Substrates multiple enzyme induction. Medical search. Frequent questions

Table 2 provides definitions of substrates, inhibitors, and inducers for CYP-based metabolism and Table 3 provides definitions of inhibitors and substrates for drug transporter systems. (fda.gov)
Cytochrome P4503A4 (CYP3A4) is the major drug-metabolizing enzyme in human liver and is responsible for the clearance of many commonly used drugs, including benzodiazepines, statins, calcium channel blockers, and HIV protease inhibitors. (aspetjournals.org)
Inhibitors of hepatic microsomal enzymes, such as erythromycin, clarithromycin, and cimetidine, increase carbamazepine levels and may cause toxicity. (medscape.com)
Objectives: The objective of this study was to explore potential drug-drug/food interactions of ciprofloxacin and grapefruit juice, known hepatic cytochrome P450 (CYP) 1A2 inhibitors, on single-dose oral pharmacokinetics of riluzole, a substrate of CYP 1A2 enzymes. (researchgate.net)
A search of the University of Washington Drug-Drug Interaction Database was conducted to identify a clinically relevant weak, moderate, and strong inhibitor for selective substrates of CYP1A2, CYP2C8, CYP2C9, CYP2C19, and CYP2D6, resulting in 18 inhibitors for in vitro characterization against 119 clinical interaction studies. (aspetjournals.org)
Cholinesterases (ChEs) display a hysteretic behavior with certain substrates and inhibitors. (msu.ru)
However, the accepted view that proteins are in equilibrium between preexisting functional and non-functional conformers, and that binding of a ligand to the functional form shifts equilibrium towards the functional conformation, suggests that slow equilibrium between two conformational states of these enzymes may have a regulatory function in damping out the response to certain ligands and irreversible inhibitors. (msu.ru)
Our laboratory has combined structural analysis with functional studies to define the molecular determinants of the interaction of ligands (substrates and inhibitors) with COX-2. (vanderbilt.edu)
Comparative analysis of the effect of site-directed mutation of active site residues on the binding of substrates and inhibitors to COX-1 and COX-2 led us to hypothesize that neutral derivatives of esters and amides would bind selectively to COX-2. (vanderbilt.edu)
DrugInteractions Cinacalcet is metabolized in part by cytochrome P450 isoenzyme 3A4, so inhibitors of this enzyme. (spiritsong.org)

17 (2004), pp. 1706-1715 T. Li, R. Santockyte, R.F. Shen, E. Tekle, G. Wang, D.C. Yang and P.B. Chock, A general approach for investigating enzymatic pathways and substrates for ubiquitin-like modifiers, Arch. (wikipedia.org)
Induction of canonical autophagy is mainly controlled by the AKT/mTOR and AMPK signaling pathways and relies on the activation and assembly of two macromolecular complexes, the ATG1/ULK1 and the Class III phosphatidylinositol 3-kinase (PI3K) complex (Figure 1 ) [ 5 ]. (hindawi.com)
In addition, induction of enzymes can affect enzymes in endogenous metabolic pathways, which can subsequently affect bone, gonadal steroid, and lipid metabolism. (medscape.com)
Once activated, p53 coordinates multiple downstream pathways, thereby maintaining the homeostasis of the host cell or organism (if the stress is mild, transient, and repairable) or eliminating damaged cells (if the stress is acute, prolonged, and difficult to resist). (nature.com)
The products of both pathways of oxygenation are substrates for metabolizing enzymes that generate a panoply of lipid mediators. (vanderbilt.edu)
Minor significance for acetaminophen due to multiple pathways of the drug's metabolism. (interactionsguide.com)

Cytochrome P-450 (CYP) enzymes are responsible for the metabolism of many drugs, and transporter systems allow for movement of many drugs across cell membranes. (fda.gov)
In previous issues of Pharmacy Times , we discussed the cytochrome P450 (CYP450) enzymes CYP1A2 and CYP2C9. (pharmacytimes.com)
Cytochrome P4503A4 (CYP3A4) is the principal drug-metabolizing enzyme in human liver. (aspetjournals.org)
Armodafinil is a stimulant whose indications include obstructive sleep apnea, narcolepsy, and shift work sleep disorder, and like carbamazepine, it is an inducer of and substrate for cytochrome P450 (CYP3A4). (medscape.com)
Inactivation of Cytochrome P450 (CYP450) enzymes can lead to significant increases in exposure of comedicants. (aspetjournals.org)
Human cytochrome P450 (CYP) 2C enzymes metabolize ∼30% of clinically prescribed drugs and various environmental chemicals. (aspetjournals.org)

CYP2C8, an important member of this subfamily, metabolizes the anticancer drug paclitaxel, certain antidiabetic drugs, and endogenous substrates, including arachidonic acid, to physiologically active epoxyeicosatrienoic acids. (aspetjournals.org)
Our laboratory has a long-standing interest in enzymes of arachidonic acid oxygenation. (vanderbilt.edu)

The purpose of the current studies was to characterize the effect of known inducers on CYP3A4 in Fa2N-4 cells, and to determine whether these in vitro data could reliably project the magnitude of DDIs caused by induction. (aspetjournals.org)

In this fish, we also investigated the expression of CYP3A79 and its susceptibility to induction by various compounds including clotrimazole and dehydroepiandrosterone, two strong ligands of zebrafish PXR. (unipi.it)

We followed up on one pathway, finding that Set1-dependent H3K4 methylation primarily acts as a gene repressor during multiple stresses, specifically at genes involved in ribosome biosynthesis. (harvard.edu)
In some plant species, AA is the substrate for the biosynthesis of oxalate and tartrate (Smirnoff and Wheeler, 2000). (deepdyve.com)

Drug-drug interactions (DDIs) caused by induction of CYP3A4 can result in decreased exposure to coadministered drugs, with potential loss of efficacy. (aspetjournals.org)
In Fa2N-4 cells, all 18 positive controls produced greater than 2-fold maximal CYP3A4 induction, and all 6 negative controls produced less than 1.5-fold maximal CYP3A4 induction. (aspetjournals.org)
Certain drugs can modulate the level of CYP3A4 activity, thereby causing changes in clearance of coadministered drugs that are CYP3A4 substrates. (aspetjournals.org)
Levels of CYP3A4 activity can be decreased by inhibition of enzyme activity, or increased by induction of new protein synthesis. (aspetjournals.org)
Changes in CYP3A4 activity, either through inhibition or induction, can result in potentially serious drug-drug interactions (DDIs). (aspetjournals.org)
Induction of CYP3A4 is thought to occur primarily through transcriptional activation of the gene. (aspetjournals.org)
There are several in vitro tools for assessment of CYP3A4 induction. (aspetjournals.org)
CYP3A4 expression can be evaluated by measuring enzymatic activity with a selective probe substrate or by measuring CYP3A4 mRNA. (aspetjournals.org)

The present study aimed to investigate the capability of the filamentous fungus Penicillium parvum 4-14 to enzymatically saccharify CBAX and reveal the fungal carbohydrate-active enzyme (CAZyme) repertoire by genome sequencing and secretome analysis. (biomedcentral.com)
The carbohydrate active enzymes - CAZymes - they use for the degradation of one specific polysaccharide are most often encoded for in genomic islands, meaning they are all very close together. (springernature.com)

Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. (biorxiv.org)

Many drugs are metabolized by more than one CYP450 enzyme, and this is especially true for CYP2C19, where it is often a secondary pathway. (pharmacytimes.com)
Many of the other drugs in Table 1 are metabolized primarily by other CYP450 enzymes. (pharmacytimes.com)

The initial hydrolysis step of PET is facilitated by an extracellular enzyme homologous to cutinases, but with an extraordinary capability to degrade PET, hence classified as a PETase (EC 3.1.1.101). (biomedcentral.com)
DNA sequence analysis revealed the THI5 gene to encode a second thiamine biosynthetic enzyme homologous to the product of the Schizosaccharomyces pombe gene nmtl. (le.ac.uk)

To achieve this goal, our laboratory developed a mass spectrometry-based assay detecting the presence of BoNT via its enzymatic activity on a peptide substrate. (cdc.gov)

This is particularly true for immobilized (membrane bound) enzymes where the local substrate and/or inhibitor concentrations depend on influx in crowded organellar systems, e.g. cholinergic synaptic clefts. (msu.ru)

Biphasic pseudo-first-order progressive inhibition of ChEs by certain carbamates and organophosphates also fits with a slow equilibrium between two reactive enzyme forms. (msu.ru)
Leukotrienes and prostaglandins are involved in multiple physiological and pathophysiological events, and inhibition of their action is the molecular basis for the pharmacological activities of several important drugs. (vanderbilt.edu)

Further, modeling and docking studies suggest DDL-701 interacts with the active site region of the PL pro enzyme and pilot pharmacokinetic studies indicate it is brain permeable. (biorxiv.org)

Bexarotene may induce metabolic enzymes and cause a reduction in the plasma concentrations of oral or other systemic hormonal contraceptives. (pdr.net)

These investigations provide more detailed information about the structural and functional basis for induction of mutation. (vanderbilt.edu)

Proteomics of these cultures revealed a heavy induction of the β-mannan PUL CAZymes on all our tested mannans, proving to us that the enzymes we had suspected to be a part of this degradation pathway actually were. (springernature.com)

In this issue, we will discuss CYP2C19?an enzyme whose activity varies depending upon important genetic differences among people and also is involved in some clinically important drug interactions. (pharmacytimes.com)
Enzyme induction interactions may be hard to detect clinically, since reduced drug effect may be interpreted as simply a lack of patient drug response. (pharmacytimes.com)

2004) V.G. Panse, U. Hardeland, T. Werner, B. Kuster and E. Hurt, A proteome-wide approach identifies sumoylated substrate proteins in yeast, J. Biol. (wikipedia.org)
280 (2005), pp. 4102-4110 Y. Zhao, S.W. Kwon, A. Anselmo, K. Kaur and M.A. White, Broad spectrum identification of cellular small ubiquitin-related modifier (SUMO) substrate proteins, J. Biol. (wikipedia.org)
The pyroptosis‑related proteins NLRP3, caspase‑1 and interleukin (IL)‑1β were also significantly elevated by I/R induction. (spandidos-publications.com)
During this evolutionary process, the experimental basis of the current (multiple) views on proteins have adapted to and exploited the unique physi- protein hydration, with an emphasis on the dynamic cal properties of liquid water (Eisenberg & Kauzmann aspects. (lu.se)

A further two, previously undescribed genes, encode a second small, 12kDa, stress-induced protein (HSP12) and a thiamine biosynthetic enzyme (THI4). (le.ac.uk)
Thus, although these genes show apparent coordinate induction they are regulated via different transcriptional control mechanisms. (le.ac.uk)
A very natural place to study gene detecting and metabolizing lactose, it is known that the overall regulation is in the metabolism of the cell, and then specifically in effect of expressing the lac genes in vain is a drop in the growth rate the regulation of genes that code for enzymes and transporter of as much as 5% [1,6]. (lu.se)
African swine fever virus (ASFV) is an acute and persistent swine virus with a high economic burden that encodes multiple genes to evade host immune response. (mdpi.com)
Alleles corresponding to seven TPS genes were amplified from ripe cone cDNA from multiple cultivars and subsequently functionally characterised by transient expression in planta . (biomedcentral.com)

Using antibodies specific for certain glyosidic linkages we could detect a suitable substrate for our enzymes in two different genera of diatoms, Chaetoceros and Coscinodiscus . (springernature.com)
Recently, publications reported the use of new peptide substrates to detect BoNT/A and /B with improved results over other peptide substrates. (cdc.gov)
In this work, we describe the results of testing the new substrates with multiple BoNT/A and /B subtypes and find that the substrates cannot detect many subtypes of BoNT/A and /B. (cdc.gov)

Carbamazepine stimulates the synthesis of many monooxygenase and conjugating enzymes, which leads to the metabolism of many medications. (medscape.com)
Multiple members of the CYP3A subfamily have been identified and intensively studied in mammals as they represent prominent CYP enzymes involved in drug metabolism. (unipi.it)
2016). AA also takes part in the regeneration of α-tocopherol (vitamin E) in photosynthetic membranes and participates in chloroplast metabolism as a cofactor for violaxanthin de-epoxidase, an enzyme involved in xanthophyll cycle-mediated photoprotection (Smirnoff and Wheeler, 2000). (deepdyve.com)

Table 1 also includes five other substances that interact with CYP enzymes and transporter systems (i.e. (fda.gov)
This website contains examples of drugs with CYP enzyme-based and transporter-based interactions but does not include drugs with other mechanisms leading to drug interactions (such as certain interactions affecting drug absorption (e.g., chelating agents, resin-based binders, interactions, and drugs that change gut pH), interactions affecting drug plasma protein binding, or pharmacodynamic interactions). (fda.gov)
The lac operon of E. coli is but one example of how enzyme and transporter production can be made conditional on the presence of a nutrient to catabolize. (lu.se)

Some drugs induce (stimulate) CYP2C9 (Table 3), and they may reduce the efficacy of CYP2C9 substrates. (pharmacytimes.com)

That meant there was a certain amount of variability to our substrate, which is something we have known for a while to be pretty prevalent in marine polysaccharides. (springernature.com)

The approach was to relate in vitro induction data ( E max and EC 50 values) with efficacious free plasma concentrations to calculate a relative induction score. (aspetjournals.org)

Thus, these enzymes and systems are often implicated in drug-drug interactions because of their effect on a drug's pharmacokinetics (e.g., drug exposure). (fda.gov)
Furthermore, by jointly analyzing the substrates (histone mutants) and enzymes (chromatin modifier deletions) we identify specific interactions between histone modifications and their regulators. (harvard.edu)

Subsequent studies were conducted to determine the relationship between in vitro induction data and in vivo induction response. (aspetjournals.org)
assays for evaluating induction are less well characterized and the relationships between in vitro and in vivo data less clear. (aspetjournals.org)
The rs66698963 polymorphism, a 22 bp insertion-deletion within FADS2 , is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro . (biorxiv.org)
In addition, DDL-701 partially restored interferon-β induction - an element of the host immune response - in an in vitro model system. (biorxiv.org)

substrate modification, through the cooperation of the E2 and E3 protein ligases. (wikipedia.org)
Induction of protein sumoylation by cellular stresses, J. Biol. (wikipedia.org)
Protein engineering efforts have all been done in E. coli , despite the complications imposed by the need for the release of intracellularly produced enzyme variants. (biomedcentral.com)
In this work, we have revealed that early viral protein UBCv1, the only known conjugating enzyme encoded by a virus, modulates innate immune and inflammatory signaling. (mdpi.com)
After isopropyl-1-thio-d-galactopyranoside (100 m) induction at 22 C for 24 h, protein were extracted having a buffer comprising 20 mm Tris-HCl, pH 7.5, 50 mm NaCl, 0.1% Triton X-100, 1 mm phenylmethylsulfonyl fluoride, and 0.5 mg/ml lysozyme. (healthanddietblog.info)
Botulinum neurotoxins (BoNTs) are a family of protein toxins consisting of seven known serotypes (BoNT/A-BoNT/G) and multiple subtypes within the serotypes, and all of which cause the disease botulism-a disease of great public health concern. (cdc.gov)

Identification of a substrate recognition site on Ubc9. (wikipedia.org)
Interestingly, CYP3A79 also shares five of six substrate recognition sites (SRS) with the SRS of other fish CYP3As, suggesting an evolutionary conservation of the function of these enzymes. (unipi.it)

The level of cell polarization in cells grown on transwell permeable supports was characterized at multiple timepoints with four different methods: transepithelial electrical resistance (TEER) measurement, lucifer yellow permeability assay, alkaline phosphatase expression and ZO-1 expression. (helsinki.fi)
Solid-state fermentation holds much potential compared with submerged fermentation methods for the utilization of agro-based wastes for enzyme production. (mdpi.com)

We therefore have systematically investigated the effects of 83 histone mutants, and 119 gene deletion mutants, on induction/repression dynamics of 170 transcripts in response to diamide stress in yeast. (harvard.edu)
THI5 is present within the yeast genome in multiple copies located on chromosomes VI (THI5), X (THI11) and XIV (THI12). (le.ac.uk)
Likely mechanisms by which the multiple copies of this gene have arisen and subsequent conclusions about the evolution of the yeast genome are discussed. (le.ac.uk)

Importantly, we find that chromatin regulators play far more pronounced roles during gene induction/repression than they do in steady-state expression. (harvard.edu)
Extensive work has been done on the catalytic behavior and mechanisms of these enzymes under steady-state conditions [ 5 - 7 ] and on the relationships between structure, dynamics, and catalytic activity [ 8 , 9 ]. (msu.ru)

For example, we knew from previous studies that the hemicellulose β-mannan was present during microalgae blooms, and also that the putative capability to degrade such substrates existed in some of our isolated bacteria. (springernature.com)

A total of 376 CAZymes including plentiful lignocellulolytic enzymes were predicted in P. parvum based on the fungal genomic sequence (25.8 Mb). (biomedcentral.com)

Induction of autophagy in the latter pathway is dependent on the interaction of Bcl-2 and Beclin 1. (helsinki.fi)

Commercial kits were used to measure the levels of serum myocardial enzymes and inflammatory factors. (spandidos-publications.com)
Apparent histologic injury and elevated levels of serum myocardial enzymes and inflammatory factors were observed in the myocardial I/R model. (spandidos-publications.com)

The initial catabolic pathway by I. sakaiensis involves two novel enzymes. (biomedcentral.com)
The formal reaction pathway depends on both the chemical structure of the substrate and the type of enzyme. (msu.ru)

For the other drugs in Table 1 (where other enzymes may be more important), the outcome of the interaction is more difficult to predict. (pharmacytimes.com)

Autoinduction of microsomal enzyme results in a shorter carbamazepine half-life (10-20 h) in patients who use the drug long-term compared with those with a short-term exposure (31-35 h). (medscape.com)

These include enzyme secretion, cellular adhesion, host defence evasion, and biofilm formation [ 7 ]. (encyclopedia.pub)

Eighteen compounds had been shown to be positive for induction, and six compounds had been shown to be negative for induction. (aspetjournals.org)

Diabetic cardiomyopathy is defined as a ventricular dysfunction initiated by alterations in cardiac energy substrates in the absence of coronary artery disease and hypertension. (hindawi.com)

Many authorities believe that if transaminase levels exceed two times the upper normal limit, a physician should consider alternative drug therapy or frequent monitoring of enzyme levels. (spiritsong.org)

The enzyme CYP2C19 is found primarily in the liver, as are the previous enzymes we discussed (CYP1A2 and CYP2C9). (pharmacytimes.com)

To date, various mechanisms have been suggested to explain the powerful tumor-suppressive effect of p53, including the induction of cell cycle arrest, senescence, and apoptosis. (nature.com)

This investigation disclosed the CAZyme repertoire of P. parvum at the genomic and proteomic levels, and elaborated on the promising potential of fungal lignocellulolytic enzymes upon saccharification of corn bran biomass after AHP pretreatment. (biomedcentral.com)

The most promising candidates are classified as cutinases (EC 3.1.1.74), but the turnover rates are only low to moderate, reflecting that PET is an unnatural substrate for these enzymes [ 5 ]. (biomedcentral.com)

DCM entails the damage of the myocardium through fibrosis, steatosis, apoptosis, and hypertrophy [ 3 ] and results from the switch of substrate supply to free fatty acids (FFA) that follows the reduced levels of insulin, glucose transporters, and glucose consumption [ 4 , 5 ]. (hindawi.com)
PGC‑1α, Nrf2, endothelial nitric oxide synthase and superoxide dismutase levels were significantly decreased, while inducible nitric oxide synthase and malondialdehyde levels were significantly increased by I/R induction. (spandidos-publications.com)

However, the authors did not provide results of their peptide substrate on multiple subtypes of BoNT. (cdc.gov)

We show that PETases can be functionally displayed on the bacterial cell surface, enabling screening of enzyme activity on PET microparticles - both while anchored to the cell and following solubilization of the enzymes. (biomedcentral.com)
their products enable the cell to utilise alternative hexoses as growth substrates. (le.ac.uk)

Drugs metabolized by CYP2C19 are called CYP2C19 substrates and are listed in Table 1. (pharmacytimes.com)
Relevant of mutagenicity and clastogenici- angiosarcomas of the liver, which carcinogens discussed in this chap- ty, including the induction of sister are rare tumours, were identified in ter do not include pharmaceutical chromatid exchange (SCE), chro- humans, rats, and mice exposed to drugs classified in Group 1, which mosomal aberrations (CA), and mi- vinyl chloride. (who.int)

The crystallinity and the limited accessibility to the ester linkages make PET unsusceptible to enzymatic hydrolysis, but a number of ester-cleaving enzymes have been reported active on the polyester [ 1 ]. (biomedcentral.com)

Even though HM site of AKT (Ser473) is a superb substrate for mTORC2 kinase, basic study of HM phosphorylation from the full-length AKT might not enable us to measure the aftereffect of PtdIns(3,4,5)P3 on mTORC2 kinase activity. (healthanddietblog.info)

Due to one of the ways bacteroidetes ensure they are the best polysaccharide degraders out there, they themselves are actually quite helpful in telling you what substrate exactly to search for. (springernature.com)

The etiology of atherosclerosis is unknown, but there are multiple factors that contribute to atherosclerotic plaque progression. (medscape.com)

Anatomy12

Organisms11

Diseases1

Chemicals and Drugs79

Analytical, Diagnostic and Therapeutic Techniques and Equipment23

Phenomena and Processes52

Information Science3

Health Care1

Inhibitors10

Pathways6

Cytochrome6

Arachidonic acid2

Inducers1

Ligands1

Biosynthesis2

CYP3A48

Carbohydrate-active2

Signaling molecules1

CYP4502

Homologous2

Enzymatic activity1

Inhibitor1

Inhibition2

Pharmacokinetic1

Metabolic1

Functional1

Degradation1

Clinically2

Proteins4

Genes5

Detect3

Metabolism3

Transporter3

Efficacy1

Variability1

Concentrations1

Interactions2

Vitro4

Protein6

Recognition2

Methods2

Yeast3

Steady-state2

Capability1

CAZymes1

Autophagy1

Inflammatory2

Pathway2

Interaction1

Exposure1

Cellular1

Compounds1

Dysfunction1

Drug1

Primarily1

Mechanisms1

Corn1

Moderate1

Levels2

Results1

Cell2

Drugs2

Active1

Activity1

Search1

Factors1