Action of Ebselen on rat hepatic microsomal enzyme-catalyzed fatty acid chain elongation, desaturation, and drug biotransformation.

@article{Laguna1989ActionOE,
  title={Action of Ebselen on rat hepatic microsomal enzyme-catalyzed fatty acid chain elongation, desaturation, and drug biotransformation.},
  author={Juan Carlos Laguna and Mahmoud N Nagi and Lynda Cook and Dominick L. Cinti},
  journal={Archives of biochemistry and biophysics},
  year={1989},
  volume={269 1},
  pages={
          272-83
        }
}
In the previous study, the organoselenium-containing anti-inflammatory agent, Ebselen, was found to disrupt both hepatic microsomal NADH- and NADPH-dependent electron transport chains. In the current investigation, we focus on the action of Ebselen on three separate metabolic reactions, namely, fatty acid chain elongation, desaturation, and drug biotransformation, which utilize reducing equivalents via these microsomal electron transport pathways. Both NADH-dependent and NADPH-dependent chain… Expand
19 Citations
Enzyme site-specific changes in hepatic microsomal fatty acid chain elongation in streptozotocin-induced diabetic rats.
TLDR
Analysis of the activities of the four enzymatic components showed that only one enzyme, the condensing enzyme, was altered by the diabetic state, which supports the notion of multiple condensing enzymes or chain elongation systems. Expand
Fibrates modify rat hepatic fatty acid chain elongation and desaturation in vitro.
TLDR
Fibrates (GFB) appeared to behave as mixed non-competitive inhibitors with respect to malonyl-CoA when the rate limiting step of elongation, the condensing enzyme, is assayed. Expand
Spectrophotometric assay for the condensing enzyme activity of the microsomal fatty acid chain elongation system.
TLDR
A rapid and simple spectrophotometric method was developed to measure the activity of the condensing enzyme component of the microsomal fatty acid chain elongation system and compares favorably with the activity obtained by the radioactive method. Expand
Regulation by carbohydrate and clofibric acid of palmitoyl-CoA chain elongation in the liver of rats
TLDR
It is suggested that carbohydrate induces PCE as well as SCD activity to increase the hepatic 18∶1 content in rat liver, and the increased PCE activity seems to be responsible for the further increase in 18∵1n−9 when carbohydrate is administered in combination with clofibric acid. Expand
Inhibition of rat liver microsomal fatty acid chain elongation by gemfibrozil in vitro
TLDR
Gemfibrozil seems to act by inhibiting the rate‐limiting step of the elongation process, the condensing reaction, without discriminating among the proposed three different condensing enzymes, devoted to condensation of saturated, mono‐unsaturated and polyunsaturated acyl‐CoA substrates. Expand
Effects of perfluorocarboxylic acids on the activities of acyl-CoA elongations in vivo and in vitro.
Effects of perfluorocarboxylic acids (PFCAs) on proportions of oleic acid and cis-vaccenic acid through acyl-CoA chain elongation systems have been studied in the liver of rats. Administration ofExpand
Selective modification of rat hepatic microsomal fatty acid chain elongation and desaturation by fibrates: relationship with peroxisome proliferation
TLDR
The time‐course of the effect of clofibrate, bezafibrate and gemfibrozil on lipid plasma levels and palmitoyl, palmitoleoyl‐ and γ‐linolenoyl-CoA elongase activities, and microsomal electron transport chains, as well as the correlation with the peroxisomal proliferation phenomenon have been studied in male Sprague‐Dawley rats. Expand
The fatty acid chain elongation system of mammalian endoplasmic reticulum.
TLDR
The critical, inducible and rate-limiting condensing enzyme has resisted solubilization and purification; the purification of the other components has met with limited success. Expand
Evidence for insulin dependent hepatic microsomal gamma-linolenic acid chain elongation in spontaneously diabetic Wistar BB rats.
TLDR
The liver microsomal gamma-linolenoyl-CoA elongation was decreased in diabetic Wistar BB rats during both normo- and hyperglycemic periods and restored during the hypoglycemic period following insulin treatment, which support the non-parallel relationship between the chain elongation system and the glycemia. Expand
Ebselen, a selenoorganic compound as glutathione peroxidase mimic.
  • H. Sies
  • Chemistry, Medicine
  • Free radical biology & medicine
  • 1993
TLDR
Model experiments in vitro with liposomes, microsomes, isolated cells, and organs show that the protection against oxidative challenge afforded by ebselen can be explained largely by the activity as GSH peroxidase mimic. Expand
...
1
2
...

References

SHOWING 1-10 OF 30 REFERENCES
Disruption of rat hepatic microsomal electron transport chains by the selenium-containing anti-inflammatory agent Ebselen.
TLDR
The addition of Ebselen to a suspension of hepatic microsomes from either untreated or phenobarbital-treated rats did not result in any spectral change characteristic of type I, type II, or reverse type I. Expand
Effect of the peroxisomal proliferator di(2-ethylhexyl)phthalate on component reactions of the rat hepatic microsomal fatty acid chain elongation system and on other hepatic lipogenic enzymes.
TLDR
The feeding of 2% di(2-ethylhexyl)phthalate to rats and in vitro addition of DEHP indicate that the peroxisomal proliferator induces only the condensing enzyme which is the regulatory and rate-limiting step of elongation sequence. Expand
Site of inhibition of rat liver microsomal fatty acid chain elongation system by dec-2-ynoyl coenzyme A. Possible mechanism of inhibition.
TLDR
It is proposed that delta 2 10 identical to 1-CoA inactivates trans-2-enoyl- CoA reductase by covalently binding to a critical sulfhydryl group at or in close proximity to the active site of the enzyme. Expand
An analysis of partial reactions in the overall chain elongation of saturated and unsaturated fatty acids by rat liver microsomes.
TLDR
Findings show that condensation is rate-limiting and implicate it in overall control of chain elongation, and a difference in the rate of Nethylmaleimide inhibition for condensation activity with palmitoyl-CoA versus unsaturated substrates provides direct evidence for the involvement of at least one different enzyme in the condensation systems using saturated versus polyunsaturated primers. Expand
Evidence for multiple condensing enzymes in rat hepatic microsomes catalyzing the condensation of saturated, monounsaturated, and polyunsaturated acyl coenzyme A.
TLDR
The competitive substrate studies, those of dietary and DEHP administration, and the differential action of chymotrypsin strongly suggest the existence of at least three discrete condensing enzymes catalyzing the condensation of saturated, monounsaturated, and polyunsaturated acyl-CoAs. Expand
The effect of bovine serum albumin on partial reactions of palmitoyl-CoA chain elongation by rat liver microsomes.
TLDR
The results demonstrate that albumin not only alleviates a substrate induced inhibition but also regulates the metabolic fate of 2-trans-octadecenoyl-coA and in this regard may possibly substitute for acyl-CoA binding proteins. Expand
The enzymic chain elongation of fatty acids by rat-liver microsomes.
  • D. Nugteren
  • Chemistry, Medicine
  • Biochimica et biophysica acta
  • 1965
TLDR
The chain elongation described here can clearly be distinguished from synthesis de novo in the supernatant and from a proposed reversal of the mitochondrial β-oxidation. Expand
The preferred metabolic pathway from linoleic acid to arachidonic acid in vitro.
TLDR
The desaturation of eicosa-8,11,14-trienoic acid is strongly enhanced by linoleic and γ-linolenic acids which may account for its non-accumulation in tissue lipids. Expand
Biochemical properties of short- and long-chain rat liver microsomal trans-2-enoyl coenzyme A reductase.
TLDR
The role of NADPH-cytochrome P-450 reductase in the microsomal elongation of fatty acids appears to be at the level of the first reduction step. Expand
Pyridine Nucleotide-Dependent Electron Transport in Kidney Cortex Microsomes: Interaction with Desaturase and Other Microsomal Mixed-Function Oxidases
Rat kidney cortex microsomes contain both cytochrome b 5 and its flavoprotein reductase, yet do not catalyze fatty acyl-CoA desaturation. This inactivity was unaltered by feeding a high-carbohydrateExpand
...
1
2
3
...