SPECIES DIFFERENCES IN THE ELIMINATION OF A PPAR AGONIST HIGHLIGHTED BY OXIDATIVE METABOLISM OF ITS ACYL GLUCURONIDE

2005 ◽  
Author(s):  
C. J. Kochansky
Keyword(s):  
Oxidative Metabolism ◽  
Species Differences ◽  
Ppar Agonist ◽  
Acyl Glucuronide

FORMATION AND PROTEIN BINDING OF THE ACYL GLUCURONIDE OF A LEUKOTRIENE B4 ANTAGONIST (SB-209247): RELATION TO SPECIES DIFFERENCES IN HEPATOTOXICITY

2004 ◽  
Vol 33 (2) ◽  
pp. 271-281 ◽  
Author(s):  
Jane R. Kenny ◽  
James L. Maggs ◽  
Justice N. A. Tettey ◽  
Andrew W. Harrell ◽  
Steven G. Parker ◽  
...  
Keyword(s):  
Protein Binding ◽  
Species Differences ◽  
Leukotriene B4 ◽  
Acyl Glucuronide

scholarly journals Cross-Species Differential Plasma Protein Binding of MBX-102/JNJ39659100: A Novel PPAR- Agonist

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-10 ◽  
Author(s):  
Holly J. Clarke ◽  
Francine Gregoire ◽  
Fang Ma ◽  
Robert Martin ◽  
Spring Zhao ◽  
...  
Keyword(s):  
Protein Binding ◽  
Plasma Protein Binding ◽  
Plasma Protein ◽  
Species Differences ◽  
Free Drug ◽  
Drug Binding ◽  
Mouse Serum ◽  
Drug Levels ◽  
Ppar Agonist ◽  
Interspecies Differences

Drug binding to plasma proteins restricts their free and active concentrations, thereby affecting their pharmacokinetic properties. Species differences in plasma protein levels complicate the understanding of interspecies pharmacodynamic and toxicological effects. MBX-102 acid/JNJ39659100 is a novel PPAR- agonist in development for the treatment of type 2 diabetes. Studies were performed to evaluate plasma protein binding to MBX-102 acid and evaluate species differences in free drug levels. Equilibrium dialysis studies demonstrated that MBX-102 acid is highly bound (>98%) to human, rat and mouse albumin and that free MBX-102 acid levels are higher in rodent than in human plasma. Interspecies differences in free drug levels were further studied using PPAR- transactivation assays and a newly developed PPAR- corepressor displacement (biochemical) assay. PPAR- transactivation and corepressor displacement by MBX-102 acid was higher in rat and mouse serum than human serum. These results confirm the relevance of interspecies differences in free MBX-102 acid levels.

Extrapolation of Diclofenac Clearance from in Vitro Microsomal Metabolism Data: Role of Acyl Glucuronidation and Sequential Oxidative Metabolism of the Acyl Glucuronide

2002 ◽  
Vol 303 (3) ◽  
pp. 969-978 ◽  
Author(s):  
Sanjeev Kumar ◽  
Koppara Samuel ◽  
Ramaswamy Subramanian ◽  
Matthew P. Braun ◽  
Ralph A. Stearns ◽  
...  
Keyword(s):  
Oxidative Metabolism ◽  
Microsomal Metabolism ◽  
Acyl Glucuronide

Species Differences in Oxidative Metabolism of Regorafenib

Xenobiotica ◽  
2022 ◽  
pp. 1-13
Author(s):  
Ayaka Kojima ◽  
Ayuka Sogabe ◽  
Masayuki Nadai ◽  
Miki Katoh
Keyword(s):  
Oxidative Metabolism ◽  
Species Differences

Scanning Electron Microscopy of Fish Scales as an Adjunctive Aid in Speciation

1972 ◽  
Vol 30 ◽  
pp. 394-395
Author(s):  
Edward D. DeLamater ◽  
Walter R. Courtenay ◽  
Cecil Whitaker
Keyword(s):  
Electron Microscopy ◽  
Scanning Electron Microscopy ◽  
Lateral Line ◽  
Species Differences ◽  
Fish Scale ◽  
Fish Scales ◽  
Anterior Border ◽  
The University ◽  
Multiple Holes ◽  
Scanning Electron

Comparative scanning electron microscopy studies of fish scales of different orders, families, genera and species within genera have demonstrated differences which warrant elaboration. These differences in detail appear to be sufficient to act as “fingerprints”, at least, for family differences. To date, the lateral line scales have been primarily studied. These demonstrate differences in the lateral line canals; the pattern of ridging with or without secondary protuberances along the edges; the pattern of spines or their absence on the anterior border of the scales; the presence or absence of single or multiple holes on the ventral and dorsal sides of the lateral line canal covers. The distances between the ridges in the pattern appear likewise to be important.A statement of fish scale structure and a comparison of family and species differences will be presented.The authors wish to thank Dr. Donald Marzalek and Mr. Wallace Charm of the Marine and Atmospheric Laboratory of the University of Miami and Dr. Sheldon Moll and Dr. Richard Turnage of AMR for their exhaustive help in these preliminary studies.

Tobacco Mosaic Virus-Infected Tissue

1985 ◽  
Vol 43 ◽  
pp. 510-511
Author(s):  
Egbert W. Henry
Keyword(s):  
Nicotiana Tabacum ◽  
Tobacco Mosaic Virus ◽  
Chlorogenic Acid ◽  
Mosaic Virus ◽  
Host Resistance ◽  
Oxidative Metabolism ◽  
Leaf Tissue ◽  
Vein Clearing ◽  
Basal Septum ◽  
Concentration Levels

Tobacco mosaic virus (TMV) infection has been studied in several investigations of Nicotiana tabacum leaf tissue. Earlier studies have suggested that TMV infection does not have precise infective selectivity vs. specific types of tissues. Also, such tissue conditions as vein banding, vein clearing, liquification and suberization may result from causes other than direct TMV infection. At the present time, it is thought that the plasmodesmata, ectodesmata and perhaps the plasmodesmata of the basal septum may represent the actual or more precise sites of TMV infection.TMV infection has been implicated in elevated levels of oxidative metabolism; also, TMV infection may have a major role in host resistance vs. concentration levels of phenolic-type enzymes. Therefore, enzymes such as polyphenol oxidase, peroxidase and phenylalamine ammonia-lyase may show an increase in activity in response to TMV infection. It has been reported that TMV infection may cause a decrease in o-dihydric phenols (chlorogenic acid) in some tissues.

Arabidopsis 4-COUMAROYL-COA LIGASE 8 contributes to the biosynthesis of the benzenoid ring of coenzyme Q in peroxisomes

2019 ◽  
Vol 476 (22) ◽  
pp. 3521-3532
Author(s):  
Eric Soubeyrand ◽  
Megan Kelly ◽  
Shea A. Keene ◽  
Ann C. Bernert ◽  
Scott Latimer ◽  
...  
Keyword(s):  
Oxidative Metabolism ◽  
Time Course ◽  
Reverse Genetics ◽  
De Novo ◽  
Coenzyme Q ◽  
Control Level ◽  
Wild Type ◽  
Fluorescent Reporters ◽  
Coa Ligase ◽  
Peroxisomal Targeting

Plants have evolved the ability to derive the benzenoid moiety of the respiratory cofactor and antioxidant, ubiquinone (coenzyme Q), either from the β-oxidative metabolism of p-coumarate or from the peroxidative cleavage of kaempferol. Here, isotopic feeding assays, gene co-expression analysis and reverse genetics identified Arabidopsis 4-COUMARATE-COA LIGASE 8 (4-CL8; At5g38120) as a contributor to the β-oxidation of p-coumarate for ubiquinone biosynthesis. The enzyme is part of the same clade (V) of acyl-activating enzymes than At4g19010, a p-coumarate CoA ligase known to play a central role in the conversion of p-coumarate into 4-hydroxybenzoate. A 4-cl8 T-DNA knockout displayed a 20% decrease in ubiquinone content compared with wild-type plants, while 4-CL8 overexpression boosted ubiquinone content up to 150% of the control level. Similarly, the isotopic enrichment of ubiquinone's ring was decreased by 28% in the 4-cl8 knockout as compared with wild-type controls when Phe-[Ring-13C6] was fed to the plants. This metabolic blockage could be bypassed via the exogenous supply of 4-hydroxybenzoate, the product of p-coumarate β-oxidation. Arabidopsis 4-CL8 displays a canonical peroxisomal targeting sequence type 1, and confocal microscopy experiments using fused fluorescent reporters demonstrated that this enzyme is imported into peroxisomes. Time course feeding assays using Phe-[Ring-13C6] in a series of Arabidopsis single and double knockouts blocked in the β-oxidative metabolism of p-coumarate (4-cl8; at4g19010; at4g19010 × 4-cl8), flavonol biosynthesis (flavanone-3-hydroxylase), or both (at4g19010 × flavanone-3-hydroxylase) indicated that continuous high light treatments (500 µE m−2 s−1; 24 h) markedly stimulated the de novo biosynthesis of ubiquinone independently of kaempferol catabolism.

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