Abstract:
:The polyglutamation kinetics of methotrexate (MTX) in MCF-7 human breast cancer cells have been formulated mathematically. The model takes account of glutamation and hydrolysis kinetics up through the pentaglutamate level, increased synthesis of dihydrofolate reductase following exposure to drug, reversible tight-binding to reductase, and membrane transport of polyglutamates. The glutamation, hydrolysis, and efflux parameters have been determined from fits to experimental MTX polyglutamate uptake and efflux data. The preferred substrate for folypolyglutamyl synthase in the intact cell appears to be MTX diglutamate, on average being two to three times as reactive as either the parent drug or the triglutamate. Hydrolysis rate constants range from 0.03 to 0.19 h-1, but no clear trend with chain length is observable given the large uncertainty of each parameter estimate. However, the efflux of MTX polyglutamates from MCF-7 cells does show a trend with chain length decreasing with increasing length as expected. The best characteristic time of MTX diglutamate efflux is 4.1 h, about one-third that of the higher polyglutamate species, in agreement with observations on the MDA.MB.436 breast cancer cell line. The model shows quantitative agreement with the fraction of MTX polyglutamates found still to be bound to reductase in MCF-7 cells following 24 h of efflux, and qualitative agreement with the time dependence of bound MTX-polyglutamate concentration profiles obtained on the ZR-75 breast cancer line.
journal_name
Arch Biochem Biophysjournal_title
Archives of biochemistry and biophysicsauthors
Morrison PF,Allegra CJdoi
10.1016/0003-9861(87)90143-3subject
Has Abstractpub_date
1987-05-01 00:00:00pages
597-610issue
2eissn
0003-9861issn
1096-0384pii
0003-9861(87)90143-3journal_volume
254pub_type
杂志文章abstract::Methyl acetyl phosphate, which was originally synthesized as a site-specific reagent for hydroxybutyrate dehydrogenase [R. Kluger and W.-C. Tsui (1980) J. Org. Chem. 45, 2723], also has an affinity for the binding site for 2,3-diphosphoglycerate in hemoglobin. Three residues in or near this cleft between the beta-chai...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/0003-9861(86)90648-x
更新日期:1986-02-01 00:00:00
abstract::The effect of glutathione (GSH) on the superoxide-sensitive [4Fe-4S]-containing aconitase of Escherichia coli was explored. A mutant deficient in GSH biosynthesis, designated gshA, grew slower in a defined medium than did the parental strain and this effect was more pronounced when succinate was supplied as the carbon...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.1993.1120
更新日期:1993-02-15 00:00:00
abstract::The binding of Toxin A isolated from Clostridium difficile to rabbit erythrocyte glycolipids has been studied. Total lipid extracts from rabbit erythrocytes were subjected to thin-layer chromatography and toxin-binding glycolipids detected by using 125I-labeled Toxin A in a direct binding overlay technique. Two major ...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/0003-9861(87)90561-3
更新日期:1987-08-15 00:00:00
abstract::Activation of the delta-isoform of protein kinase C (deltaPKC) by certain conditions of oxidative stress results in translocation of the kinase to the mitochondria leading to release of cytochrome c and the induction of apoptosis. In the current study, the effects of myocardial reperfusion-induced deltaPKC translocati...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/j.abb.2005.05.007
更新日期:2005-07-15 00:00:00
abstract::The mitochondrial ATP synthase/ATPase (F0F1 ATPase) is perhaps the most complex enzyme known. In animal systems it consists of a minimum of 11 different polypeptide chains, 10 (or more) of which appear to be essential for function, and 1 called the "ATPase inhibitor peptide" which is involved in regulation. Recent stu...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章,评审
doi:10.1016/0003-9861(86)90695-8
更新日期:1986-10-01 00:00:00
abstract::The association of myelin basic protein charge isomers with the lipid part of the myelin membrane was investigated at the microscopic (molecular) level in a model membrane system, using optical waveguide lightmode spectrometry to determine with high precision the kinetics of association and dissociation to planar phos...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/j.abb.2003.09.020
更新日期:2003-11-15 00:00:00
abstract::Proteins containing the post-translationally modified amino acid L-3,4-dihydroxyphenylalanine (DOPA) undergo autosclerotization as a means of assuring cohesive resilience in many structural matrices found in nature. To explore the chemical mechanism of sclerotization, we examined the oxidation products of relatively s...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/0003-9861(91)90323-b
更新日期:1991-02-15 00:00:00
abstract::To assess the indirect effects of snake venom metalloproteinases (SVMP) on host tissue local necrosis, we investigated the effect of the SVMP jararhagin on the gene expression profiles of human fibroblasts in vitro and mouse tissue in vivo. Two functional classes of up-regulated proteins, cell death and inflammatory d...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/j.abb.2005.06.007
更新日期:2005-09-01 00:00:00
abstract::Elevation of cytosolic level of Ca(2+) was measured by spatial screening of freshly isolated dorsal root ganglion neurons loaded with Fura-2AM after subjecting them to a moderate hypoxic solution (pO(2)=10-40 mmHg). Short exposure of neurons to hypoxia resulted in a reversible elevation of intracellular Ca(2+) to abou...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/s0003-9861(02)00682-3
更新日期:2003-02-15 00:00:00
abstract::Nitric oxide (.NO) and peroxynitrite (ONOO-) inhibit enzymes that depend on metal cofactors or oxidizable amino acids for activity. Since xanthine oxidase (XO) is a 2(2Fe2S) enzyme having essential sulfhydryl groups linked with Mo-pterin cofactor function, the influence of .NO and ONOO- on purified bovine XO was deter...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.1998.0675
更新日期:1998-07-01 00:00:00
abstract::Previous work from this laboratory indicated that the N-terminus of recombinant human cytochrome P450 (P450) 1A2 expressed in Escherichia coli is blocked (P. Sandhu, Z. Guo, T. Baba, M. V. Martin, R. H. Tukey, and F. P. Guengerich, (1994) Arch. Biochem. Biophys. 30, 168 -177). A modification of this construct was done...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.1996.0086
更新日期:1996-03-01 00:00:00
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.2000.2088
更新日期:2000-12-15 00:00:00
abstract::Through linking inducible cyclooxygenase (COX)-2 with microsomal prostaglandin E2 (PGE2) synthase-1 (mPGES-1), a Single-Chain Enzyme Complex (SCEC, COX-2-10aa-mPGES-1) was engineered to mimic a specific inflammatory PGE2 biosynthesis from omega-6 fatty acid, arachidonic acid (AA), by eliminating involvements of non-in...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/j.abb.2016.04.011
更新日期:2016-08-01 00:00:00
abstract::The effect of modulating AP-1 activity on the levels of induced erythroid and megakaryocytic differentiation of the erythroleukemia cell line K562 was examined. Cells were stably transfected with expression vectors encoding either a tetracycline-responsive dominant negative c-Jun (JunDN) or a hybrid Raf protein induci...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.1998.0597
更新日期:1998-04-15 00:00:00
abstract::The stability of the Glossoscolex paulistus hemoglobin (HbGp), in two iron oxidation states (and three forms), as monitored by optical absorption, fluorescence emission and circular dichroism (CD) spectroscopies, in the presence of the chaotropic agent urea, is studied. HbGp oligomeric dissociation, denaturation and i...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/j.abb.2012.01.007
更新日期:2012-03-01 00:00:00
abstract::Studies have followed the turbidity (OD400 nm) of beta-casein (CN) as temperature (T) increased from 4 to 37 degrees C. Native non-phosphorylated beta-CN showed a turbidity increase above 25 degrees C and precipitated at about 22 degrees C in 5mM Ca+2. These patterns were reproducible upon T-cycling while those of rec...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/j.abb.2006.07.008
更新日期:2006-10-01 00:00:00
abstract::Several substrate analogs were tested for their ability to inhibit bovine pancreatic asparagine synthetase. Of the substrate analogs tested both 6-diazo-5-oxo-L-norleucine (DON) and 5-chloro-4-oxo-L-norvaline (CONV) were shown to inhibit the enzyme strongly. DON inhibited the glutaminase and glutamine-dependent aspara...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/0003-9861(91)90276-o
更新日期:1991-01-01 00:00:00
abstract::High-Mr and monomeric adenosine deaminase were injected intravenously into the rabbit. The rates of clearance and sites of uptake of the enzymes were compared. Calf intestinal mucosa served as the source of monomeric adenosine deaminase. High-Mr enzymes were assembled in vitro from the calf enzyme and adenosine deamin...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/0003-9861(84)90097-3
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journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/0003-9861(88)90036-7
更新日期:1988-11-15 00:00:00
abstract::Sucrose-phosphate synthase (SPS; EC 2.4.1.14) is regulated in part by reversible protein phosphorylation. When dephospho-SPS is partially purified from illuminated spinach leaves and incubated with [gamma-32P]ATP the enzyme is phosphorylated by a copurifying protein kinase. In this report, 32P-phosphopeptides from try...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.1993.1586
更新日期:1993-12-01 00:00:00
abstract::Conversion of a steroid receptor complex from the 8 S to the 4S form results in new interactions between the steroid and the receptor and/or formation of new intra-protein bonds within the receptor molecule itself. These bonds must be broken before the steroid is released. In order to localize these newly formed inter...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/0003-9861(91)90310-f
更新日期:1991-02-01 00:00:00
abstract::We explored furin substrate requirements in addition to the motif R-X-K/R-R using synthetic fluorescent resonance energy transfer (FRET) decapeptides. These decapeptides were derived from furin cleavage sites in viral coat glycoproteins and human and bacterial protein precursors. The hydrolysis by furin of most substr...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/j.abb.2009.05.013
更新日期:2009-07-15 00:00:00
abstract::We propose that adverse effects of the antibiotic metronidazole may be due, wholly or in part, to its conversion to a thiamine analog and consequent vitamin B1 antagonism. Consistent with this hypothesis, the drug is accepted as a substrate for the thiaminase (EC 2.5.1.2) elaborated as an exoenzyme by the human gut fl...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/0003-9861(87)90577-7
更新日期:1987-09-01 00:00:00
abstract::Actinomycin D (act-D) anchors itself into DNA-base pairs by intercalation and thereby inhibits mRNA synthesis. It has been well established that act-D elicits apoptosis in various cell types involving endothelial cells. However, the regulatory mechanisms of actinomycin D-induced apoptotic cell death still remain uncle...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/j.abb.2004.03.028
更新日期:2004-05-15 00:00:00
abstract::Salicylhydroxamic acid reductase, which catalyzes the reduction of salicylhydroxamic acid to salicylamide, was purified from rat liver cytosol. The purification procedure consisted of fractionation with ammonium sulfate, chromatography with Phenyl-Toyopearl 650, DEAE-cellulose, hydroxyapatite, and Sephadex G-200, and ...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.1993.1223
更新日期:1993-05-01 00:00:00
abstract::Cofactor and tryptophan accessibility of the 65-kDa form of rat brain glutamate decarboxylase (GAD) was investigated by fluorescence quenching measurements using acrylamide, I-, and Cs+ as the quenchers. Trp residues were partially exposed to solvent. I- was less able and Cs+ was more able to quench the fluorescence o...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1006/abbi.2001.2466
更新日期:2001-08-15 00:00:00
abstract::The biosynthesis of one riboflavin molecule requires one molecule of GTP and two molecules of ribulose 5-phosphate as substrates. GTP is hydrolytically opened, converted into 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione by a sequence of deamination, side chain reduction and dephosphorylation. Condensation with 3,...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章,评审
doi:10.1016/j.abb.2008.02.008
更新日期:2008-06-15 00:00:00
abstract::Homogeneous preparations of fructose-1,6-bisphosphatase from mouse, man, rabbit, pig, and rat were tested as substrates for cyclic AMP-dependent protein kinase. Up to 1 mol of [32P]phosphate per mole enzyme subunit was incorporated into fructose-1,6-bisphosphatase from pig and rabbit liver, which should be compared wi...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/0003-9861(88)90164-6
更新日期:1988-04-01 00:00:00
abstract::The in vivo turnover of several rat liver microsomal proteins was studied using techniques designed to maximize antibody recognition specificity and minimize reutilization of radioactive labels. The kinetics of degradation of seven cytochrome P-450 isozymes, NADPH-cytochrome P-450 reductase, and epoxide hydrolase were...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/0003-9861(84)90257-1
更新日期:1984-11-15 00:00:00
abstract::In this work we demonstrate that aldose reductase (AR) interacts directly with tubulin and, was subjected to microtubule formation conditions, enzymatic AR activity increased more than sixfold. Since AR interacts mainly with tubulin that has 3-nitro-tyrosine in its carboxy-terminal, we evaluated whether tyrosine and o...
journal_title:Archives of biochemistry and biophysics
pub_type: 杂志文章
doi:10.1016/j.abb.2018.07.009
更新日期:2018-09-15 00:00:00