2002
DOI: 10.1124/dmd.30.4.355
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Abstract: This article is available online at http://dmd.aspetjournals.orgThe cytochrome P450 enzymes are involved in the biotransformation of both xenobiotic and endobiotic hydrophobic compounds, implicated in the bioactivation of certain procarcinogens (e.g., benzo-[a]pyrene), and responsible for many metabolism-based drug-drug interactions (Wrighton and Stevens, 1992). Consequently, the goal of drug metabolism and toxicology labs is to not only to determine the P450 isoform contribution to the metabolism of a given c… Show more

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Cited by 255 publications
(226 citation statements)
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“…Substrate concentration response experiments resulted in a sigmoidal curve with a Hill coefficient of 2.92, indicating that PBP1b-catalyzed glycosyltransfer may display positive cooperativity (Fig. 2B) (20,21). This observation is in line with a recent surface plasmon resonance study whereby low concentrations of GTase acceptor substrate analogs were found to increase moenomycin donor site affinity in the for the dansyl-lipid II coupled assay (18).…”
Section: Resultssupporting
confidence: 76%
“…Substrate concentration response experiments resulted in a sigmoidal curve with a Hill coefficient of 2.92, indicating that PBP1b-catalyzed glycosyltransfer may display positive cooperativity (Fig. 2B) (20,21). This observation is in line with a recent surface plasmon resonance study whereby low concentrations of GTase acceptor substrate analogs were found to increase moenomycin donor site affinity in the for the dansyl-lipid II coupled assay (18).…”
Section: Resultssupporting
confidence: 76%
“…As shown in Fig. 4C, the sulfation of ractopamine was fitted to substrate inhibition kinetics, which was further confirmed by an Eadie Hofstee plot, based on v versus v/[S], with a hook in the upper quadrant (37). Conversely, the sulfation of salbutamol was fitted to Michaelis Menten kinetics, which was further confirmed by a linear Eadie Hofstee plot (37) (Fig.…”
Section: Miscellaneous Methodsmentioning
confidence: 66%
“…With the linear increase of the turnover rates at higher substrate concentrations, apparent K m,2 and V max,2 are difficult to estimate. Such profiles, despite using single enzyme sources, have already been observed for CYP1A1 with aminopyrine (Inouye et al, 2000), CYP1A2 with 1-methoxy-4-nitrobenzene (Miller and Guengerich, 2001), CYP2C9 with naproxene (Korzekwa et al, 1998;Hutzler and Tracy, 2002), and CYP3A4 with levo-␣-acetylmethadol or naphthalene (Korzekwa et al, 1998;Oda and Kharasch, 2001), but not for CYP2C19. If these kinds of biphasic plots are obtained, Korzekwa et al (1998) proposed that two substrate molecules at one time have access to the reactive oxygen.…”
Section: Resultsmentioning
confidence: 83%