Basic Pharmaceutical Sciences, West Virginia University, 1 Medical Center Drive, P.O. Box 9530, Morgantown, WV, 26506, USA.
Published: February 2014
AI Article Synopsis
Article Abstract
Cytochrome P450 enzymes play a key role in the metabolism of pharmaceutical agents. To determine metabolite toxicity, it is necessary to obtain P450 metabolites from various pharmaceutical agents. Here, we describe a bioreactor that is made by immobilizing cytochrome P450 2C9 (CYP2C9) to a poly(methyl methacrylate) surface and, as an alternative to traditional chemical synthesis, can be used to biosynthesize P450 metabolites in a plug flow bioreactor. As part of the development of the CYP2C9 bioreactor, we have studied two different methods of attachment: (1) coupling via the N-terminus using N-hydroxysulfosuccinimide 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide and (2) using the Ni(II) chelator 1-acetato-4-benzyl-triazacyclononane to coordinate the enzyme to the surface using a C-terminal histidine tag. Additionally, the propensity for metabolite production of the CYP2C9 proof-of-concept bioreactors as a function of enzyme attachment conditions (e.g., time and enzyme concentration) was examined. Our results show that the immobilization of CYP2C9 enzymes to a PMMA surface represents a viable and alternative approach to the preparation of CYP2C9 metabolites for toxicity testing. Furthermore, the basic approach can be adapted to any cytochrome P450 enzyme and in a high-throughput, automated process.
Clinical and Experimental Therapeutics, College of Pharmacy, University of Georgia, Augusta, GA, 30912, USA; Charlie Norwood VA Medical Center, Augusta, GA, 30912, USA; Department of Medicine, Medical College of Georgia, Augusta University, Augusta, GA, 30912, USA. Electronic address:
Emerging evidence suggests that lipid-laden macrophages (LLM) participate in lung damage in various clinical conditions. However, the mechanisms involved in LLM formation are not fully understood. In this study, we aimed to investigate the link between reactive oxygen species (ROS) and LLM formation.
Background: Elinzanetant is a dual neurokinin-1,3 receptor antagonist in development for the treatment of menopausal vasomotor symptoms. The objectives of these studies were to characterize the mass balance and biotransformation of elinzanetant.
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Sodium dehydroacetate (DHA-Na), a widely used preservative, can induce sex-differentiated coagulation disorders primarily resulting from its metabolism. However, the underlying mechanisms remain poorly understood. Here, we identified several Cytochrome P450 (CYP450) sub-enzymes involved in sex differences related to DHA-Na metabolism, along with two related DHA-Na metabolites.
State Key Laboratory of Crop Genetics and Germplasm Enhancement, College of Horticulture, Nanjing Agricultural University, Weigang Street No.1, Nanjing, 210095, China.
A dwarf mutant with short branches (csdf) was identified from EMS-induced mutagenesis. Bulked segregant analysis sequencing and map-based cloning revealed CsKAO encoding ent-kaurenoic acid oxidase as the causal gene. Plant architecture is the primary target of artificial selection during domestication and improvement based on the determinate function for fruit yield.
The effects of chlormequat chloride, a typical plant growth regulator, on the medicinal herb Corydalis yanhusuo were investigated. A standardized field experiment was conducted to investigate the molecular mechanisms and variations in active compounds resulting from chlormequat chloride treatment. Samples of C.
