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cytochrome P450 reductase

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https://www.readbyqxmd.com/read/29328974/novel-approach-for-evaluating-pharmaceuticals-toxicity-using-daphnia-model-analysis-of-the-mode-of-cytochrome-p450-generated-metabolite-action-after-acetaminophen-exposure
#1
Ryeo-Ok Kim, Min-A Jo, Jinhaeng Song, Il-Chan Kim, Seokjoo Yoon, Woo-Keun Kim
Because of its widespread use, the pharmaceutical acetaminophen (APAP) is frequently detected in aquatic environments. APAP can have serious physiological effects, such as reduced reproduction, low growth rates, and abnormal behavior, in aquatic organisms. However, the methods available for evaluation of the aquatic toxicity of APAP are of limited usefulness. The present study aimed to develop reliable and sensitive markers for evaluation of APAP toxicity using Daphnia as a model organism. We focused on N-acetyl-p-benzoquinoneimine (NAPQI) production from APAP via cytochrome P450 metabolism because NAPQI causes APAP toxicity...
December 30, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29327817/ketonization-of-proline-residues-in-the-peptide-chains-of-actinomycins-by-a-4-oxoproline-synthase
#2
Siamak Semsary, Ivana Crnovčić, Ronja Driller, Joachim Vater, Bernhard Loll, Ullrich Keller
X-type actinomycins (Acms) contain 4-hydroxyproline (Acm X0) or 4-oxoproline (Acm X2) in their ß-pentapeptide lactone rings whereas their α-ring contains proline. We demonstrate that these Acms are formed through asymmetric condensation of Acm half molecules (Acm halves) containing proline with 4-hydroxyproline- or 4-oxo-proline-containing Acm halves. In turn we show - using an artificial Acm half analogue (PPL 1) with proline in its peptide chain - its conversion into the 4-hydroxyproline and 4-oxoproline-containing Acm halves, PPL 0 and PPL 2, in mycelial suspensions of Streptomyces antibioticus...
January 12, 2018: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29326229/genomic-understanding-of-an-infectious-brain-disease-from-the-desert
#3
Leandro F Moreno, Abdalla A O Ahmed, Balázs Brankovics, Christina A Cuomo, Steph B J Menken, Saad J Taj-Aldeen, Hani Faidah, J Benjamin Stielow, Marcus de M Teixeira, Francesc X Prenafeta-Boldú, Vania A Vicente, Sybren de Hoog
Rhinocladiella mackenziei accounts for the majority of fungal brain infections in the Middle East and is restricted to the arid climate zone between Saudi Arabia and Pakistan. Neurotropic dissemination caused by this fungus has been reported in immunocompromised, but also immunocompetent individuals. If untreated, the infection is fatal. Outside of humans, the environmental niche of R. mackenziei is unknown, and the fungus has been only cultured from brain biopsies. In this paper we describe the whole genome re-sequencing of two Rhinocladiella mackenziei strains from patients in Saudi Arabia and Qatar...
January 11, 2018: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/29317847/pharmacogenetic-guidance-individualized-medicine-promotes-enhanced-pain-outcomes
#4
Lisa Lynn Dragic, Erica L Wegrzyn, Michael E Schatman, Jeffrey Fudin
The use of pharmacogenomics has become more prevalent over the past several years in treating many disease states. Several cytochrome P450 enzymes play a role in the metabolism of many pain medications including opioids and antidepressants. Noncytochrome P450 enzymes such as methylenetetrahydrofolate reductase (MTHFR) and catechol-O-methyl transferase (COMT) also play a role in the explanation of opioid dosage requirements as well as in response to certain antidepressants. We present the case of a patient with reduced COMT and MTHFR expression treated with leucovorin 10 mg daily for the management of chronic pain...
2018: Journal of Pain Research
https://www.readbyqxmd.com/read/29288567/isothiocyanates-and-xenobiotic-detoxification
#5
REVIEW
Ahmad Faizal Abdull Razis, Nattaya Konsue, Costas Ioannides
The potential of isothiocyanates to antagonise the carcinogenicity of structurally-diverse chemicals has been established in animals. A feasible mechanism of action involves protecting DNA by reducing the availability of the genotoxic metabolites of chemical carcinogens by either inhibiting their generation and/or stimulating their detoxification. In vivo as well as in vitro studies conducted in rat/human primary hepatocytes and precision-cut tissue slices have revealed that isothiocyanates can impair cytochrome P450 activity, including the CYP1 family which is the most active in the bioactivation of carcinogens, by virtue of being mechanism-based inactivators...
December 30, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/29286073/proteasome-inhibition-protects-against-diet-induced-gallstone-formation-through-modulation-of-cholesterol-and-bile-acid-homeostasis
#6
Eun-Ji Lee, Min Hee Kim, Ye-Ryung Kim, Joo-Won Park, Woo-Jae Park
Gallstone disease is one of the most prevalent and costly gastrointestinal disorders worldwide. Gallstones are formed in the biliary system by cholesterol secretions in bile, which result from excess cholesterol, a deficiency in bile salts or a combination of the two. The present study examined the effects of proteasome inhibition on gallstone formation using the proteasome inhibitors bortezomib (BT) and carfilzomib (CF). C57BL/6J mice were fed a lithogenic diet to generate gallstones and injected with BT or CF for 12 weeks...
December 15, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29285101/proteomic-changes-of-cd4-cd25-forkhead-box-p3-regulatory-t-cells-in-a-30-day-rat-model-of-sepsis-survival
#7
Yuxia Jiao, Siqi Tan, Junyu Xiong
Sepsis is defined as life threatening organ dysfunction arising from a dysregulated host response to infection. The outcomes of sepsis include early mortality, delayed mortality and recovery, and depend on the inflammatory response. Previous studies have demonstrated that regulatory T cells (Tregs) are important in determining the outcome of sepsis, as their suppressive function serves a role in maintaining immune homeostasis. However, Treg-mediated immunosuppression during the course of sepsis remains unclear and little is known about the survival of patients following diagnosis...
December 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29277994/the-choreography-of-the-reductase-and-p450bm3-domains-towards-electron-transfer-is-instigated-by-the-substrate
#8
Kshatresh Dutta Dubey, Sason Shaik
The driving force for the electron transfer (ET) step in the catalytic cycle of cytochrome P450BM3, is investigated using three sets of 1 µs molecular dynamic simulations for the resting state of P450 in complex with the flavin (FMN) in the reductase domain. These sets involve: (i) substrate-free (SF), (ii) substrate (N-palmitoyl glycine, i.e NPG)-bound (SB), and (iii) SB with the semiquinone radical-anion (SQ-) of FMN. Starting from the X-ray structure of the SF heme domain, we observe that the α1 helix (of the reductase) and the C helix (of the heme) undergo reorientation to a parallel orientation, which is the thermochemically stable form...
December 26, 2017: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/29277707/the-in-vitro-metabolism-of-11%C3%AE-hydroxyprogesterone-and-11-ketoprogesterone-to-11-ketodihydrotestosterone-in-the-backdoor-pathway
#9
Desmaré van Rooyen, Rachelle Gent, Lise Barnard, Amanda C Swart
Increased circulating 11β-hydroxyprogesterone (11OHP4), biosynthesised in the human adrenal, is associated with 21-hydroxylase deficiency in congenital adrenal hyperplasia. 17α-hydroxyprogesterone levels are also increased, with the steroid's metabolism to dihydrotestosterone in the backdoor pathway contributing to hyperandrogenic clinical conditions. In this study we investigated the in vitro biosynthesis and downstream metabolism of 11OHP4. Both cytochrome P450 11β-hydroxylase and aldosterone synthase catalyse the biosynthesis of 11OHP4 from progesterone (P4) which is converted to 11-ketoprogesterone (11KP4) by 11β-hydroxysteroid dehydrogenase type 2, while type 1 readily catalysed the reverse reaction...
December 23, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29276819/stabilization-of-the-reductase-domain-in-the-catalytically-self-sufficient-cytochrome-p450bm3-via-consensus-guided-mutagenesis
#10
Gloria Saab-Rincon, Hanan Alwaseem, Valeria Guzmán-Luna, Leticia Olvera, Rudi Fasan
The multi-domain, catalytically self-sufficient cytochrome P450 BM-3 from Bacillus megaterium (P450BM3) constitutes a versatile enzyme for the oxyfunctionalization of organic molecules and natural products. However, the limited stability of the diflavin reductase domain limits the utility of this enzyme for synthetic applications. In this work, a consensus-guided mutagenesis approach was applied to enhance the thermal stability of the reductase domain of P450BM3. Upon phylogenetic analysis of a set of distantly related P450s (% identity > 38%), a total of 14 amino acid substitutions were identified and evaluated in terms of their stabilizing effect relative to the wild-type reductase domain...
December 24, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29274033/supplementation-with-an-insoluble-fiber-obtained-from-carob-pod-ceratonia-siliqua-l-rich-in-polyphenols-prevents-dyslipidemia-in-rabbits-through-sirt1-pgc-1%C3%AE-pathway
#11
María Valero-Muñoz, Sandra Ballesteros, Baltasar Ruiz-Roso, Lourdes Pérez-Olleros, Beatriz Martín-Fernández, Vicente Lahera, Natalia de Las Heras
PURPOSE: To investigate the mechanism implicated in the effect of an insoluble fiber (obtained from carob pod) rich in polyphenols (IFCP) in lipid metabolism in the liver. METHODS: Male New Zealand rabbits were fed with the following diets for 8 weeks: control diet (CT group), dyslipidemic diet supplemented with 0.5% cholesterol + 14% coconut oil (DL group) and dyslipidemic diet containing 0.5% cholesterol + 14% coconut oil plus 3% IFCP (DL + IFCP group)...
December 22, 2017: European Journal of Nutrition
https://www.readbyqxmd.com/read/29258871/phylogenetic-and-functional-characterization-of-ten-p450-genes-from-the-cyp6ae-subfamily-of-helicoverpa-armigera-involved-in-xenobiotic-metabolism
#12
Yu Shi, Huidong Wang, Zhi Liu, Shuwen Wu, Yihua Yang, René Feyereisen, Yidong Wu
The cotton bollworm, Helicoverpa armigera, is a generalist herbivore widely distributed over the world and is a major lepidopteran pest on cotton. Studies, especially from Asia, show that it relies on cytochrome P450 monooxygenases with broad substrate specificities to protect itself from pesticides. The number of P450s may have expanded in the processes of coping with the wide diversity of phytochemicals that the insect encounters among its numerous host plants. In order to examine the metabolic capabilities of these P450s, we focused here on all ten P450s of the Helicoverpa armigera CYP6AE subfamily, which can be easily induced by plant toxins and pyrethroids...
December 16, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29233819/characterization-of-interactions-among-cyp1a2-cyp2b4-and-nadph-cytochrome-p450-reductase-identification-of-specific-protein-complexes
#13
John Patrick Connick, James R Reed, Wayne L Backes
Cytochromes P450 catalyze oxygenation reactions via interactions with their redox partners. However, other proteins, particularly other P450s, also have been shown to form complexes that modulate P450 function. Previous studies showed that CYP1A2 and CYP2B4 form a complex when reconstituted into phospholipid vesicles; however, details of the interactions among the P450s and NADPH-cytochrome P450 reductase have not been fully characterized. The goal of this study was to examine P450 complex formation in living cells, using bioluminescence resonance energy transfer (BRET)...
December 12, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29219229/characterisation-of-cyp102a25-from-b-marmarensis-and-cyp102a26-from-p-halophilus-p450-homologues-of-bm3-with-preference-towards-hydroxylation-of-medium-chain-fatty-acids
#14
Joanne L Porter, Jack Manning, Selina Sabatini, Michele Tavanti, Nicholas J Turner, Sabine L Flitsch
Cytochrome P450 monooxgenases are highly desired biocatalysts due to their ability to catalyse a wide variety of chemically challenging C-H activation reactions. The CYP102A subfamily of enzymes are natural catalytically self-sufficient proteins consisting of a haem and FMN-FAD reductase domain fused in a single component system. They catalyse the oxygenation of saturated and unsaturated fatty acids to produce primarily ω-1, ω-2 and ω-3 hydroxy acids. These monooxygenases have broad applications in biotechnology however, their substrate range is still limited and there is a continued need to add diversity to this class of biocatalysts...
December 8, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/29207507/zinc-ameliorate-oxidative-stress-and-hormonal-disturbance-induced-by-methomyl-abamectin-and-their-mixture-in-male-rats
#15
Sameeh A Mansour, Mostafa A Abbassy, Hassan A Shaldam
Exposure to mixtures of toxicants (e.g., pesticides) is common in real life and a subject of current concern. The present investigation was undertaken to assess some toxicological effects in male rats following exposure to methomyl (MET), abamectin (ABM), and their combination (MET+ABM), and to evaluate the ameliorative effect of zinc co-administration. Three groups of rats were designated for MET, ABM, and the mixture treatments. Three other groups were designated for zinc in conjunction with the pesticides...
December 3, 2017: Toxics
https://www.readbyqxmd.com/read/29201176/in-vivo-and-in-vitro-studies-on-the-roles-of-p38-mitogen-activated-protein-kinase-and-nadph-cytochrome-p450-reductase-in-alzheimer-s-disease
#16
Yunyi Yao, Jin-Zhong Huang, Liang Chen, Yingqi Chen, Xianhong Li
Alzheimer's disease (AD) is a chronic neurodegenerative disease with an increasing morbidity rate. As one of the most important signaling pathways that responds to inflammation and degeneration, the p38 mitogen-activated protein kinase (MAPK) signaling pathway is active in the cortexes of AD mice. At the cellular level the same effect can be observed with p38 MAPK when induced by amyloid β (Aβ)1-42, a 42-residue Aβ fragment. Inhibition of p38 MAPK in the present study protected SH-SY5Y cells from the toxicity of Aβ1-42, and alleviated the formation of senile plaques and cognitive impairment in AD mice...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29200270/arachidonic-acid-metabolism-by-human-cardiovascular-cyp2j2-is-modulated-by-doxorubicin
#17
William R Arnold, Javier L Baylon, Emad Tajkhorshid, Aditi Das
Doxorubicin (DOX) is a chemotherapeutic that is used in the treatment of a wide variety of cancers. However, it causes cardiotoxicity partly due to the formation of reactive oxygen species (ROS). CYP2J2 is a human cytochrome P450 that is highly expressed in cardiomyocytes. It converts arachidonic acid (AA) into four different regioisomers of epoxyeicosatrienoic acids (EETs). Using kinetic analyses we show that AA metabolism by CYP2J2 is modulated by DOX. We show that cytochrome P450 reductase (CPR), the redox partner of CYP2J2, metabolizes DOX to 7-deoxydoxorubicin aglycone (7-de-aDOX)...
December 4, 2017: Biochemistry
https://www.readbyqxmd.com/read/29199886/mycosynthesis-of-bactericidal-silver-and-polymorphic-gold-nanoparticles-physicochemical-variation-effects-and-mechanism
#18
Dheeraj Kumar Singh, Jitendra Kumar, Vijay Kumar Sharma, Satish Kumar Verma, Arti Singh, Puja Kumari, Ravindra Nath Kharwar
AIM: Extracellular synthesis of silver and gold nanoparticles using aqueous cell-free filtrate (CFF) of endophytic Chaetomium globosum and characterization of its bioactive proteins. METHODS: Temperature and pH gradients were used to assess their effects on dimensions of NPs. NPs were tested in vivo for antibacterial activity. MALDI-TOF-MS/MS was used for characterization of CFF proteins. RESULTS: Fungal CFF fabricated nanoparticles of various shape under varied physicochemical conditions...
January 2018: Nanomedicine
https://www.readbyqxmd.com/read/29196293/the-catabolism-of-3-6-dichlorosalicylate-is-initiated-by-the-cytochrome-p450-monooxygenase-system-dsmabc-in-rhizorhabdus-dicambivorans-ndbn-20
#19
Na Li, Li Yao, Qin He, Jiguo Qiu, Dan Cheng, Derong Ding, Qing Tao, Jian He, Jiandong Jiang
The degradation of the herbicide dicamba is initiated by demethylation to form 3,6-dichlorosalicylate (3,6-DCSA) in Rhizorhabdus dicambivorans Ndbn-20. In the present study, a 3,6-DCSA-degradation-deficient mutant Ndbn-20m was screened. A cluster dsmR1DABCEFGR2 was lost in this mutant. The cluster consisted of nine genes, and all of which were apparently induced by 3,6-DCSA. DsmA shared 30-36% identities with the monooxygenase components of reported three-component cytochrome P450 systems, and formed a monophyletic branch in the phylogenetic tree...
December 1, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/29196123/boosting-11-oxo-%C3%AE-amyrin-and-glycyrrhetinic-acid-synthesis-in-saccharomyces-cerevisiae-via-pairing-novel-oxidation-and-reduction-system-from-legume-plants
#20
Ming Zhu, Caixia Wang, Wentao Sun, Anqi Zhou, Ying Wang, Genlin Zhang, Xiaohong Zhou, Yixin Huo, Chun Li
Glycyrrhetinic acid (GA) and its precursor, 11-oxo-β-amyrin, are typical triterpenoids found in the roots of licorice, a traditional Chinese medicinal herb that exhibits diverse functions and physiological effects. In this study, we developed a novel and highly efficient pathway for the synthesis of GA and 11-oxo-β-amyrin in Saccharomyces cerevisiae by introducing efficient cytochrome P450s (CYP450s: Uni25647 and CYP72A63) and pairing their reduction systems from legume plants through transcriptome and genome-wide screening and identification...
November 28, 2017: Metabolic Engineering
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