Liver microsomal mixed-function oxidase activities were determined in female Sprague-Dawley rats after 3 weeks of ethanol feeding and for up to 10 days after withdrawal. Ethanol (36% of total calories) was administered in a high fat liquid diet and was replaced isocalorically by carbohydrates in controls. Chronic ethanol feeding similarly enhanced both microsomal cytochrome P-450 content and benzphetamine N-demethylase activity, per mg of protein, and resulted in a disproportionate increase in both aniline hydroxylase and 7-ethoxycoumarin O-deethylase activities. A 6- to 7-day withdrawal period was apparently necessary for the overall disappearance of these effects of ethanol. Marked differences, however, were seen in the time courses of return of these variables to control levels, as also indicated by changes, during this period and specially during the first 24 hr after withdrawal, in the apparent molar activity of the microsomal fraction with the three substrates tested. The results were interpreted as indicating that the distinct ethanol-inducible cytochrome P-450 isozyme, with a high specific activity toward aniline, undergoes a very rapid turnover in liver microsomes. Induction of another form of cytochrome P-450, differing from the former by its slower turnover rate, would explain the induction by ethanol of 7-ethoxycoumarin O-deethylase activity. The withdrawal of ethanol was followed by a rapid but transient increase in benzphetamine N-demethylase activity above the ethanol-induced level, at a time when other activities were rapidly declining. This could suggest that the microsomal content of other cytochrome P-450 isozyme(s), with high specific activity toward this substrate, would also be temporarily altered during ethanol withdrawal. Important alterations in microsomal cytochrome P-450-dependent mixed-function oxidase activities occurred during the initial 24-hr period of withdrawal, even in the absence of a change in microsomal cytochrome P-450 content, indicating that the effects of chronic ethanol ingestion on hepatic drug-metabolizing enzyme activities may also be highly dependent on the proximity of ethanol intake.
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http://dx.doi.org/10.1016/0006-2952(85)90497-6 | DOI Listing |
Nat Commun
January 2025
Brazilian Biorenewables National Laboratory, Brazilian Center for Research in Energy and Materials, Campinas, SP, Brazil.
Fatty acid peroxygenases have emerged as promising biocatalysts for hydrocarbon biosynthesis due to their ability to perform C-C scission, producing olefins - key building blocks for sustainable materials and fuels. These enzymes operate through non-canonical and complex mechanisms that yield a bifurcated chemoselectivity between hydroxylation and decarboxylation. In this study, we elucidate structural features in P450 decarboxylases that enable the catalysis of unsaturated substrates, expanding the mechanistic pathways for decarboxylation reaction.
View Article and Find Full Text PDFToxicol Mech Methods
January 2025
Department of Pharmacology, Shri Vishnu College of Pharmacy, Vishnupur, Bhimavaram, Andhra Pradesh, India-534202.
The harmful by-product of paracetamol is known as N-Acetyl-p-benzoquinoneimine, (NAPQI). When paracetamol is given at therapeutic dosages or in excess, it undergoes Phase I metabolism in the liver via Cytochrome P-450 2E1 (CYP2E1), and then it produces NAPQI. Previous studies reported that a non-ionic surfactant known as Brij 35 (Polyoxyethylene lauryl ether) has been shown to be an effective inhibitor of CYP2E1 and P-glycoprotein (P-gp).
View Article and Find Full Text PDFJ Clin Endocrinol Metab
January 2025
Division of Pediatric Endocrinology, Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX 75390, USA.
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disease that manifests clinically in varying forms depending on the degree of enzyme deficiency. CAH is most commonly caused by 21-hydroxylase deficiency (21OHD) due to mutations in the CYP21A2 gene. Whereas there is a spectrum of disease severity, 21OHD is generally categorized into 3 forms.
View Article and Find Full Text PDFBiotechnol J
January 2025
Beijing Advanced Innovation Center for Soft Matter Science and Engineering, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, China.
Terpenoids are widely distributed in nature and have various applications in healthcare products, pharmaceuticals, and fragrances. Despite the significant potential that terpenoids possess, traditional production methods, such as plant extraction and chemical synthesis, face challenges in meeting current market demand. With the advancement of synthetic biology and metabolic engineering, it becomes feasible to construct efficient microbial cell factories for large-scale production of terpenoids.
View Article and Find Full Text PDFJ Nanobiotechnology
January 2025
Key Laboratory of Human Genetics and Environmental Medicine, Xuzhou Medical University, Xuzhou, 221004, China.
Fullerenols, a water-soluble polyhydroxy derivative of fullerene, hold promise in medical and materials science due to their unique properties. However, concerns about their potential embryotoxicity remain. Using a pregnancy mouse model and metabolomics analysis, our findings reveal that fullerenols exposure during pregnancy not only significantly reduced mice placental weight and villi thickness, but also altered the classes and concentrations of metabolites in the mouse placenta.
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