The “Albumin Effect” and in Vitro-in Vivo Extrapolation: Sequestration of Long-Chain Unsaturated Fatty Acids Enhances Phenytoin Hydroxylation by Human Liver Microsomal and Recombinant Cytochrome P450 2C9

2008 ◽  
Vol 36 (5) ◽  
pp. 870-877 ◽  
Author(s):  
Andrew Rowland ◽  
David J. Elliot ◽  
Kathleen M. Knights ◽  
Peter I. Mackenzie ◽  
John O. Miners
Keyword(s):  
Fatty Acids ◽  
Cytochrome P450 ◽  
Human Liver ◽  
Unsaturated Fatty Acids ◽  
Cytochrome P450 2C9 ◽  
In Vivo Extrapolation ◽  
Long Chain

scholarly journals Effect of a New Prokinetic Agent DA-9701 Formulated with Corydalis Tuber and Pharbitidis Semen on Cytochrome P450 and UDP-Glucuronosyltransferase Enzyme Activities in Human Liver Microsomes

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Hye Young Ji ◽  
Kwang Hyeon Liu ◽  
Ji Hyeon Jeong ◽  
Dae-Young Lee ◽  
Hyun Joo Shim ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Human Liver ◽  
Liver Microsomes ◽  
Human Liver Microsomes ◽  
Udp Glucuronosyltransferase ◽  
Index Value ◽  
Tuber Extract ◽  
Corydalis Tuber

DA-9701 is a new botanical drug composed of the extracts of Corydalis tuber and Pharbitidis semen, and it is used as an oral therapy for the treatment of functional dyspepsia in Korea. The inhibitory potentials of DA-9701 and its component herbs, Corydalis tuber and Pharbitidis semen, on the activities of seven major human cytochrome P450 (CYP) enzymes and four UDP-glucuronosyltransferase (UGT) enzymes in human liver microsomes were investigated using liquid chromatography-tandem mass spectrometry. DA-9701 and Corydalis tuber extract slightly inhibited UGT1A1-mediated etoposide glucuronidation, with 50% inhibitory concentration (IC50) values of 188 and 290 μg/mL, respectively. DA-9701 inhibited CYP2D6-catalyzed bufuralol1′-hydroxylation with an inhibition constant (Ki) value of 6.3 μg/mL in a noncompetitive manner. Corydalis tuber extract competitively inhibited CYP2D6-mediated bufuralol1′-hydroxylation, with aKivalue of 3.7 μg/mL, whereas Pharbitidis semen extract showed no inhibition. The volume in which the dose could be diluted to generate an IC50equivalent concentration (volume per dose index) value of DA-9701 for inhibition of CYP2D6 activity was 1.16 L/dose, indicating that DA-9701 may not be a potent CYP2D6 inhibitor. Further clinical studies are warranted to evaluate thein vivoextent of the observedin vitrointeractions.

scholarly journals Overlapping Repressor Binding Sites Result in Additive Regulation of Escherichia coli FadH by FadR and ArcA

2010 ◽  
Vol 192 (17) ◽  
pp. 4289-4299 ◽  
Author(s):  
Youjun Feng ◽  
John E. Cronan
Keyword(s):  
Escherichia Coli ◽  
Fatty Acids ◽  
Cyclic Amp ◽  
Unsaturated Fatty Acids ◽  
Genetic Regulation ◽  
Receptor Protein ◽  
Anaerobic Conditions ◽  
Mobility Shift ◽  
Long Chain

ABSTRACT Escherichia coli fadH encodes a 2,4-dienoyl reductase that plays an auxiliary role in β-oxidation of certain unsaturated fatty acids. In the 2 decades since its discovery, FadH biochemistry has been studied extensively. However, the genetic regulation of FadH has been explored only partially. Here we report mapping of the fadH promoter and document its complex regulation by three independent regulators, the fatty acid degradation FadR repressor, the oxygen-responsive ArcA-ArcB two-component system, and the cyclic AMP receptor protein-cyclic AMP (CRP-cAMP) complex. Electrophoretic mobility shift assays demonstrated that FadR binds to the fadH promoter region and that this binding can be specifically reversed by long-chain acyl-coenzyme A (CoA) thioesters. In vivo data combining transcriptional lacZ fusion and real-time quantitative PCR (qPCR) analyses indicated that fadH is strongly repressed by FadR, in agreement with induction of fadH by long-chain fatty acids. Inactivation of arcA increased fadH transcription by >3-fold under anaerobic conditions. Moreover, fadH expression was increased 8- to 10-fold under anaerobic conditions upon deletion of both the fadR and the arcA gene, indicating that anaerobic expression is additively repressed by FadR and ArcA-ArcB. Unlike fadM, a newly reported member of the E. coli fad regulon that encodes another auxiliary β-oxidation enzyme, fadH was activated by the CRP-cAMP complex in a manner similar to those of the prototypical fad genes. In the absence of the CRP-cAMP complex, repression of fadH expression by both FadR and ArcA-ArcB was very weak, suggesting a possible interplay with other DNA binding proteins.

In vitro and in vivo fate of saturated and unsaturated fatty acids during development of insects

1974 ◽  
Vol 360 (3) ◽  
pp. 289-297 ◽  
Author(s):  
A.M. Municio ◽  
J.M. Odriozola ◽  
M.A. Pérez-Albarsanz ◽  
J.A. Ramos
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids

Effect of Albumin on Human Liver Microsomal and Recombinant CYP1A2 Activities: Impact on In Vitro-In Vivo Extrapolation of Drug Clearance

2012 ◽  
Vol 40 (5) ◽  
pp. 982-989 ◽  
Author(s):  
Nitsupa Wattanachai ◽  
Wichittra Tassaneeyakul ◽  
Andrew Rowland ◽  
David J. Elliot ◽  
Kushari Bowalgaha ◽  
...  
Keyword(s):  
Human Liver ◽  
Drug Clearance ◽  
In Vivo Extrapolation

Binding of Inhibitory Fatty Acids Is Responsible for the Enhancement of UDP-Glucuronosyltransferase 2B7 Activity by Albumin: Implications for in Vitro-in Vivo Extrapolation

2007 ◽  
Vol 321 (1) ◽  
pp. 137-147 ◽  
Author(s):  
Andrew Rowland ◽  
Paraskevi Gaganis ◽  
David J. Elliot ◽  
Peter I. Mackenzie ◽  
Kathleen M. Knights ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Udp Glucuronosyltransferase ◽  
In Vivo Extrapolation

Absorption of medium chain fatty acids and medium chain triglycerides, in vitro and in vivo, in comparison with long chain triglycerides

1970 ◽  
Vol 5 (2) ◽  
pp. 143-144
Author(s):  
Masasuke Masuda ◽  
S. Hosoda ◽  
Y. Tokura ◽  
Y. Yoshida ◽  
K. Kashima ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Medium Chain Triglycerides ◽  
Medium Chain ◽  
Medium Chain Fatty Acids ◽  
Long Chain Triglycerides ◽  
Long Chain ◽  
Chain Fatty Acids
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