Microsomal enzymesAlpha-1,4-glucosidaseCYP2C9CYP3A4 and CYP2D6RecombinantCytosolMetabolismHepatocytesHumansHepatic enzymesBiosynthesisCYP2D6ProteinNADPHInhibitionSubstratesHumanRatsInhibitorYieldsHepatocyteSubstrateActivitySynthesisHemeConcentrationDeficiencyDextromethorphanExposureToxicityDrugWidelyActiveMouseCellGroups
Microsomal enzymes3
- Not the microsomes are induced, but microsomal enzymes or cytochrome(s) P-450. (cdc.gov)
- These results suggest that yeast cells, cheap and easy to grow, could provide an ideal environment for bulk production of highly active human CYP microsomal enzymes so that they could be used more widely than they are now. (oreilly.com)
- Since 1994 there has been a rapid expansion of information about the specificity of hepatic microsomal enzymes of the cytochrome P450 family for the metabolism of different drugs. (liposuction.com)
Alpha-1,4-glucosidase1
- Its clinical presentation clearly differs from other forms of GSD, because it is caused by the deficiency of the lysosomal enzyme, alpha-1,4-glucosidase, leading to the pathologic accumulation of normally structured glycogen within the lysosomes of most tissues, differs Three forms of the disease exist: infantile-onset, late-onset juvenile and adult onset. (medscape.com)
CYP2C98
- Although most studies have implicated CYP2C9 as the exclusive catalyst of hepatic tolbutamide hydroxylation in humans, there is evidence that other CYP2C enzymes (e.g. (aspetjournals.org)
- Western blotting revealed that the absorbed anti-human CYP2C9 preparation reacted with only recombinant CYP2C9 and the corresponding native protein in hepatic microsomes, and no longer recognized CYP2C19 and CYP2C8. (aspetjournals.org)
- Monospecific anti-CYP2C9 was also found to inhibit rates of tolbutamide hydroxylation by 93 ± 4 and 78 ± 6% in CYP2C19-deficient and CYP2C19-containing human liver microsomes, respectively. (aspetjournals.org)
- Taken together, our results indicate that both CYP2C9 and CYP2C19 are involved in tolbutamide hydroxylation by human liver microsomes, and that CYP2C19 underlies at least 14 to 22% of tolbutamide metabolism. (aspetjournals.org)
- Although expression of CYP2C19 in human liver is less than that of CYP2C9, it may play an important role in tolbutamide disposition in subjects expressing either high levels of CYP2C19 or a catalytically deficient CYP2C9 enzyme. (aspetjournals.org)
- similar to that of CYP2C9, thereby obviating kinetic approaches for determining the contribution of the former enzyme to this microsomal drug-metabolizing reaction. (aspetjournals.org)
- In the individual microsomes, CYP2C9 showed the highest protein expression level, and CYP1A2, 2A6, 2C19, and 3A4 protein expression exhibited more than a 20-fold difference among individuals. (nih.gov)
- Myricetin inhibited the liver metabolizing enzymes CYP3A4 and CYP2C9 [ 12 ]. (hindawi.com)
CYP3A4 and CYP2D62
- The metabolic activities of enzymes CYP3A4 and CYP2D6 were assessed. (hindawi.com)
- The newer antidepressant selective serotonin reuptake inhibitors (SSRI) such as sertraline are metabolized by the hepatic enzymes CYP3A4 and CYP2D6. (liposuction.com)
Recombinant2
- In particular, the availability of substrate and inhibitor "probes" for the major hepatic drug metabolizing UGTs together with batteries of recombinant enzymes allow the reaction phenotyping of drug glucuronidation reactions. (nih.gov)
- In vitro glucuronidation kinetics of deoxynivalenol by human and animal microsomes and recombinant human UGT enzymes. (boku.ac.at)
Cytosol2
- GSD type Ic is deficiency of translocase T2 that carries inorganic phosphates from microsomes into the cytosol and pyrophosphates from the cytosol into microsomes. (medscape.com)
- GSD type Id is deficiency in a transporter that translocates free glucose molecules from microsomes into the cytosol. (medscape.com)
Metabolism6
- This enzyme participates in glycerolipid metabolism. (wikipedia.org)
- Human CYP450 enzymes, naturally bound to livers' endoplasmic reticular (ER) membranes, are used for drug-metabolism studies and commercially produced from genetically engineered insect/bacterial cells. (oreilly.com)
- The specific cytochrome P450 enzyme responsible for the metabolism of flurazepam has not been identified. (liposuction.com)
- A carbon radical is formed during the oxidative metabolism of phenelzine that reacts with the prosthetic heme group of cytochrome P 450 and irreversibly inactivates the enzyme. (usp.br)
- Parathion metabolism was efficient in PB-microsomes (Km values for 4-nitrophenol and paraoxon formation were 13 microM and 10 microM, respectively) and in the reconstituted system (corresponding Km values were 19 microM and 14 microM). (aspetjournals.org)
- Compounds potentially used with MDMA [fluoxetine, paroxetine, (-)-cocaine] demonstrated significant inhibition of MDMA metabolism in both human liver and CYP2D6.1-expressing microsomes. (mdma.net)
Hepatocytes1
- Catabolism of 3'-azido-3'-deoxythymidine in hepatocytes and liver microsomes, with evidence of formation of 3'-amino-3'-deoxythymidine, a highly toxic catabolite for human bone marrow cells. (aspetjournals.org)
Humans2
- Major advances in the characterization of uridine diphosphate (UDP)-glucuronosyltransferase (UGT) enzyme substrate and inhibitor selectivities and the development of experimental paradigms to investigate xenobiotic glucuronidation in vitro now permit the prediction of a range of drug-glucuronidation parameters in humans. (nih.gov)
- IDI2 determines isoprene production as only DMAPP sources isoprene and unlike plants, humans lack isoprene synthase and its enzyme homologue. (nature.com)
Hepatic enzymes1
- We hypothesize that hepatic enzymes are capable of escalating lung epithelial cell damage caused by EB, ST, and NA. (cdc.gov)
Biosynthesis1
- Methyl transferring enzyme system of microsomes in the biosynthesis of lecithin (phosphatidylcholine). (microbiologyresearch.org)
CYP2D63
- The powder and alcoholic extract of dried seeds of garden cress were investigated for their effect on metabolic activity of CYP2D6 and CYP3A4 enzymes. (hindawi.com)
- Dextromethorphan was used as a common marker for measuring metabolic activity of CYP2D6 and CYP3A4 enzymes. (hindawi.com)
- We investigated the demethylenation of MDMA and dextromethorphan (DEX), as a comparison drug, in reconstituted microsomes expressing the variant CYP2D6 alleles (*)2, (*)10, and (*)17, all of which have been linked to decreased enzyme activity. (mdma.net)
Protein4
- The absolute protein expression levels of 11 CYP isoforms were determined from one pooled and 10 individual human liver microsomes. (nih.gov)
- Therapeutic proteins (e.g., antibodies, vaccines, enzymes, cytokines, and growth factors) account for almost half of this market, followed by industrial proteins (e.g., technical enzymes) and research reagents (e.g., antibodies for protein detection and purification) ( Markets and Markets, 2017 ). (frontiersin.org)
- Liver microsomes from four rats of each sex per group were assayed for protein and cytochrome P450 content, and the activities of UDP-glucuronyltransferase and several monooxygenases were determined (Vermeir, 1996). (inchem.org)
- Excessive Ca 2 + entry through glutamate receptors activates a large array of potential neurotoxic mechanisms, which include activation of enzymes such as phospholipases, calpains and other proteases, protein kinases, nitric oxide synthetase, endonucleases, as well as reactive oxygen species (for review, see Sattler and Tymianski, 2000 ). (jneurosci.org)
NADPH3
- In in vitro studies, microsomes were incubated with NADPH in presence and absence of different concentrations of seeds extract. (hindawi.com)
- 5 microM) with NADPH-supplemented microsomes from PB-pretreated rat liver decreased holo-P450, heme loss was not observed near the Ki values. (aspetjournals.org)
- Studies using rat and human liver microsomes demonstrated that the rate of formation of AMT and GAMT increased in the presence of NADPH, suggesting the involvement of a NADPH-dependent enzyme system. (aspetjournals.org)
Inhibition3
- IC 50 values for Sacchrosome inhibition by known CYP inhibitors are similar to those published using human-liver-microsomes (HLMs). (oreilly.com)
- In-vitro metabolic inhibition studies using rat and human liver microsomes and intestinal absorption studies of riluzole in a rat everted gut-sac model were conducted to elucidate the mechanism of interaction. (researchgate.net)
- Mechanistically, the expression of 3ß-hydroxysteroid dehydrogenase/isomerase, the rate-limiting enzyme in cortisol synthesis, was increased with autophagy inhibition mediated by orexin-A/OX1R. (bvsalud.org)
Substrates3
- Prolyl oligopeptidase (PREP) is a peptidase enzyme that has several substrates. (helsinki.fi)
- The metabolic enzyme modulation also leads to incidences of altered bioavailability and pharmacokinetics of therapeutic substrates. (hindawi.com)
- When two or three drugs are each substrates for the same enzyme, there is a possibility for an adverse drug reaction when used simultaneously. (liposuction.com)
Human6
- Tolbutamide is a sulfonylurea-type oral hypoglycemic agent whose action is terminated by hydroxylation of the tolylsulfonyl methyl moiety catalyzed by cytochrome P-450 (CYP) enzymes of the human CYP2C subfamily. (aspetjournals.org)
- In vitro and clinical studies were conducted on human liver microsomes and healthy human subjects, respectively. (hindawi.com)
- The human liver microsomes were employed for in vitro investigation, while in vivo study was conducted on healthy human subjects. (hindawi.com)
- Here we show that six major human liver CYP enzymes (1A2/2C9/2C19/2D6/2E1/3A4), isolated from baker's yeast as ER-bound microsomes (Sacchrosomes™) in yields of 120-325 nmol/L, are 0.5-25 fold more active than commercial enzymes. (oreilly.com)
- While the human liver microsomal system demonstrated rapid clearance by CYP enzymes, the hepatocyte incubations showed much slower clearance, possibly providing some insight into the long duration of carfentanils effects. (diva-portal.org)
- Involvement of cytochrome P 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. (or.jp)
Rats2
- Further studies of the induction of the liver microsomal drug-hydroxylating enzyme system by pretreatment of rats with various drugs are presented. (rupress.org)
- At low concentration, parathion was a competitive inhibitor of 2B1-mediated androstenedione 16 beta-hydroxylation (Ki = 0.44 +/- 0.07 microM) and of 7-pentylresorufin O-depentylation (Ki = 0.40 +/- 0.03 microM) in microsomes from PB-pretreated rats and was similarly effective against androstenedione 16 alpha- and 16 beta-hydroxylation catalyzed by purified 2B1. (aspetjournals.org)
Inhibitor1
- Cobicistat is a mechanism-based inhibitor of cytochrome P450 (CYP) enzymes of the CYP3A family. (rxlist.com)
Yields1
- The transformation of phenelzine by rat liver microsomes yields 2-phenylacetaldehyde, 2-phenylethanol and ethyl-benzene. (usp.br)
Hepatocyte1
- thus, these enzymes are sensitive indicators of hepatocyte injury. (msdmanuals.com)
Substrate1
- 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)
Activity1
- In contrast, the previously described inactivation process occurred only at considerably higher parathion concentrations, at which concentrations enzyme activity was already extensively inhibited. (aspetjournals.org)
Synthesis1
- The drug-induced enzyme synthesis is unaffected by adrenalectomy. (rupress.org)
Heme1
- Heme oxygenase, an essential enzyme in heme catabolism, cleaves heme to form biliverdin, which is subsequently converted to bilirubin by biliverdin reductase, and carbon monoxide, a putative neurotransmitter. (genetex.com)
Concentration1
- The early increase in these enzymes is found in the microsomal subfraction consisting of rough-surfaced vesicles, whereas repeated administration of the inducing drug results in a concentration of the enzymes in the smooth-surfaced vesicles. (rupress.org)
Deficiency3
- It is an autosomal recessive disorder in which there is an AGL gene mutations which causes deficiency in glycogen debranchinging enzyme and limited storage of dextrin. (medscape.com)
- GSD type IV, also known as amylopectinosis, Glycogen Branching enzyme deficiency (GBE) or Andersen disease, is a rare disease that leads to early death. (medscape.com)
- Hepatic phosphorylase deficiency or deficiency of other enzymes that form a cascade necessary for liver phosphorylase activation cause the disease. (medscape.com)
Dextromethorphan1
- Dextromethorphan (DEX) was used as common marker for both enzymes. (hindawi.com)
Exposure1
- With the active microsomes present during exposure to 3 and 0.3mM of NA, a significant (20%) drop in HBE1 cell density was detected. (cdc.gov)
Toxicity2
- Liver microsome-generated EB metabolites are more potent than liver microsome-generated NA or ST metabolites in causing toxicity in the mouse trachea epithelial cells. (cdc.gov)
- However, in recent years, there are large numbers of reports related to herbal toxicity and herb's effects on basic activities such as modulation of drug metabolizing enzymes and drug transporters and interference with bioavailability and pharmacokinetics of concomitantly administered therapeutic substances [ 1 - 3 ]. (hindawi.com)
Drug1
- Consequently, we studied the potential for herb-drug interactions involving cytochrome P450 (P450), UDP-glucuronosyltransferase (UGT), and sulfotransferase (SULT) enzymes. (aspetjournals.org)
Widely1
- Proteins are also widely used in industry, including enzymes used to manufacture textiles and chemicals and to process food and feed. (frontiersin.org)
Active4
- MuEC exposed to ST or NA at 5microM and 10microM resulted in no significant cell death with or without active liver microsomes. (cdc.gov)
- For a higher dose of NA, 20microM, MuEC cell death was observed, but the extents were similar in the active and boiled microsome groups (approximately 50% decrease in cell density). (cdc.gov)
- No significant cell death was detected in HBE1 cells exposed to 5microM to 3mM NA without active liver microsomes present. (cdc.gov)
- 1%) IDI2 stop-gain mutation, which causes losses of enzyme active site and Mg 2+ -cofactor binding sites. (nature.com)
Mouse1
- Cells were exposed to 5microM or 10microM EB, 5microM or 10microM ST, or 5microM to 3mM NA, in media containing female mouse liver microsomes. (cdc.gov)
Cell2
- MuEC cells exposed to 10microM EB with liver microsomes present resulted in a 50% decrease in cell density. (cdc.gov)
- No significant MuEC cell death occurred with 10microM EB and boiled liver microsomes. (cdc.gov)
Groups1
- This enzyme belongs to the family of transferases, specifically those glycosyltransferases that do not transfer hexosyl or pentosyl groups. (wikipedia.org)