Abstract:
:The present review aims to give an overview of the cytochrome P450 8B (CYP8B) and cytochrome P450 4A (CYP4A) subfamilies in relation to biosynthesis of bile acids, in particular trihydroxy bile acids. Trihydroxy bile acids are basically required in most species and have an impact on cholesterol and lipid metabolism. The primary trihydroxy bile acid in most mammals is cholic acid. Some species produce other important trihydroxy bile acids, for example the adult pig which produce hyocholic acid instead of cholic acid. The position of the third hydroxyl group in cholic acid and hyocholic acid, 12alpha or 6alpha position, respectively, has a profound effect on the hydrophilic-hydrophobic property of the trihydroxy bile acids. The CYP8B subfamily is required for introduction of the 12alpha-hydroxyl group in cholic acid biosynthesis. The enzyme responsible for 6alpha-hydroxylation in hyocholic acid biosynthesis, however, varies among species. This review will discuss, in particular, porcine members of the CYP8B and CYP4A subfamilies because interesting findings regarding members of these subfamilies have recently been recognized in this species. CYP8B1 was for a long time believed to be absent in the pig but was recently found to be expressed in fetal pig liver. The enzyme catalyzing the 6alpha-hydroxylation in hyocholic acid biosynthesis in pig was found to be an atypical member of the CYP4A subfamily, denoted CYP4A21. The review presents bile acid biosynthesis in view of these findings and discusses physiochemical properties and developmental-dependent aspects related cholic acid and hyocholic acid biosynthesis.
journal_name
Curr Drug Metabjournal_title
Current drug metabolismauthors
Lundell K,Wikvall Kdoi
10.2174/138920008784220574subject
Has Abstractpub_date
2008-05-01 00:00:00pages
323-31issue
4eissn
1389-2002issn
1875-5453journal_volume
9pub_type
杂志文章,评审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
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::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::Accompanying with hot discussions on developing multi-target drugs for the therapy of multi-gene diseases, herbal medicines are receiving more and more attention worldwide in both academic and industrial fields. Pharmacokinetic and metabolic research is one of the important issues for intensive understanding of therap...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920012803341285
更新日期:2012-11-01 00:00:00
abstract::The binding of drugs with serum proteins can affect the activity, distribution, rate of excretion, and toxicity of pharmaceutical agents in the body. One tool that can be used to quickly analyze and characterize these interactions is high-performance affinity chromatography (HPAC). This review shows how HPAC can be us...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920011795202938
更新日期:2011-05-01 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::Toxicogenomics is defined as an integration of genomics (transcriptomics, proteomics and metabolomics) and toxicology. It is a scientific field that studies how the genome is involved in responses to environmental stressors and toxicants. It combines studies of mRNA expression, cell and tissue-wide protein expression ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920008783884696
更新日期:2008-03-01 00:00:00
abstract::L-Carnitine has important roles in intermediary metabolism and patients with end-stage renal disease who are undergoing hemodialysis may develop a secondary L-carnitine deficiency. The extent of accumulation of the metabolites trimethylamine and trimethylamine-N-oxide when L-carnitine is administered orally has not be...
journal_title:Current drug metabolism
pub_type: 临床试验,杂志文章
doi:10.2174/138920006778520561
更新日期:2006-10-01 00:00:00
abstract:BACKGROUND:Increasing incidences of type 2 diabetes make it necessary to have a better understanding of the risk factors for its prediction. Taking a note of resilience in risk factors, dynamics of the emerging factors other than traditional ones are showing a great interest in recent years which imprints a significant...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180628170431
更新日期:2018-01-01 00:00:00
abstract::Part I of this article published in the previous issue of Current Drug Metabolism discussed the substrate specificity, inhibitor selectivity and structure-activity relationship (SAR) of human CYP2C9. The features of CYP2C9 pharmacophore and SAR models have been elaborated. Part II of this article will address the homo...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920009790820101
更新日期:2009-12-01 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::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:BACKGROUND:Drug-metabolizing enzymes and transporters play key roles in drug disposition and drug interactions. The alterations of their expression will influence drug pharmacokinetics and pharmacodynamics. However, the changes in the expression of enzymes and transporters in the disease state are still unclear. OBJEC...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200512113731
更新日期:2020-01-01 00:00:00
abstract::Fluoropyrimidines and oxaliplatin continued to be the mainstay of therapeutic regimens in the treatment of colorectal cancer (CRC). For this reason, pharmacokinetic and metabolism of these drugs were analyzed and the identification of accurate and validated predictive, prognostic and toxicity markers became necessary ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920011798062300
更新日期:2011-12-01 00:00:00
abstract::Drug metabolite identification and metabolic characteristics analysis play a crucial role in new drug research and development, because they can lead to varied efficacy, severe adverse reactions, and even toxicity. Classical methodologies for metabolite identification have mainly been based on mass spectrometry (MS) c...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200216666141230105649
更新日期:2014-01-01 00:00:00
abstract::In recent years several arylpiperazine derivatives have reached the stage of clinical application, mainly for the treatment of depression, psychosis or anxiety. Examples are the pyrimidinylpiperazine buspirone, the chlorophenylpiperazine derivatives nefazodone and trazodone, the dichlorophenylpiperazine aripiprazole a...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920007781368908
更新日期:2007-08-01 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::Photodynamic therapy (PDT) combines photosensitizer, visible light and oxygen, which has the characteristics of high selectivity, minimal invasiveness, low side effect, and allowing repetitive application. The photophysics and mechanisms leading to cell death mediated by PDT have been studied extensively, and PDT has ...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/138920009790274559
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND:The red-crowned crane (Grus japonensis) is one of the most vulnerable bird species in the world. Mycotoxins are toxic secondary metabolites produced by fungi and considered naturally unavoidable contaminants in animal feed. Our recent survey indicated that the mycotoxins had the potential to contaminate redc...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200726221126
更新日期:2020-01-01 00:00:00
abstract:BACKGROUND:Drug-induced cholestasis is a risk factor in the progression of drug candidates, and poses a serious health hazard if not detected before going into a human. Intrahepatic accumulation of Bile Acids (BAs) represents a characteristic phenomenon associated with drug-induced cholestasis. METHODS:This review wil...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200219666180427165035
更新日期:2018-01-01 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::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::Ageing is characterized by a progressive decline in the functional reserve of multiple organs and systems, which can influence drug disposition. In addition, comorbidity and polypharmacy are highly prevalent in the elderly. As ageing is associated with some reduction in first-pass metabolism, bioavailability of a few ...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/138920011796504527
更新日期:2011-09-01 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::Talin is an intracellular cytoskeletal protein and one of the major components of the focal adhesion complex. It mainly acts as an interlink between transmembrane integrin receptors and cytosolic F-actin. Apart from integrins and actin, it also interacts with various other proteins in the adhesion complex to regulate ...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221666200214114018
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: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::Membrane transporters play an important role in intestinal absorption, distribution and clearance of drugs. Additionally transporters along with enzymes regulate tissue exposures (e.g. liver, kidney and brain), which are important for safety and efficacy considerations. Early identification of transporters involved gu...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200221999210101233340
更新日期:2021-01-01 00:00:00
abstract::The nature and level of systemic exposure to the active herbal constituents will profoundly affect their effects at action sites, which is fundamental in understanding their roles in the overall beneficial effects of a herbal medicine. The objective of this study is to gain a full picture of the systemic exposure to v...
journal_title:Current drug metabolism
pub_type: 杂志文章
doi:10.2174/1389200211209050494
更新日期:2012-06-01 00:00:00
abstract::Several epidemiological studies throughout the years have suggested that polyphenols from fruits and vegetables promote health and reduce the risk of certain chronic and neurodegenerative diseases. Yet, it has been proved to be extremely difficult to quantitatively establish the benefit afforded by polyphenols, princi...
journal_title:Current drug metabolism
pub_type: 杂志文章,评审
doi:10.2174/1389200214666131210144115
更新日期:2014-01-01 00:00:00