Abstract：
:The cytochrome P450 (P450) field came out of interest in the metabolism of drugs, carcinogens, and steroids, which remain major focal points. Over the years we have come to understand the P450 system components, the multiplicity of P450s, and many aspects of the regulation of the genes and also the catalytic mechanism. Many crystal structures are now becoming available. The significance of P450 in in vivo metabolism is appreciated, particularly in the context of pharmacogenetics. Current scientific issues involve posttranslational modification, gene regulation, component interactions, structures of P450 complexed with ligands, details of high-valent oxygen chemistry, the nature and influence of rate-limiting steps, greater details about some reaction steps, cooperativity, and the relevance of P450 variations to cancer risk. Some emerging research areas involve new methods of analysis of ligand interactions, roles of conformational changes linked to individual reaction steps, functions of orphan P450s, "molecular breeding" of new P450 functions and enhanced activity, and the utilization of P450s in chemical synthesis.
journal_name
Drug Metab Revjournal_title
Drug metabolism reviewsauthors
Guengerich FPdoi
10.1081/dmr-120033996keywords:
subject
Has Abstractpub_date
2004-05-01 00:00:00pages
159-97issue
2eissn
0360-2532issn
1097-9883journal_volume
36pub_type
杂志文章,评审abstract：:Glutathione S-transferase P1-1 (GSTP) is one member of the family of GSTs and is ubiquitously expressed in human tissues. The literature is replete with reports of high levels of GSTP linked either with cancer incidence or drug resistance, and yet no entirely cogent explanation for these correlations exists. The catal...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2011.552912
更新日期：2011-05-01 00:00:00
abstract：:Population pharmacokinetics describe the typical relationships between physiology (both normal and disease altered) and pharmacokinetics, the interindividual variability in these relationships, and their residual intraindividual variability. Knowledge of population kinetics can help one to choose initial drug dosage, ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章
doi：10.3109/03602538409015063
更新日期：1984-01-01 00:00:00
abstract：:S-carboxymethyl-L-cysteine, the side-chain carboxymethyl derivative of the sulfur-containing amino acid, cysteine, has been known and available for almost 80 years. During this time, it has been put to a variety of uses, but it is within the field of respiratory medicine that, presently, it has found a clinical niche....
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2011.631015
更新日期：2012-05-01 00:00:00
abstract：:At present, the methods and enzymology of the UDP-glucuronosyltransferases (UGTs) lag behind that of the cytochromes P450 (CYPs). About 15 human UGTs have been identified, and knowledge about their regulation, substrate selectivity, and tissue distribution has progressed recently. Alamethicin has been characterized as...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-120000653
更新日期：2001-08-01 00:00:00
abstract：:The cannabinoid receptor 1 (CB1) is a G protein-coupled receptor (GPCR) that is located primarily in the central nervous system. CB1 is a therapeutic target which may impact pathways to mediate pain, neurodegenerative disorders, hunger, and drug-seeking behavior. Despite these benefits, development of orthosteric ther...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2018.1428342
更新日期：2018-02-01 00:00:00
abstract：:The lung, which is in intimate contact with the external environment, is exposed to a number of toxicants both by virtue of its large surface area and because it receives 100% of the cardiac output. Lung diseases are a major disease entity in the U.S. population ranking third in terms of morbidity and mortality. Despi...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-120015694
更新日期：2002-11-01 00:00:00
abstract：:Cyclindole was extensively metabolized and eliminated primarily via the kidneys from most laboratory animals and man. Only in the dog was cyclindole a major urinary component. Cyclindole was metabolized by N-demethylation and/or hydroxylation. In studies utilizing radiolabeled drug, the primary urinary component was p...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602538008994027
更新日期：1980-01-01 00:00:00
abstract：:The multiple functions of NAD(P)H:quinone oxidoreductase 1 (NQO1, DT-diaphorase) in the cell are reviewed. NQO1 has long been viewed as a chemoprotective enzyme involved in cellular defense against the electrophilic and oxidizing metabolites of xenobiotic quinones. It also participates in reduction of endogenous quino...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-200033465
更新日期：2004-10-01 00:00:00
abstract：:Aryl and heterocyclic amines are of particular interest because of their carcinogenicity. The N-hydroxy derivatives are formed by oxidation, usually by the cytochrome P450 (P450) enzymes and most often by P450 family 1. The mechanism of oxidation appears to resemble that of other P450 reactions. The N-hydroxy products...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-120005663
更新日期：2002-08-01 00:00:00
abstract：:An association between marijuana use and schizophrenia has been noted for decades, and the recent emergence of high-efficacy synthetic cannabinoids (SCBs) as drugs of abuse has lead to a growing number of clinical reports of persistent psychotic effects in users of these substances. The mechanisms underlying SCB-elici...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2018.1428343
更新日期：2018-02-01 00:00:00
abstract：:Much is known about the distal DNA damage repair response. In particular, many of the enzymes and auxiliary proteins that participate in DNA repair have been characterized. In addition, knowledge of signaling pathways activated in response to DNA damage is increasing. In contrast, comparatively less is known of DNA da...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530600959649
更新日期：2006-01-01 00:00:00
abstract：:This article reviews the regulatory, social, policy, and other issues that will shape the development of pharmacogenomics applications. We identify and analyze 19 key public policy issues, ranging from the economic incentives for linked diagnostic-drug development, to the regulation of tests and drugs, and to privacy ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530801952500
更新日期：2008-01-01 00:00:00
abstract：:The mitochondrial amidoxime-reducing component (mARC) is a recently discovered molybdenum-containing enzyme in mammalians. Upon reconstitution with the electron transport proteins, cytochrome b(5) and its reductase, this molybdenum enzyme is capable of reducing N-hydroxylated compounds. It was named mARC because the N...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2011.608682
更新日期：2011-11-01 00:00:00
abstract：:Indirect evidence for the participation of cytochrome P450 (P450) in the microsomal N-oxygenation of primary and N-substituted amine functions is presented by studies employing diagnostic modifiers of the hemoprotein system as well as immunochemical approaches. Experiments with recombinant hemoproteins or isozymes pur...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-120005646
更新日期：2002-08-01 00:00:00
abstract：:The rat P450IIA subfamily was characterized at the protein, cDNA, and gene level. The purified IIA1 and IIA2 P-450s displayed distinct positional specificities toward hydroxylation of the prototype substrate testosterone. The IIA1 and IIA2 genes were also regulated differently during development; IIA1 was expressed wi...
journal_title：Drug metabolism reviews
pub_type： 杂志文章
doi：10.3109/03602538909103582
更新日期：1989-01-01 00:00:00
abstract：:Human tumors arise from multiple genetic changes that gradually transform growth-limited cells into highly invasive cells that are unresponsive to growth controls. The genetic evolution of normal cells into cancer cells is largely determined by the fidelity of DNA replication, repair, and division. Cell-cycle arrest i...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-100102335
更新日期：2000-08-01 00:00:00
abstract：:Voriconazole, a second-generation triazole frequently used for the prophylaxis and treatment of invasive fungal infections, undergoes complex metabolism mainly involving various (polymorphic) cytochrome P450 enzymes in humans. Although high inter- and intraindividual variability in voriconazole pharmacokinetics have b...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2019.1632888
更新日期：2019-08-01 00:00:00
abstract：:Bioconjugation of therapeutic agents has been used as a selective drug delivery platform for many therapeutic areas. Bioconjugates are prepared by the covalent linkage of active compounds (small or large molecule) to a carrier molecule (lipids, proteins, peptides, carbohydrates, and polymers) through a chemical linker...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2020.1716784
更新日期：2020-02-01 00:00:00
abstract：:Acetaminophen (APAP, paracetamol, N-acetyl-p-aminophenol) is a widely used analgesic that is safe at therapeutic doses but is a major cause of acute liver failure (ALF) following overdose. APAP-induced hepatotoxicity is related to the formation of an electrophilic reactive metabolite, N-acetyl-p-benzoquinone imine (NA...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2014.982865
更新日期：2015-02-01 00:00:00
abstract：:Most foreign compounds, including nonnutrients in foods and vapors in air, undergo extensive metabolism before they are eliminated from the body. Included in this paper are discussions of the urinary clearance of various kinds of foreign compounds, the nonspecific enzymes that catalyze the formation of many metabolite...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602537908993901
更新日期：1979-01-01 00:00:00
abstract：:For patients undergoing cardiopulmonary bypass (CPB) during cardiac surgery, there are well-documented changes in the pharmacokinetics (PK) of commonly administered drugs. Although multiple factors potentially underpin these changes, there has been scant research attention on the impact of CPB to alter the activities ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2017.1417423
更新日期：2018-05-01 00:00:00
abstract：:Historically, failure rates in drug development are high; increased sophistication and investment throughout the process has shifted the reasons for attrition, but the overall success rates have remained stubbornly and consistently low. Only 8% of new entities entering clinical testing gain regulatory approval, indica...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2020.1726944
更新日期：2020-05-01 00:00:00
abstract：:The present paper has discussed available test systems for determination of the response of G-6-PD-deficient human erythrocytes to environmental agents. The limitations and advantages of each model have been examined, and the results of research using each model have been presented. The future development of suitable ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602538608998292
更新日期：1986-01-01 00:00:00
abstract：:Glycyrrhizic acid is widely applied as a sweetener in food products and chewing tobacco. In addition, it is of clinical interest for possible treatment of chronic hepatitis C. In some highly exposed subjects, side effects such as hypertension and symptoms associated with electrolyte disturbances have been reported. To...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1081/dmr-100104400
更新日期：2001-05-01 00:00:00
abstract：:Monkeys, especially macaques, including cynomolgus (Macaca fascicularis) and rhesus monkeys (Macaca mulatta), are frequently used in drug metabolism studies due to their evolutionary closeness to humans. Recently, numerous cytochrome P450 (P450 or CYP) cDNAs have been identified and characterized in cynomolgus and rhe...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.3109/03602532.2010.549492
更新日期：2011-08-01 00:00:00
abstract：:Like any other drugs, antiallergic medications can be associated with large inter- and intraindividual variability in their disposition. The best-documented examples belong to the H1 antihistamines. Variable drugs are more likely to show unpredictable therapeutic response with both increased risks of side effects and ...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/10837450902891485
更新日期：2009-01-01 00:00:00
abstract：:In summary, we have shown that steroid D-ring, but not steroid A-ring, glucuronide conjugates act at the level of the bile canaliculus to decrease bile-acid-dependent flow, initially; and subsequently, bile-acid-independent flow. These data indicate that glucuronide conjugates are not necessarily inactive; the present...
journal_title：Drug metabolism reviews
pub_type： 杂志文章
doi：10.3109/03602538308991419
更新日期：1983-01-01 00:00:00
abstract：:Cytochrome P450 (CYP) 2D6 is one of the most important enzymes involved in the metabolism of drugs. Multiple, clinically relevant, genetic variants of this gene have been identified and, among them, a gene deletion as well as multiplications of the gene. These large structural mutations in CYP2D6 occur at a relatively...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530600952206
更新日期：2007-01-01 00:00:00
abstract：:Psilocybin and psilocin are controlled substances in many countries. These are the two main hallucinogenic compounds of the "magic mushrooms" and both act as agonists or partial agonists at 5-hydroxytryptamine (5-HT)2A subtype receptors. During the last few years, psilocybin and psilocin have gained therapeutic releva...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602532.2016.1278228
更新日期：2017-02-01 00:00:00
abstract：:Hyperbilirubinemia may accompany harmful effects such as jaundice, brain dysfunction, and pharmacokinetic alterations of drugs. Clinical drugs are the important causes of hyperbilirubinemia, especially for patients with certain pathologic conditions or with genetic variations. This article reviews hyperbilirubinemic p...
journal_title：Drug metabolism reviews
pub_type： 杂志文章,评审
doi：10.1080/03602530802341133
更新日期：2008-01-01 00:00:00
