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Atherosclerosis
Published in George Feuer, Felix A. de la Iglesia, Molecular Biochemistry of Human Disease, 2020
George Feuer, Felix A. de la Iglesia
The amount of cholesterol released from LDL regulates the metabolism of the cell. The accumulation of exogenous cholesterol controls the reduction of the synthesis of endogenous cholesterol by inhibition of the synthesis of the CoA reductase, a key enzyme in cholesterol biosynthesis.384 Subsequently, the cell becomes dependent on exogenous cholesterol. The LDL-derived cholesterol increases the storage of cholesterol within the cell by activating acyl-CoA:cholesterol acyltransferase. This enzyme converts free cholesterol and triggers a feedback mechanism that affects the cell to stop producing new LDL receptors.
Xenobiotic Biotransformation
Published in Robert G. Meeks, Steadman D. Harrison, Richard J. Bull, Hepatotoxicology, 2020
Aldehyde reductase (EC 1.1.1.2.) catalyzes the reduction of carbonyl compounds. The enzyme is predominately cytosolic, with highest activity in kidney and significant activities in liver and brain. Carbonyl-containing substrates include aromatic aldehydes and ketones, aliphatic ketones, methyl, and unsaturated ketones. The metabolic functions of these enzymes are unknown, as are the physiological roles of aldehydes generated during intermediary metabolism. Since many aldehydes, particularly aldehyde derivatives of neurotransmitters, appear to be physiologically active, these enzymes may function to regulate endogenous aldehyde activity. At least three izoenzymes have been characterized. These include aldehyde reductase (the same isozyme as glucuronate reductase, mevaldate reductase, lactaldehyde reductase, and daunorubicin reductase), aldose reductase, and glycerol dehydrogenase.
Retinoic acid signaling in spermatogenesis and male (in)fertility
Published in Rajender Singh, Molecular Signaling in Spermatogenesis and Male Infertility, 2019
Dario Santos, Rita Payan-Carreira
RA has been shown to mitigate tissue susceptibility to oxidative stress by acting on some oxidative stress enzymes, such as SOD, CAT and glutathione reductase (101,102). RA impacts oxidative stress–mediated apoptosis in several tissues (103–105) and embryo differentiation (106). Redox-mediated apoptosis could be reverted in those tissues by the administration of all-trans-retinoic acid (ATRA). RA modulates antioxidant mechanisms also in spermatozoa (107). The action of RA in cell physiology is mediated by nuclear RA receptors and retinoid X receptors. Additionally, it has been described as a cytoplasmatic localization of receptors in bull and dog sperm, probably playing an active role in the cross talk with other signal transduction pathways (108).
Rational design of biodegradable sulphonamide candidates treating septicaemia by synergistic dual inhibition of COX-2/PGE2 axis and DHPS enzyme
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2022
Nada H. El-Dershaby, Soad A. El-Hawash, Shaymaa E. Kassab, Hoda G. Dabees, Ahmed E. Abdel Moneim, Ibrahim A. Abdel Wahab, Mohammad M. Abd-Alhaseeb, Mostafa M. M. El-Miligy
All the newly synthesised compounds were evaluated for their in vitro antibacterial activities against the human pathogens: Staphylococcus aureus (RCMB 0100183), Staphylococcus epidermidis (RCMB 0100183), Streptococcus mutans (RCMB 0100172), and Bacillus subtilis (RCMB 0100162) as examples of Gram-positive bacteria and Pseudomonas aeruginosa (RCMB 0100243), Escherichia coli (RCMB 010052), Salmonella typhi (RCMB 0100104), Shigella dysenteriae (RCMB 0100542) and Proteus vulgaris (RCMB 010085) as examples of Gram-negative bacteria using Ampicillin and levofloxacin as standard Gram-positive and Gram-negative antibacterial agents respectively[6] (Table 5, page S5 supplementary file) see experimental section. The results showed that, most of the tested compounds did not exhibit significant in vitro antibacterial activity, whereas compounds (5 b, 5i, 5j, 5k, 5 m, 5n, and 5o) displayed weak in vitro antibacterial activity this could be assigned to the fact that the investigated compounds were azo co-drugs. Hence, metabolic biotransformation by azo-reductase enzyme into their active metabolites is a requirement for expressing their activities.
Administration time-dependent effects of poly (I:C) on antioxidant and immune responses along the diurnal time scale in zebrafish
Published in Chronobiology International, 2022
Costanza Guidi, M. Ángeles Esteban, Francisco J. Sánchez-Vázquez, Luisa M. Vera
Polyinosinic:polycytidylic acid [poly (I:C)] is a synthetic analog of double-stranded RNA that mimics viral infections by interacting with the toll-like receptor (TLR) family and by eliciting a strong antiviral response in fish, which suggests that this molecule is used as an effective immunostimulatory adjuvant for mammal (Tewari et al. 2010) and fish (Kavaliauskis et al. 2015) vaccines. Immunostimulants like poly (I:C) contain pathogen-associated molecular patterns (PAMPs) that are recognized by specific receptors in host cells and, thus, trigger the immune response in fish species like zebrafish (Álvarez-Rodríguez et al. 2018). Poly (I:C) also induces oxidative stress in fish (Yue et al. 2018), similarly to the response observed after viral and bacterial infections when phagocytic cells destroy invading microorganisms to cause a respiratory burst that results in ROS formation (Schwarz 1996). ROS are oxidant compounds and are, therefore, counterbalanced by organisms’ antioxidant defenses, which include a network of compartmentalized antioxidative enzymes, such as superoxide dismutases, catalases, glutathione peroxidase glutathione reductases, among others (Staerck et al. 2017).
Evaluation of the drug–drug interaction potential for trazpiroben (TAK-906), a D2/D3 receptor antagonist for gastroparesis, towards cytochrome P450s and transporters
Published in Xenobiotica, 2021
Mitsuhiro Nishihara, Diane Ramsden, Suresh K. Balani
The reductase involved in [14C]trazpiroben metabolism was estimated based on the effect of reductase inhibitors using HLC. Typical reductase inhibitors were selected according to information in the literature (Rosemond et al.2004, Ramsden et al.2018). Phenobarbital, flufenamic acid, zopolrestat, chenodeoxycholic acid, and dexamethasone were used as aldo-keto reductase (AKR), 4-methylpyrazole was as an alcohol dehydrogenase inhibitor, disulphiram was as an aldehyde dehydrogenase inhibitor, quercetin and menadione were as short-chain dehydrogenase/reductase (SDR) and carbonyl reductase (CR) inhibitors, and dicumarol was as a quinone reductase inhibitor, respectively. The remaining activity was calculated as the percentage to the total radioactivity of the M23 peak in the sample with each inhibitor when the corresponding percentage in each control sample was regarded as 100%. The inhibition was calculated using the following equation: samp is the percentage to the total radioactivity of the M23 peak in the sample with each inhibitor (%) and PRcont is the percentage to the total radioactivity of the M23 peak in each control sample (%).