquat rates, suggesting synergistic interactions between paraquat and P-450. These results indicate that paraquat increases oxidation of glycerol to formaldehyde by microsomes and reconstituted systems, that H2O2 and iron play a role in the overall reaction, and that paraquat can substitute, in part, for P-450 in supporting oxidation of glycerol. However, cytochrome P-450 is required for elevated rates of formaldehyde production even in the presence of paraquat.

A potassium-induced mitochondrial protein related to aldosterone biosynthesis

1983 ◽  
Vol 245 (5) ◽  
pp. E449-E456
Author(s):  
C. Meuli ◽  
J. Muller
Keyword(s):  
Molecular Weight ◽  
Adrenal Cortex ◽  
Time Course ◽  
Adrenal Glands ◽  
Mitochondrial Protein ◽  
Zona Glomerulosa ◽  
Mitochondrial Cytochrome ◽  
Potassium Intake ◽  
Cytochrome P 450 ◽  
Stimulation Of

Late steps of aldosterone biosynthesis, i.e., the conversions of corticosterone to 18-hydroxycorticosterone and aldosterone, are catalyzed by a mitochondrial cytochrome P-450. Resumption of potassium intake by potassium-depleted rats resulted within 2 days in a marked stimulation of these conversions, as reflected by increased production of aldosterone and 18-hydroxycorticosterone and decreased outputs of deoxycorticosterone, corticosterone, and 18-hydroxy-11-deoxycorticosterone by incubated capsular portions of the adrenal glands. The stimulation of aldosterone biosynthesis was accompanied by the appearance of a protein with a molecular weight of about 49,000 in the mitochondria of the zona glomerulosa but not of the inner zones of the adrenal cortex. Over 48 h of potassium repletion, the amount of this protein increased in parallel with the activity of the final steps of aldosterone biosynthesis. According to its molecular weight, its zone specificity, and the time course of its appearance, this protein might represent the steroid 18-methyl oxidase (cytochrome P-450CMO for corticosterone methyl oxidase) that catalyzes the conversion of corticosterone to 18-hydroxycorticosterone and aldosterone.

scholarly journals Uroporphyria produced in mice by 20-methylcholanthrene and 5-aminolaevulinic acid

1988 ◽  
Vol 253 (2) ◽  
pp. 357-362 ◽  
Author(s):  
A J Urquhart ◽  
G H Elder ◽  
A G Roberts ◽  
R W Lambrecht ◽  
P R Sinclair ◽  
...  
Keyword(s):  
Specific Form ◽  
Free Access ◽  
Uroporphyrinogen Decarboxylase ◽  
Continuous Administration ◽  
Aminolaevulinic Acid ◽  
Haem Biosynthesis ◽  
Intraperitoneal Dose ◽  
Polyhalogenated Aromatic Hydrocarbons ◽  
Cytochrome P 450 ◽  
Stimulation Of

Iron-loaded male C57BL/6 mice allowed free access to an aqueous solution of 5-aminolaevulinic acid (ALA) (2 mg/ml) as their only drink, develop severe uroporphyria within 9 days of a single intraperitoneal dose of 20-methylcholanthrene (MC) (125 mg/kg). At 21 days, uroporphyrinogen decarboxylase (EC 4.1.1.37) activities are less than 10% of control activities. The porphyria is not dependent on pretreatment with iron and persists for at least 21 days after withdrawal of ALA. The same intraperitoneal dose of MC does not produce porphyria within 21 days when given without ALA. Continuous administration of ALA markedly accelerates the onset of porphyria in iron-loaded male C57BL/6 mice after a single intraperitoneal dose of hexachlorobenzene (200 mg/kg); mice given phenobarbitone and ALA do not become porphyric. MC with ALA does not produce porphyria in iron-loaded male DBA/2 mice. At least two separate events are needed to produce uroporphyria in mammals: induction of a specific form of cytochrome P-450 and stimulation of the formation of intermediates of haem biosynthesis in the liver. These results show that severe, persistent porphyria can be produced in mammals by compounds other than polyhalogenated aromatic hydrocarbons and suggest that a similar mechanism underlies the porphyrogenic action of halogenated and non-halogenated compounds.

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