[3] Analysis of enzyme progress curves by nonlinear regression

Duggleby, Ronald G.

doi:10.1016/0076-6879(95)49031-0

Cited by 212 publications

(135 citation statements)

References 25 publications

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“…Curve C in Fig. 1 was first fitted to an integrated rate equation derived from a "ping-pong" reaction mechanism (17). This model assumes that LBP first receives an LPS in a bimolecular reaction with an LPS aggregate, then transfers LPS in a second bimolecular reaction with R-HDL.…”

Section: Progress Curves For Transfer Of Lps To R-hdl Fit a Model Formentioning

confidence: 99%

Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids.

Yu¹,

Hailman²,

Wright³

1997

J. Clin. Invest.

217

155

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Lipopolysaccharide binding protein (LBP) is a plasma protein known to facilitate the diffusion of bacterial LPS (endotoxin). LBP catalyzes movement of LPS monomers from LPS aggregates to HDL particles, to phospholipid bilayers, and to a binding site on a second plasma protein, soluble CD14 (sCD14). sCD14 can hasten transfer by receiving an LPS monomer from an LPS aggregate, and then surrendering it to an HDL particle, thus acting as a soluble "shuttle" for an insoluble lipid. Here we show that LBP and sCD14 shuttle not only LPS, but also phospholipids. Phosphatidylinositol (PI), phosphatidylcholine, and a fluorescently labeled derivative of phosphatidylethanolamine (R-PE) are each transferred by LBP from membranes to HDL particles. The transfer could be observed using recombinant LBP and sCD14 or whole human plasma, and the plasma-mediated transfer of PI could be blocked by anti-LBP and partially inhibited by anti-CD14. sCD14 appears to act as a soluble shuttle for phospholipids since direct binding of PI and R-PE to sCD14 was observed and because addition of sCD14 accelerated transfer of these lipids. These studies define a new function for LBP and sCD14 and describe a novel mechanism for the transfer of phospholipids in blood. In further studies, we show evidence suggesting that LBP transfers LPS and phospholipids by reciprocal exchange: LBP-catalyzed binding of R-PE to LPS • sCD14 complexes was accompanied by the exit of LPS from sCD14, and LBP-catalyzed binding of R-PE to sCD14 was accelerated by prior binding of LPS to sCD14. Binding of one lipid is thus functionally coupled with the release of a second.

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Section: Progress Curves For Transfer Of Lps To R-hdl Fit a Model Formentioning

confidence: 99%

Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids.

Yu¹,

Hailman²,

Wright³

1997

J. Clin. Invest.

217

155

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“…The most important problem in progress curve analysis is the numerical complexity of the fitting procedure (Duggleby and Daniel, 1995). While the kinetic laws are formulated as rates the experimental data are collected in terms of concentrations.…”

Section: Introductionmentioning

confidence: 99%

Model-based experimental analysis of enzyme kinetics in aqueous–organic biphasic systems

Zavrel

Schmidt

Michalik

et al. 2007

Journal of Biotechnology

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“…The kinetic constants (K m and V max ) for the elimination of telithromycin from the hepatic and intestinal microsomes were calculated using a nonlinear regression method (7). The CL int for the elimination of telithromycin from the hepatic or intestinal microsomes was calculated by dividing the respective V max by the respective K m .…”

Section: Treatment With Eclpsmentioning

confidence: 99%

Effects of Escherichia coli Lipopolysaccharide on Telithromycin Pharmacokinetics in Rats: Inhibition of Metabolism via CYP3A

Lee

Cho

Jung

et al. 2008

Antimicrob Agents Chemother

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It has been reported that telithromycin is metabolized primarily via hepatic microsomal cytochrome P450 (CYP) 3A1/2 in rats and that the expression of hepatic and intestinal CYP3A decreases in rats pretreated with Escherichia coli lipopolysaccharide (ECLPS rats; an animal model of inflammation). Thus, it is possible that the area under the plasma concentration-time curve from 0 h to infinity (AUC 0-ؕ ) of intravenous and oral telithromycin is greater for ECLPS rats than for the controls. To assess this, the pharmacokinetic parameters of telithromycin were compared after intravenous and oral administration (50 mg/kg). After intravenous administration of telithromycin, the AUC 0-ؕ was significantly greater (by 83.4%) in ECLPS rats due to a significantly lower nonrenal clearance (by 44.5%) than in the controls. This may have been due to a significantly decreased hepatic metabolism of telithromycin in ECLPS rats. After oral administration of telithromycin, the AUC 0-ؕ in ECLPS rats was also significantly greater (by 140%) than in the controls and the increase was considerably greater than the 83.4% increase after intravenous administration. This could have been due to a decrease in intestinal metabolism in addition to a decreased hepatic metabolism of telithromycin in ECLPS rats.Telithromycin, a ketolide antibiotic, is the first of a new class of semisynthetic agents derived from erythromycin by the replacement of the sugar cladinose at position C-3 with a keto group. This alteration resulted in both improved pharmacokinetic properties and an improved spectrum of activity against community-acquired upper and lower respiratory tract pathogens compared to those of erythromycin (4). Telithromycin inhibits bacterial protein synthesis via two mechanisms, first by directly blocking the translation of mRNA and second by interfering with the assembly of new ribosomal units (5). Telithromycin has potent activities both in vitro and in vivo against common respiratory tract pathogens, including Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and group A beta-hemolytic streptococci, irrespective of their ␤-lactam or macrolide susceptibility (1). Its spectrum of activity also extends to atypical and intracellular pathogens (23). Lotter et al. (17) reported that telithromycin has antiinflammatory properties like those of conventional macrolides due to the inhibition of production of proinflammatory cytokines, which leads to a decreased formation of nitric oxide in Escherichia coli lipopolysaccharide (ECLPS)-treated mice.LPS is an active component in the outer membrane of gramnegative bacteria. ECLPS has been used as a classical inflammatory model for rats (9,27). Changes in the expression and mRNA levels of hepatic microsomal cytochrome P450 (CYP) isozymes have been reported for rats pretreated with ECLPS (ECLPS rats). For example, the expression and mRNA levels of hepatic CYP2C11, -2E1, and -3A2 decreased in male rats of the Fisher 344 or Sprague-Dawley strain 24 h after intraperitoneal injection of ECLP...

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[3] Analysis of enzyme progress curves by nonlinear regression

Cited by 212 publications

References 25 publications

Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids.

Lipopolysaccharide binding protein and soluble CD14 catalyze exchange of phospholipids.

Model-based experimental analysis of enzyme kinetics in aqueous–organic biphasic systems

Effects of Escherichia coli Lipopolysaccharide on Telithromycin Pharmacokinetics in Rats: Inhibition of Metabolism via CYP3A

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