Cytochrome P450-Dependent Metabolism of Drugs and Carcinogens in Skin
Rhoda G. M. Wang, James B. Knaak, Howard I. Maibach in Health Risk Assessment, 2017
Depending on the particular reaction and the nature of various unstable intermediates, different types of Phase I reactions can occur in skin.18 However, in a typical Phase I reaction, hydroxylation of the substrate occurs at a carbon atom. In the first step, the substrate binds to the protein moiety of the oxidized P450, followed by one electron reduction of the heme iron (Fe3+) provided by NADPH-P450 reductase. The reduced P450-substrate complex, thus formed, binds to molecular oxygen and utilizes another electron from NADPHP450 reductase. During this process, the substrate is attacked by the oxygen molecule and thereby one oxygen atom is inserted into the substrate which is released from the enzyme as the hydroxylated product, while the second oxygen atom yields water. Based on this process, this enzyme reaction has been termed as a “mixed-function oxidase”- or a “monooxygenase”- reaction.
Regulation of Eosinophil Mediator Release by Adhesion Molecules
Bruce S. Bochner in Adhesion Molecules in Allergic Disease, 2020
When challenged with an appropriate stimulus, eosinophils, like neutrophils and monocytes, produce oxygen-derived free radicals. In fact, the oxidative products of eosinophils include superoxide anion, hydroxyl radicals, H2O2, and singlet oxygen (47,48). When membrane-associated oxidase is activated, it catalyzes the single electron reduction of oxygen using NADPH as an electron donor. The product of the NADPH:O2 oxidoreductase-catalyzed reaction is the superoxide anion, a powerful oxidizing and reducing agent with bactericidal properties (49). Superoxide anions can undergo spontaneous oxidation to 02, or reduction to H2O2 in the presence of superoxide dismutase. The H2O2 produced by eosinophils shows potent biological activity in conjunction with EPO, as described above. Furthermore, in the presence of ferrous ions, the superoxide anion and H2O2 interact to form the membrane-perturbating hydroxy radical, a reactive and unstable oxidizing species. It is noteworthy that the activity of the NADPH:O2 oxidoreductase is significantly higher in eosinophils than it is in neutrophils (50,51), which may be relevant to the pathophysiology of eosinophil-mediated diseases such as bronchial asthma (52).
Benzene Metabolism (Toxicokinetics and the Molecular Aspects of Benzene Toxicity)
Muzaffer Aksoy in Benzene Carcinogenicity, 2017
A number of agents are thought to exert their toxic effects via oxygen reduction leading to the production of superoxide, hydrogen peroxide, hydroxyl radical, and perhaps singlet oxygen.83 These reactions may be enzymatic or nonenzymatic. NADPH oxidase is an enzyme activity in which the mixed function oxidase reduces oxygen making use of reducing equivalents from NADPH. This may happen in the absence of a substrate or may be an ongoing activity of some types of cytochrome P-450 not involved in metabolizing the specific substrate undergoing metabolism. Lorentzen et al.84 demonstrated that 6-hydroxybenzo[a]pyrene in solution autoxidizes to form 6,12-, 1,6-, and 3,6-benzo[a]pyrene diones in the absence of any enzymes. During the formation of these metabolites, oxygen was consumed and H2O2 was generated. Lorentzen et al.85,86 showed that these metabolites were toxic to cells in culture in the presence of oxygen. The relationship of these studies to benzene metabolism and toxicity lies in the necessity for benzene to be metabolized as far as the stage of dihydroxylated metabolites, especially catechol, before autoxidation can play a role.
Alcohol quantification: recent insights into amperometric enzyme biosensors
Published in Artificial Cells, Nanomedicine, and Biotechnology, 2018
Vinita Hooda, Vikas Kumar, Anjum Gahlaut, Vikas Hooda
The oxidation reaction of alcohols by AOX is irreversible in nature, owing to the strong oxidising character of O2. The enzymatically active form of AOX is a homo-octameric flavoenzyme having size approximately 600 kDa and bound with a flavin adenine dinucleotide which serves as a cofactor to the enzyme [15]. This flavoenzyme consists of eight identical subunits which are sequentially arranged in a quasi-cubic arrangement. In the catalytic process, first there is reduction of the cofactor i.e. FAD into the hydrogenated form (FADH2) and then again its reoxidation to the native form. The standard pathways to monitor a reaction catalysed by an oxidase enzyme have been performed by evaluating either the consumption of O2 or the production of H2O2.
Biological and Immunological Aspects of Iron Deficiency Anemia in Cancer Development: A Narrative Review
Published in Nutrition and Cancer, 2018
Fatema Zohora, Katayoon Bidad, Zahra Pourpak, Mostafa Moin
HO-1 that is robustly expressed by healthy cells and contains stress response element (113). HO-1 is an inducible cytoprotective catalytic enzyme that catalyses heme degradation and produces free iron, antioxidant biliverdin/bilirubin, and anti-inflammatory carbon monoxide (CO) and thereby protect cells against oxidative stress from external environment (114). In an in vitro study, HO-1 has been reported for its significant anti-inflammatory and anti-catabolic roles in the pathology of Osteoarthritis (115). Lai et al. studied with HCT-116 human colon adenocarcinoma cells and reported that the cells without adequate iron were unable to express the HO-1 completely in response to Cadmium mediated injury (116). But in 2015, Inoue et al. studied with iron deficient BALB mice and reported that there was an increased expression of HO-1 as a defense against iron deficiency-induced oxidative stress (37). Iron is essential for HO-1 gene expression which is initiated by a signaling oxidant (Superoxide). This signaling oxidant is produced by iron atoms in heme of NADPH oxidase (NOX) system through transferring electrons from NOX to molecular oxygen (116). Therefore, IDA may reduce this signaling pathway and diminish the cytoprotective role of HO-1.
Hyperuricemia and prognosis of acute ischemic stroke in diabetic patients
Published in Neurological Research, 2019
Ping Wang, Xinyan Li, Chaoming He, Yun Zhai, Hongwei Sun, Yu Zhang, Hong Wang, Yuna Wang, Jingbo Zhao, Ying Tang
Oxidative stress is a major factor attributed to neuronal injury generated by ischemic stroke [20]. As a natural antioxidant, physiological UA could protect human brains from oxidative stress and inflammatory process after onset of ischemic stroke [1,21,22]. However, UA did not improve clinical outcome of AIS in the present study. Simultaneously, an elevated level of serum UA has been reported as a risk factor of ischemic stroke [2,3]. UA is the end-product of purine metabolism. The two main reactions of UA production convert hypoxanthine to xanthine and then xanthine to UA through xanthine oxidoreductase. Xanthine oxidoreductase contains two inter-convertible forms, named xanthine dehydrogenase and xanthine oxidase [23]. Xanthine oxidase generates other reactive oxygen species as by-products and thus increases oxidative stress. In patients with AIS, xanthine oxidase is expressed more pronounced than healthy subjects [21,23], as the major physiological mechanism underlying why elevated serum UA exerts negative effects on ischemic stroke. A clinical trial indicated that xanthine oxidase inhibition could improve long-term outcome of AIS by reducing serum UA level and oxidative stress [24]. Furthermore, HUA harboured a higher risk for AIS. Theoretically, first, precipitation of UA on the blood vessel wall undermines endothelial function [25]; second, HUA promotes inflammatory response [25]; third, HUA enhances insulin resistance [26]; fourth, HUA spurs the development of atherosclerosis and thrombosis [4].
Related Knowledge Centers
- Biochemistry
- Catalysis
- Enzyme
- Hydrogen Peroxide
- Monoamine Oxidase
- Xanthine Oxidase
- Redox
- Allotropes of Oxygen
- Hydrogen
- Oxidoreductase