Abstract:
:This review focuses primarily on the mammalian medium and long-chain fatty acid coenzyme A ligases that have been implicated in the metabolism of xenobiotic carboxylic acids such as pesticides, arylpropionate non steroidal anti-inflammatory drugs and the hypolipidaemic clofibrate and its congeners. Evidence of multiplicity of mitochondrial and microsomal enzymes and their respective substrate/inhibitor profiles are discussed. For completeness, where appropriate, details of non-substrate inhibitors have also been included. Although knowledge is limited at present with respect to the medium-chain enzymes, aspects of regulation particularly the in vivo, in vitro role of peroxisome proliferators and current knowledge of the molecular biology of the long-chain fatty acid CoA ligase superfamily are documented. Additionally, alignment of thirteen cloned mammalian fatty acid CoA ligases using criteria established for the CYP and UGT superfamilies has enabled construction of a phylogenetic tree that clearly defines three families. Catalytic data are still limited and the xenobiotic substrate/inhibitor profiles of the recombinant proteins are incomplete. Finally, with increasing recognition of the importance of fatty acyl-CoA esters as physiological regulators of cell function including gene expression, the review concludes with a discussion of the metabolic fate and toxicity of xenobiotic acyl-CoA esters.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Knights KM,Drogemuller CJdoi
10.2174/1389200003339261keywords:
subject
Has Abstractpub_date
2000-07-01 00:00:00pages
49-66issue
1eissn
1389-2002issn
1875-5453journal_volume
1pub_type
杂志文章,评审abstract::Diabetes is associated with an increase risk for cardiovascular disease (CVD). Recently, macrovascular complications of diabetes have been shown to start before the development of diabetes. Indeed, several clinical studies have confirmed the increased risk of CVD in patients with impaired glucose tolerance (IGT). Sinc...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920009787522133
更新日期:2009-02-01 00:00:00
abstract::P-glycoprotein (P-gp) is involved in MDR and in neurodegenerative disorders such as Parkinson disease (PD), Alzheimer disease (AD) and epilepsy. Cytochrome P450 enzymes (CYP450s) catalyze the metabolism of a wide variety of endogenous and exogenous compounds including xenobiotics, drugs, environmental toxins, steroids...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920011798357015
更新日期:2011-10-01 00:00:00
abstract:BACKGROUND:Wound healing is a composite and vital process in which devitalized tissue layers and cellular structures repair themselves. Bronchiolitis is generally prompted by respiratory syncytial virus or human metapneumovirus; this condition is an acute inflammatory injury of bronchioles. Heart problems that develop ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666151210124713
更新日期:2016-01-01 00:00:00
abstract::The occurrence of idiosyncratic adverse drug reactions during late clinical trials or after a drug has been released can lead to a severe restriction in its use and even in its withdrawal. Metabolic activation of relatively inert functional groups to reactive electrophilic intermediates is considered to be an obligato...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200054021799
更新日期:2005-06-01 00:00:00
abstract:BACKGROUND:It is well known that ethanol can cause significant morbidity and mortality, and much of the related toxic effects can be explained by its metabolic profile. OBJECTIVE:This work performs a complete review of the metabolism of ethanol focusing on both major and minor metabolites. METHOD:An exhaustive litera...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200217666160125113806
更新日期:2016-01-01 00:00:00
abstract:BACKGROUND:Kidney dysfunction resulting from various drugs is an important issue during the drug development process. Traditional in vivo animal experiments are limited with respect to evaluating drug efficacy and nephrotoxicity due to discrepancies in drug pharmacokinetics and pharmacodynamics between humans and anima...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180309101844
更新日期:2018-01-01 00:00:00
abstract::The pressing need for targeting, detecting, monitoring, and treating diseased cells concomitantly gives rise to multi-functional nanomedicines, especially those that can combine diagnostic and therapeutic abilities, which are referred to as nanotheranostics. Recently, nanotheranostics are of significant clinical inter...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200211314060003
更新日期:2013-07-01 00:00:00
abstract::Transporters for organic anions and organic cations in kidney, liver, intestine, brain, and placenta play essential roles in drug disposition. The cloning and characterization of these transporters have significantly advanced our understanding of the molecular and cellular mechanisms of the drug disposition process. T...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200043489207
更新日期:2004-02-01 00:00:00
abstract:BACKGROUND:Neuropsychiatric diseases primarily characterized by dementia stand third in the global list of diseases causing disability. The poor water solubility, erratic oral absorption, low bioavailability, poor intestinal absorption, and the impeding action of the blood-brain barrier (BBB) are the major factors limi...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1573399816666200627214129
更新日期:2020-01-01 00:00:00
abstract::Vasopressin (AVP) and its receptors play a pivotal role in maintaining body homeostasis under physiological and pathophysiological conditions. As a consequence, the vasopressin system has emerged as an important target for both diagnostic and therapeutic applications in a number of medical conditions. Stoichiometric g...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200218666170119145900
更新日期:2017-01-01 00:00:00
abstract::Metabolism of xenobiotics is often seen as an exclusive function of the liver, but some current findings support the notion that the lungs, kidneys and intestine may contribute considerably. After the establishment of the use of liver slices as a useful in vitro model to study metabolism and toxicity of xenobiotics, t...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200023338071
更新日期:2002-02-01 00:00:00
abstract::We present a review of recent investigations of anticancer drug bexarotene in this article. As one of the novel synthetic analogs of retinoids, bexarotene selectively binds to and activates the retinoid X receptor (RXRs) subfamilies, exerting a prophylactic and therapeutic effect on a large series of tumors in vitro a...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920021702160114121706
更新日期:2016-01-01 00:00:00
abstract::Decarboxylation, reduction and hydrolysis can yield active metabolites from the parent drug. Major therapeutic indications and metabolic routes of these drugs are reviewed. Changes in the logP values (determined and calculated) from the parent drug to the active metabolite show certain characteristics in comparison to...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012800840437
更新日期:2012-07-01 00:00:00
abstract::Knowledge regarding cytochrome P450 (P450) is crucial to the fields of drug therapy and drug development, as well as in our understanding of the mechanisms underlying the metabolic activation of potentially toxic and carcinogenic compounds. Escherichia coli is the most extensively utilized host in the production of re...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920006776873472
更新日期:2006-05-01 00:00:00
abstract:BACKGROUND:Nanoparticles (NPs) are being used extensively owing to their increased surface area, targeted delivery and enhanced retention. NPs have the potential to be used in many disease conditions. Despite widespread use, their toxicity and clinical safety still remain a major concern. OBJECTIVE:The purpose of this...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200221666200103091753
更新日期:2019-01-01 00:00:00
abstract::When used at a high dose, many anticancer drugs produce undesirable side effects including hepatotoxicity. Transdermal delivery bypasses first-pass metabolism, allowing the use of a lower dose of drug while decreasing systemic toxicity. In this review, we summarize various advanced technologies for improving anticance...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008785821693
更新日期:2008-09-01 00:00:00
abstract::Recent advances in the biological and analytical sciences have led to unprecedented interest in the discovery and quantitation of endogenous molecules that serve as indicators of drug safety, mechanism of action, efficacy, and disease state progression. By allowing for improved decision-making, these indicators, refer...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920006777697918
更新日期:2006-06-01 00:00:00
abstract::Cytochrome P450s (P450 or CYPs) comprise a superfamily of enzymes that catalyze the oxidation of a wide variety of xenobiotic chemicals. Although most of P450 inhibitors decrease the metabolic activities mediated by the corresponding P450 forms, unexpected phenomena, which are called as activation or heterotropic coop...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008784746364
更新日期:2008-06-01 00:00:00
abstract:BACKGROUND:The prolonged circulation time of nanoparticles in the blood is a prerequisite to realize a controlled and targeted (passive or active targeting) release of the encapsulated gene/drug at the desired site of action. The most popular method to mask or camouflage nanoparticles is the adsorbed, grafted or conjug...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666171207120643
更新日期:2018-01-01 00:00:00
abstract:BACKGROUND:Bioequivalence studies are a vital part of drug development. The average bioequivalence approach is the standard method of assessment to conclude whether the generic product is bioequivalent to the innovator product. Of late, debates are on whether the average bioequivalence approach adequately addresses dru...
journal_title:Current drug metabolism
pub_type: 杂志文章,随机对照试验
doi:10.2174/1389200221666200401105119
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:In the last few years, the use of modified Carbon Nanomaterials (CNMs) for theranostics (therapeutic and diagnosis) applications is a new and rapidly growing area in pharmacy and medical fields. Owing to this, their specific physicochemical behaviors like high stability, drug loading, surface area to volume ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180925094515
更新日期:2019-01-01 00:00:00
abstract::5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT) belongs to a group of naturally-occurring psychoactive indolealkylamine drugs. It acts as a nonselective serotonin (5-HT) agonist and causes many physiological and behavioral changes. 5-MeO-DMT is O-demethylated by polymorphic cytochrome P450 2D6 (CYP2D6) to an active metab...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920010794233495
更新日期:2010-10-01 00:00:00
abstract::Early understanding of the metabolic pathway and potential interaction of new drug candidates with other drugs is one of the goals of preclinical studies in the drug discovery process. Although other body organs are involved in drug biotransformation, the liver is the predominant organ of metabolism for a wide range o...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012798918426
更新日期:2012-02-01 00:00:00
abstract::To understand the sophisticated dynamic behaviors of drug elution and permeation in the gastrointestinal tract (GIT), researchers have tried to reemerge it by employing various in vitro experimental models. However, official in vitro apparatuses routinely used for quality control purposes, employ simple, non-physiolog...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200216666150812123836
更新日期:2015-01-01 00:00:00
abstract::Brain, the centre of the nervous system and an integral part the body, is protected by two anatomical and physiological barriers- Blood-Brain Barrier (BBB) and Blood-Cerebrospinal Fluid Barrier (BCSFB). Blood-Brain Barrier is a very complex and highly organized multicellular structure that shields the brain from harmf...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200218666170113125132
更新日期:2017-01-01 00:00:00
abstract::Bioavailability of orally administered drugs can be influenced by a number of factors including release from the formulation, dissolution, stability in the gastrointestinal (GI) environment, permeability through the gut wall and first-pass gut wall and hepatic metabolism. Although there are various enzymes in the gut ...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920010794328913
更新日期:2010-11-01 00:00:00
abstract::With the recent advancement in nanoscience and nanotechnology, there is a growing demand for assessment of the toxicological effects of nano materials to humans and other biological systems. And a predictive toxicology approach that uses in vitro screening assays in conjunction with in vivo study results are widely em...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200216666151015113720
更新日期:2015-01-01 00:00:00
abstract::This paper reviews the metabolism of new designer drugs of abuse that have emerged on the black market during the last years and is an update of a review published in 2005. The presented review contains data concerning the so-called 2C compounds (phenethylamine type) such as 4-bromo-2,5-dimethoxy-beta-phenethylamine (...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920010791526042
更新日期:2010-06-01 00:00:00
abstract::The possibility to treat central nervous system (CNS) disorders is strongly limited by the poor access of many therapeutic agent to the target tissues. This is mainly due to the presence of the blood-brain barrier (BBB), formed by a complex interplay of endothelial cells, astrocyte and pericytes, through which only se...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012798356943
更新日期:2012-01-01 00:00:00
abstract::The transcription factor networks that regulate basal and xenobiotic-modulated expression of the hepatic sulfotransferases affect the dynamics of xenobiotic detoxication, carcinogen bioactivation and metabolic homeostasis. Emerging evidence suggests that liver-enriched transcription factors, the aryl hydrocarbon (Ah) ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200054633871
更新日期:2005-08-01 00:00:00