Recombinant Cell Culture Research Articles

Analyzing mixtures of amino acids and carbohydrates using bi-modal integrated amperometric detection

Described in this work is a new detection methodology – bi-modal integrated amperometric detection – for identifying peaks and as a tool for solving difficult separation problems. Bi-modal integrated amperometry makes it possible to selectively detect amino acids, amino sugars, and carbohydrates following their separation by anion-exchange. Selectivity is gained by two different methods of integrating anodic current on an otherwise identical waveform. As with the single-mode integrated amperometry reported previously, the limits of detection are in the femtomole range and linear calibration plots are possible over three orders of magnitude. This new detection method does not require analyte derivatization. The practical utility of this new technique is demonstrated in the analysis of amino acids and sugars in a recombinant mammalian cell culture medium.

Development of a serum-free medium for the production of erythropoietin by suspension culture of recombinant Chinese hamster ovary cells using a statistical design

In order to develop a serum-free (SF) medium for the production of erythropoietin (EPO) by suspension culture of recombinant Chinese hamster ovary (rCHO) cells, a statistical optimization approach based on a Plackett–Burman design was adopted. A basal medium was prepared by supplementing Iscove’s modified Dulbecco’s medium (IMDM) with Fe(NO 3) 3 9H 2O, CuCl 2 and ZnSO 4 7H 2O which are generally contained in SF medium formulations. Insulin, transferrin and ethanolamine were also supplemented to the basal medium to determine their optimal concentrations. From this statistical analysis, glutamate, serine, methionine, phosphatidylcholine, hydrocortisone and pluronic F68 were identified as positive determinants for cell growth. The SF medium was formulated by supplementing the basal medium with components showing positive effects on cell growth in suspension culture. An EPO titer in this optimized SF medium was 79% of that in IMDM supplemented with 5% dialyzed fetal bovine serum (dFBS). Furthermore, the in vitro and in vivo biological activities of EPO produced in the SF medium were comparable to those produced in the serum-supplemented medium. Taken together, the results obtained here show that a Plackett–Burman design facilitates the development of SF media for the production of EPO by suspension culture of rCHO cells.

Recombinant domain IV of perlecan binds to nidogens, laminin-nidogen complex, fibronectin, fibulin-2 and heparin.

Domain IV of mouse perlecan, which consists of 14 immunoglobulin superfamily (IG) modules, was prepared from recombinant human cell culture medium in the form of two fragments, IV-1 (IG2-9, 100 kDa) and IV-2 (IG10-15, 66 kDa). Both fragments bound to a heparin column, being eluted at ionic strengths either below (IV-2) or above (IV-1) physiological level, and could thus be readily purified. Electron microscopy demonstrated an elongated shape (20-25 nm), and folding into a native structure was indicated by immunological assay and CD spectroscopy. Solid-phase and surface plasmon resonance assays demonstrated strong binding of fragment IV-1 to fibronectin, nidogen-1, nidogen-2 and the laminin-1-nidogen-1 complex, with Kd values in the range 4-17 nM. The latter binding apparently occurs through nidogen-1, as shown by the formation of ternary complexes. Only moderate binding was observed for fibulin-2 and collagen IV and none for fibulin-1 and BM-40. Fragment IV-2 showed a more restricted pattern of binding, with only weaker binding to fibronectin and fibulin-2. None of these activities could be demonstrated for recombinant fragments corresponding to the N-terminal perlecan domains I to III. This indicates a special role for domain IV in the integration of perlecan into basement membranes and other extracellular structures via protein-protein interactions.

On the development of an intelligent control system for recombinant cell culture

To produce a recombinant protein, it is critically important to optimize and control bioprocesses based on knowledge of a cell's genetic, metabolic, and kinetic behavior. It is, however, not straightforward due to the fact that the biosystem is highly nonlinear, time variant, and complex. In this paper, we discuss three kinds of intelligent control systems for control of fed-batch cultivation of recombinant E. coli and yeast, namely, fuzzy pH-stat, fuzzy neural network, and fuzzy control coupled with a neural network estimator. In a fuzzy pH-stat control system, the relationship between pH change in the medium and glucose consumption rate is modeled by a fuzzy set and thereafter used to control the feed rate of glucose to obtain cell density as high as 72 g/L. In a fuzzy neural network (FNN) control system, a FNN was constructed to learn fuzzy control inference and then was applied to fed-batch cultivation of recombinant E. coli to attain a high expression of recombinant protein. In addition, we developed a fuzzy control system coupled with neural network estimators that can on-line estimate residual glucose and galactose concentrations, which were utilized to control the feed rate of glucose (during the cell growth phase) and the feed rate of galactose (during the expression phase). Results of these control strategies are presented and their usefulness in the fed-batch cultivation of recombinant strains is demonstrated. The idea behind these studies is to utilize predetermined experimental data to develop repetitive learning control using intelligent techniques.

Multivalent vaccine to treat B-cell lymphoma or leukemia antitumor recombinant vaccine production, chimeric antibody engineering and dihydrofolate-reductase-mediated gene amplification in recombinant T-lymphocyte cell culture : Genitope World 9741 244; 6 November 1997

Multivalent vaccine to treat B-cell lymphoma or leukemia antitumor recombinant vaccine production, chimeric antibody engineering and dihydrofolate-reductase-mediated gene amplification in recombinant T-lymphocyte cell culture : Genitope World 9741 244; 6 November 1997

Changing Residue 338 in Human Factor IX from Arginine to Alanine Causes an Increase in Catalytic Activity

This study was designed to identify functionally important factor IX (FIX) residues. Using recombinant techniques and cell culture, we produced a mutant FIX with arginine at 338 changed to alanine (R338A-FIX). This molecule had approximately 3 times greater clotting activity than that of wild type FIX (wt-FIX) in the activated partial thromboplastin assay. R338A-FIX reacted normally with a panel of three FIX specific monoclonal antibodies and migrated on sodium dodecyl sulfate-polyacrylamide gels indistinguishably from wt-FIX. Using functional assays, we determined that R338A-FIXa's Kd for factor VIIIa (FVIIIa) was similar to that of wt-FIXa. Our kinetic analysis, using factor X as substrate, indicated that the mutation's major effects were a 3-fold increase in kcat and a 2-fold decrease in Km both manifested only in the presence of FVIIIa. R338A-FIXa's increased catalytic efficiency did not result from ablation of a thrombin sensitive site, reported to occur at arginine 338, since in our assays the thrombin inhibitor, hirudin, had no effect on activity of either wt-FIXa or R338A-FIXa. R338A-FIXa and wt-FIXa had equal activity, with or without FVIIIa, toward the synthetic substrate, methylsulfonyl-D-cyclohexylglycyl-arginine-p-nitroanilide. Interestingly, R338A-FIXa had reduced affinity for heparin. Therefore, we propose that R338A-FIXa's increased activity is not due to an allosteric effect on the active site, but that the Arg-338 residue is part of an exosite that binds both factor X and the mucopolysaccharide, heparin.

Engineering Chinese hamster ovary (CHO) cells to achieve an inverse growth - associated production of a foreign protein, beta-galactosidase.

Protein synthesis in mammalian cells can be observed in two strikingly different patterns: 1) production of monoclonal antibodies in hybridoma cultures is typically inverse growth associated and 2) production of most therapeutic glycoproteins in recombinant mammalian cell cultures is found to be growth associated. Production of monoclonal antibodies has been easily maximized by culturing hybridoma cells at very low growth rates in high cell density fed- batch or perfusion bioreactors. Applying the same bioreactor techniques to recombinant mammalian cell cultures results in drastically reduced production rates due to their growth associated production kinetics. Optimization of such growth associated production requires high cell growth conditions, such as in repeated batch cultures or chemostat cultures with attendant excess biomass synthesis. Our recent research has demonstrated that this growth associated production in recombinant Chinese hamster ovary (CHO) cells is related to the S (DNA synthesis)-phase specific production due to the SV40 early promoter commonly used for driving the foreign gene expression. Using the stably transfected CHO cell lines synthesizing an intracellular reporter protein under the control of SV40 early promoter, we have recently demonstrated in batch and continuous cultures that the product synthesis is growth associated. We have now replaced this S-phase specific promoter in new expression vectors with the adenovirus major late promoter which was found to be active primarily in the G1-phase and is expected to yield the desirable inverse growth associated production behavior. Our results in repeated batch cultures show that the protein synthesis kinetics in this resulting CHO cell line is indeed inverse growth associated. Results from continuous and high cell density perfusion culture experiments also indicate a strong inverse growth associated protein synthesis. The bioreactor optimization with this desirable inverse growth associated production behavior would be much simpler than bioreactor operation for cells with growth associated production.

Fed-batch culture of recombinant NS0 myeloma cells with high monoclonal antibody production

An amplified NS0 cell line transfected with a vector expressing a humanized monoclonal antibody (MAb) against CD-18 and glutamine synthetase (GS) was cultivated in a 1.5 L fed-batch culture using a serum-free, glutamine-free medium. Concentrated solutions of key nutrient components were fed periodically using a simple feeding control strategy. Feeding amounts were adjusted daily based on the integral of viable cell concentration over time (IVC) and assumed constant specific nutrient consumption rates or yields to maintain concentrations of the key nutrient components around their initial levels. On-line oxygen uptake rate (OUR) measurement was used to aid empirically the adjustment of the feeding time points and amounts by inferring time points of nutrient depletion. Through effective nutritional control, both cell growth phase and culture lifetime were prolonged significantly, resulting in a maximal viable cell concentration of 6.6 x 10(9) cells/L and a final IVC of 1.6 x 10(12) cells-h/L at 672 h. The final MAb concentration reached more than 2.7 g/L. In this fed-batch culture, cellular metabolism shifts were repeatedly observed. Accompanying the culture phase transition from the exponential growth to the stationary phase, lactate, which was produced in the exponential growth phase, became consumed. The time point at which this metabolism shift occurred corresponded to that of rapid decrease of OUR, which most likely was caused by nutrient depletion. This transition coincided with the onset of ammonia, glutamate and glutamine accumulation. With removal of the nutrient depletion by increasing the daily nutrient feeding amount, OUR recovered and viable cell concentration increased, while cell metabolism shifted again. Instead of consumption, lactate became produced again. These results suggest close relationships among nutrient depletion, cell metabolism transition, and cell death. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 55: 783-792, 1997.

Kinetics and modeling of GM-CSF production by recombinant yeast in a three-phase fluidized bed bioreactor

Continuous production of a recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) by Saccharomyces cerevisiae strain XV2181 (a/a, Trp 1) containing plasmid palphaADH2 and immobilized on porous glass beads in a fluidized bed bioreactor was studied. Kinetic models for plasmid stability, cell growth, and protein production in the three-phase fluidized bed bioreactor were developed and used to study the effects of solid loading or cell immobilization on plasmid stability and recombinant protein production. With increasing cell immobilization or solid loading in the bioreactor, plasmid stability and protein production improved significantly. The improvements could be attributed to the decreased theta value, which is the plasmid loss probability during cell division and is an indication of segregational instability of the recombinant cell, and the increased alpha value, which is the ratio of the specific growth rate of a plasmid-carrying cell to that of a plasmid-free cell and is indicative of competitive stability of the recombinant cell culture. theta decreased from 0.552 to 0.042 and alpha increased from 0.351 to 0.991 when solid loading in the bioreactor was increased from 5% (v/v) to 33%. The model simulation also showed that the specific growth rate of cells in the bioreactor was lower at higher solid loading. This indicated that there was significant mass transfer limitation, particularly for oxygen transfer, when the total cell density in the bioreactor was high at high solid loading. (c) 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 470-477, 1997.

Kinetics and modeling of GM‐CSF production by recombinant yeast in a three‐phase fluidized bed bioreactor

Continuous production of a recombinant murine granulocyte-macrophage colony-stimulating factor (GM-CSF) by Saccharomyces cerevisiae strain XV2181 (a/a, Trp 1) containing plasmid pαADH2 and immobilized on porous glass beads in a fluidized bed bioreactor was studied. Kinetic models for plasmid stability, cell growth, and protein production in the three-phase fluidized bed bioreactor were developed and used to study the effects of solid loading or cell immobilization on plasmid stability and recombinant protein production. With increasing cell immobilization or solid loading in the bioreactor, plasmid stability and protein production improved significantly. The improvements could be attributed to the decreased θ value, which is the plasmid loss probability during cell division and is an indication of segregational instability of the recombinant cell, and the increased α value, which is the ratio of the specific growth rate of a plasmid-carrying cell to that of a plasmid-free cell and is indicative of competitive stability of the recombinant cell culture. θ decreased from 0.552 to 0.042 and α increased from 0.351 to 0.991 when solid loading in the bioreactor was increased from 5% (v/v) to 33%. The model simulation also showed that the specific growth rate of cells in the bioreactor was lower at higher solid loading. This indicated that there was significant mass transfer limitation, particularly for oxygen transfer, when the total cell density in the bioreactor was high at high solid loading. © 1997 John Wiley & Sons, Inc. Biotechnol Bioeng 53: 470–477, 1997.

Changes in monoclonal antibody productivity of recombinant BHK cells immobilized in collagen gel particles.

Animal cell perfusion high density culture is often adopted for the production of biologicals in industry. In high density culture sometimes the productivity of biologicals has been found to be enhanced. Especially in immobilized animal cell culture, significant increase in the productivity has been reported. We have found that the specific monoclonal antibody (MAb) productivity of an immobilized hybridoma cell is enhanced more than double. Several examples of enhancing productivities have been also shown by collagen immobilized cells. Immobilized cells involve some different points from non-immobilized cells in high density culture: In immobilized culture, some cells are contacted together, resulting in locally much higher cell concentration more than 10(8) cells/ml. Information originating from a cell can be easily transduced to the others in immobilized culture because the distance between cells is much nearer. Here we have performed collagen gel immobilized culture of recombinant BHK cells which produce a human IgG monoclonal antibody in a protein-free medium for more than three months. In this high density culture a stabilized monoclonal antibody production was found with around 8 times higher specific monoclonal antibody productivity compared with that in a batch serum containing culture. No higher MAb productivity was observed using a conditioned medium which was obtained from the high density culture, indicating that no components secreted from the immobilized cells work for enhancing monoclonal antibody production. The MAb productivity by the non-immobilized cells obtained by dissolving collagen using a collagenase gradually decreased and returned to the original level in the batch culture using a fresh medium. This suggests that the direct contact of the cells or a very close distance between the cells has something to do with the enhancement of the MAb productivity, and the higher productivity is kept for a while in each cell after they are drawn apart.

Feeding of nutrients delays apoptotic death in fed-batch cultures of recombinant NSO myeloma cells

The addition of concentrated nutrient solutions in fed-batch cultures of recombinant GS-NSO cells delays the onset of apoptosis by 24 to 48 hours and decreases the specific rate of apoptotic death approximately two-fold. This decrease in apoptosis appears primarily responsible for the increase in culture longevity that results in five- to ten-fold increases in final product concentrations in fed-batch cultures.

Foreign protein expression from S phase specific promoters in continuous cultures of recombinant CHO cells

Foreign protein expression from the commonly used SV40 promoter has been found to be primarily during the S-phase of the cell cycle. Simple mathematical models with this cell cycle phase dependent expression of foreign protein suggest that the specific production rate will be proportional to the cell growth rate, which is particularly disadvantageous in high cell density fed-batch or perfusion bioreactors. In this study we investigate this predicted relationship between the production rate and growth rate by culturing recombinant CHO cells in a continuous suspension bioreactor. One CHO cell line, GS-26, has been stably transfected with the plasmid pSVgal, which contains the E. coli lac Z gene under the control of the SV40 promoter. This GS-26 cell line was grown in suspension cultures over a range of specific growth rates in batch and continuous modes. The intracellular β-galactosidase activity was assayed using a standard spectrophotometric method after breaking the cells open and releasing the enzyme. A strong growth associated relationship is found between the intracellular β-galactosidase content and the specific growth rate in batch and continuous cultures, as predicted.

A Method for Purification of Clostridium perfringens Phospholipase C from Recombinant Bacillus subtilis Cells

We developed a method to purify Clostridium perfringens phospholipase C from a culture of recombinant Bacillus subtilis cells. This method consists of three purification steps, and it allowed us to obtain 6.2 mg of pure phospholipase C from 800 ml of culture.

Estimating segregational plasmid instability in recombinant cell cultures: A generalized approach

A generalized methodology for estimation of the relative segregation rate, ( p), in a recombinant cell culture has been presented that does not require the a priori assumption of a constant ‘ p’. Moreover, measurement of no other variable in addition to those conventionally monitored, viz. overall culture concentration and fraction plasmid-bearing cells is necessary.

Use of on-line gas analysis to monitor recombinant mammalian cell cultures.

The development of a system capable of accurately measuring the oxygen uptake and carbon dioxide production rates during mammalian cell cultures is described. A detailed study of the specifications of the various components used in the system for the measurement of gas flow rates and composition, coupled with the validation of the system independent of the bioreactor was carried out. The aim of this study was to identify and eliminate where possible the errors controlling the accuracy of determination of gaseous metabolic rates. This study showed the importance of controlling the temperature of gaseous oxygen entering the system. With such temperature control, it was possible to obtain data with an accuracy of +/- 5% at the 95% confidence level. Another source of error, the use of bi-carbonate buffer, was studied. A mathematical model was used to compensate for the affect of such buffers on the determination of carbon dioxide production rates. The use of the system for the continuous determination of gaseous metabolism during the growth and production phase for recombinant CHO cell cultures is described.

Isolation, Characterization, and Proteolysis of Human Prosaposin, the Precursor of Saposins (Sphingolipid Activator Proteins)

Prosaposin contains separate domains in tandem for four saposins, A, B, C, and D. These mature saposins are produced by limited proteolysis of prosaposin. They are involved in lysosomal hydrolysis of GM1 ganglioside, gluco- and galactocerebrosides, sulfatides, and sphingomyelin and other sphingolipids. Prosaposin also exists as a secretory protein in body fluids. In this investigation prosaposin was expressed in Spodoptera frugiperda cells (Sf9) by infection with baculovirus containing a full length cDNA coding for human prosaposin. Prosaposin was isolated and purified from spent culture medium of the recombinant Sf9 cell cultures as well as from human seminal plasma and milk. From sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the molecular weight of both native human prosaposins is estimated to be 66 kDa and that of recombinant prosaposin as 58 kDa. Deglycosylation of native and recombinant prosaposins yielded a protein with a molecular weight of 54 kDa and isoelectric point of 5.4. The N-terminal sequence of both native and recombinant prosaposins was identical (G-P-V-L-L-G-L-K). Like mature saposins, all prosaposins possessed stimulative activity for cerebroside β-glucosidase (saposins A and C activity), GM1 ganglioside β-galactosidase (saposin B activity), and sphingomyelinase (saposin D activity) but not sulfatide sulfatase (saposin B activity). Partially proteolyzed products derived from prosaposins were isolated and identified. From seminal plasma, two proteins of 48 and 29 kDa and from Sf9 culture media, two proteins of 39 and 26 kDa were characterized. N-terminal amino acid sequencing and Western blot analysis of each protein indicated that the 39- and 48-kDa proteins are cleavage products containing domains for saposins B, C, and D (trisaposins), and the 26- and 29-kDa proteins are cleavage products containing domains for saposins C and D (disaposin). These observations suggest that proteolysis of prosaposin in these tissues occurs sequentially from the N-terminal region. Proteins involved in the initial proteolysis of prosaposin were partially characterized in human testis.

Investigation of subpopulation heterogeneity and plasmid stability in recombinant escherichia coli via a simple segregated model

Many microbial and cell cultures exhibit phenomena that can best be described using a segregated modeling approach. Heterogeneties are more marked in recombinant cell cultures because subpopulations, which often exhibit different growth and productivity characteristics, are more easily identified by selective markers. A simple segregated mathematical model that simulates the growth of recombinant Escherichia coli cells is developed. Subpopulations of different growth rate, plasmid replication rate, and plasmid segregation probability are explicitly considered. Results indicate that a third mechanism of plasmid instability, referred to here as a "downward selective pressure," is significant when describing plasmid loss in batch and chemostat cultures. Also, the model agrees well with experimental data from cultures under antibiotic selective pressure. Finally, model simulations of chemostat cultures reveal the importance of initial conditions on culture stability and the possible presence of nonrandom partitioning functions.

Effect of amplification of dhfr and lac Z genes on growth and beta-galactosidase expression in suspension cultures of recombinant CHO cells.

Studies were conducted to characterize the effect of gene amplification and foreign gene expression on recombinant CHO cell growth. Chinese hamster ovary (CHO) cells were transfected with an expression vector containing the gene for dihydrofolate reductase (dhfr) and the gene for human beta-interferon (beta-IFN) or the lac Z gene which codes for beta-galactosidase (beta-gal). The recombinant genes in these CHO cells were amplified stepwise by growth in 0, 10(-7), and 10(-6) M methotrexate (MTX), and the beta-gal expressing cells were adapted to suspension culture. Flow cytometric methods (FCM) were used to measure the distribution of amplified dhfr gene content and foreign beta-gal gene expression in the cell populations. A biochemical assay for beta-gal was also used. Beta-gal expression was found to increase with increasing gene amplification. The growth rate of recombinant CHO cells at 10(-7) M MTX was found to be 20% lower than that of recombinant CHO cells in MTX-free medium, and the cell growth rate at 10(-6) M MTX was 20% lower than that of recombinant CHO cells at 10(-7) M MTX. There was no effect of 10(-5) M MTX on the growth of CHO-DG44 (dhfr-) cells. The reduction of growth rate in recombinant CHO cells is therefore thought to be mainly due to the effect of dhfr and foreign gene amplification and increased beta-galactosidase expression.

CORRIGENDUM

DNA and Cell BiologyVol. 10, No. 5 CORRIGENDUMThe P450 Superfamily: Update on New Sequences, Gene Mapping, and Recommended NomenclatureDANIEL W. NEBERT, DAVID R. NELSON, MINOR J. COON, RONALD W. ESTABROOK, RENE FEYEREISEN, YOSHIAKI FUJII-KURIYAMA, FRANK J. GONZALEZ, F. PETER GUENGERICH, IRWIN C. GUNSALUS, ERIC F. JOHNSON, JOHN C. LOPER, RYO SATO, MICHAEL R. WATERMAN, and DAVID J. WAXMANDANIEL W. NEBERTSearch for more papers by this author, DAVID R. NELSONSearch for more papers by this author, MINOR J. COONSearch for more papers by this author, RONALD W. ESTABROOKSearch for more papers by this author, RENE FEYEREISENSearch for more papers by this author, YOSHIAKI FUJII-KURIYAMASearch for more papers by this author, FRANK J. GONZALEZSearch for more papers by this author, F. PETER GUENGERICHSearch for more papers by this author, IRWIN C. GUNSALUSSearch for more papers by this author, ERIC F. JOHNSONSearch for more papers by this author, JOHN C. LOPERSearch for more papers by this author, RYO SATOSearch for more papers by this author, MICHAEL R. WATERMANSearch for more papers by this author, and DAVID J. WAXMANSearch for more papers by this authorPublished Online:25 Mar 2009https://doi.org/10.1089/dna.1991.10.397AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "CORRIGENDUM." , 10(5), pp. 397–398FiguresReferencesRelatedDetailsCited byEffects of Andrographis paniculata extract and Andrographolide on hepatic cytochrome P450 mRNA expression and monooxygenase activities after in vivo administration to rats and in vitro in rat and human hepatocyte culturesChemico-Biological Interactions, Vol. 179, No. 2-3Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis paniculata extract and andrographolideJournal of Ethnopharmacology, Vol. 115, No. 3Impact of Andrographis paniculata crude extract on mouse hepatic cytochrome P450 enzymesJournal of Ethnopharmacology, Vol. 105, No. 3Application of the luciferase recombinant cell culture bioassay system for the analysis of polycyclic aromatic hydrocarbonsEnvironmental Toxicology and Chemistry, Vol. 21, No. 10Application of the luciferase cell culture bioassay for the detection of refined petroleum productsMarine Pollution Bulletin, Vol. 44, No. 10Comparisons of catalytic selectivity of cytochrome P450 subfamily enzymes from different speciesChemico-Biological Interactions, Vol. 106, No. 3An Introduction to Drug Disposition: The Basic Principles of Absorption, Distribution, Metabolism, and Excretion2 July 2016 | Toxicologic Pathology, Vol. 23, No. 2Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man.6 July 2012 | British Journal of Clinical Pharmacology, Vol. 35, No. 4A theoretical study on the oxidative metabolism of 4-chloroacetanilide by cytochrome P450: Alternative mechanisms for migration of 4-substituents during enzymatic oxidation2 September 2010 | Recueil des Travaux Chimiques des Pays-Bas, Vol. 112, No. 2Molecular cloning of cDNA encoding the phenol/aryl form of sulfotransferase (mSTpl) from mouse liverBiochimica et Biophysica Acta (BBA) - Gene Structure and Expression, Vol. 1171, No. 3Generalized cytochrome P450-mediated oxidation and oxygenation reactions in aromatic substrates with activated N-H, O-H, C-H, or S-H substituents22 September 2008 | Xenobiotica, Vol. 23, No. 6Cytochromes P450: Their Active-Site Structure and Mechanism of Oxidation22 September 2008 | Drug Metabolism Reviews, Vol. 25, No. 3The UDP Glucuronosyltransferase Gene Super family: Suggested Nomenclature Based on Evolutionary Divergence BRIAN BURCHELL, DANIEL W. NEBERT, DAVID R. NELSON, KARL W. BOCK, TAKASHI IYANAGI, PETER L.M. JANSEN, DORON LANCET, GERARD J. MULDER, JAYANTA ROY CHOWDHURY, GERARD SIEST, THOMAS R. TEPHLY, and PETER I. MACKENZIE25 March 2009 | DNA and Cell Biology, Vol. 10, No. 7 Volume 10Issue 5Jun 1991 To cite this article:DANIEL W. NEBERT, DAVID R. NELSON, MINOR J. COON, RONALD W. ESTABROOK, RENE FEYEREISEN, YOSHIAKI FUJII-KURIYAMA, FRANK J. GONZALEZ, F. PETER GUENGERICH, IRWIN C. GUNSALUS, ERIC F. JOHNSON, JOHN C. LOPER, RYO SATO, MICHAEL R. WATERMAN, and DAVID J. WAXMAN.CORRIGENDUM.DNA and Cell Biology.Jun 1991.397-398.http://doi.org/10.1089/dna.1991.10.397Published in Volume: 10 Issue 5: March 25, 2009PDF download