AI Article Synopsis
- A human cDNA clone for the cytochrome P4502C9 enzyme was isolated from a liver library, and its expression in COS cells revealed a 55 kDa enzyme capable of methylhydroxylating tolbutamide.
- The enzyme showed a Km of 131.7 µM for tolbutamide, consistent with human liver microsomes, and also catalyzed the 4-hydroxylation of phenytoin.
- Inhibition studies indicated that phenytoin inhibited tolbutamide metabolism competitively, while sulphaphenazole was a strong inhibitor for both reactions, suggesting a single isozyme mediates these hydroxylation processes in the liver.
Article Abstract
A human cytochrome P4502C9 cDNA clone has been isolated from a human liver bacteriophage Lambda gt11 library using oligonucleotide probes. Expression of the 1762 base pair cDNA in COS cells demonstrated that the encoded enzyme has a molecular mass of 55 kDa as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The expressed enzyme catalysed the methylhydroxylation of tolbutamide with an apparent Km of 131.7 microM, similar to that observed in human liver microsomes. P4502C9 also catalysed the 4-hydroylation of phenytoin, and inhibition experiments demonstrated that phenytoin was a competitive inhibitor of tolbutamide hydroxylation with an apparent Ki of 19.1 microM. Sulphaphenazole was a potent inhibitor of the expressed enzyme with respect to both tolbutamide and phenytoin hydroxylations. These data demonstrate that a single isozyme can catalyse the hydroxylations of both tolbutamide and phenytoin, and suggest that both reactions are mediated by the same isozyme(s) of cytochrome P450 in human liver.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/0006-291x(91)91680-b | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Integrative proteogenomic analyses provide novel interpretations of type 1 diabetes risk loci through circulating proteins.
Diabetes
January 2025
Division of Biostatistics, Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Circulating proteins may be promising biomarkers or drug targets. Leveraging genome-wide association studies of type 1 diabetes (18,942 cases and 501,638 controls of European ancestry) and circulating protein abundances (10,708 European ancestry individuals), Mendelian randomization analyses were conducted to assess the associations between circulating abundances of 1,560 candidate proteins and the risk of type 1 diabetes, followed by multiple sensitivity and colocalization analyses, horizontal pleiotropy examinations, and replications. Bulk tissue and single-cell gene expression enrichment analyses were performed to explore candidate tissues and cell types for prioritized proteins.
View Article and Find Full Text PDFAssociation of gut microbiota and gut metabolites and adverse outcomes in biliary atresia: A longitudinal prospective study.
Hepatol Commun
November 2024
Paediatric Liver, GI and Nutrition Centre and Mowatlabs, King's College Hospital, London, UK.
Background: The Kasai portoenterostomy (KPE) aims to re-establish bile flow in biliary atresia (BA); however, BA remains the commonest indication for liver transplantation in pediatrics. Gut microbiota-host interplay is increasingly associated with outcomes in chronic liver disease. This study characterized fecal microbiota and fatty acid metabolites in BA.
View Article and Find Full Text PDFSpatial mapping of the HCC landscape identifies unique intratumoral perivascular-immune neighborhoods.
Hepatol Commun
November 2024
Human Immunology Laboratory, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, New South Wales, Australia.
Background: HCC develops in the context of chronic inflammation; however, the opposing roles the immune system plays in both the development and control of tumors are not fully understood. Mapping immune cell interactions across the distinct tissue regions could provide greater insight into the role individual immune populations have within tumors.
Methods: A 39-parameter imaging mass cytometry panel was optimized with markers targeting immune cells, stromal cells, endothelial cells, hepatocytes, and tumor cells.
Serum amyloid P (PTX2) attenuates hepatic fibrosis in mice by inhibiting the activation of fibrocytes and HSCs.
Hepatol Commun
November 2024
Department of Medicine, University of California, San Diego, La Jolla, California, USA.
Background: Liver fibrosis is caused by chronic toxic or cholestatic liver injury. Fibrosis results from the recruitment of myeloid cells into the injured liver, the release of inflammatory and fibrogenic cytokines, and the activation of myofibroblasts, which secrete extracellular matrix, mostly collagen type I. Hepatic myofibroblasts originate from liver-resident mesenchymal cells, including HSCs and bone marrow-derived CD45+ collagen type I+ expressing fibrocytes.
View Article and Find Full Text PDFStratification of Experimental LPS-Induced Systemic Inflammatory Response by Expression Level of Hif1a and NFkb Genes.
Bull Exp Biol Med
January 2025
Avtsyn Research Institute of Human Morphology, Petrovsky National Research Center of Surgery, Moscow, Russia.
It was previously found that the severity of LPS-induced systemic inflammatory response (SIRS) in rats is determined by resistance to hypoxia and the level of Hif1a expression. Individual differences in the level of Hif1a and NFkb expression in the liver were studied in relation to the severity of inflammatory and immune reactions in LPS-induced SIRS in rats without previous placement in a ventilated decompression chamber. During the early periods after SIRS modeling, rats with high expression of the Hif1a and NFkb genes associated with increased expression of pro- and anti-inflammatory cytokines are identified.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!