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https://www.readbyqxmd.com/read/28650504/experimental-and-theoretical-studies-on-fluvastatin-primary-photoproduct-formation
#1
Dorota Jarmużek, Tomasz Pedzinski, Marcin Hoffmann, Tomasz Siodła, Kinga Salus, Donata Pluskota-Karwatka
Fluvastatin (FLV) belongs to the group of compounds referred to as statins, also known as 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors. Statins act as cholesterol-lowering agents and are among the most frequently prescribed drugs. They upregulate low-density lipoprotein receptors in the liver by binding to the active site of HMG-CoA reductase, which is the key enzyme in cholesterol biosynthesis. Statins have been detected as contaminants in natural waters and are susceptible to degradation upon exposure to light...
June 26, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28647025/olumacostat-glasaretil-a-promising-topical-sebum-suppressing-agent-that-affects-all-major-pathogenic-factors-of-acne-vulgaris
#2
Bodo C Melnik
Hunt et al. show that olumacostat glasaretil, an inhibitor of acetyl coenzyme A carboxylase, reduces saturated and monounsaturated fatty acyl chains in sebaceous lipids. Topical olumacostat glasaretil application decreases hamster ear sebaceous gland size and shows efficacy in treating patients with acne vulgaris. Olumacostat glasaretil-mediated sebum suppression may reduce Propionibacterium acnes growth and biofilm formation, comedogenesis, and inflammation.
July 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28646149/crucial-role-of-4-deoxy-l-erythro-5-hexoseulose-uronate-reductase-for-alginate-utilization-revealed-by-adaptive-evolution-in-engineered-saccharomyces-cerevisiae
#3
Fumiya Matsuoka, Makoto Hirayama, Takayuki Kashihara, Hideki Tanaka, Wataru Hashimoto, Kousaku Murata, Shigeyuki Kawai
In brown macroalgae, alginate and D-mannitol are promising carbohydrates for biorefinery. Saccharomyces cerevisiae is widely used as a microbial cell factory, but this budding yeast is unable to utilize either alginate or D-mannitol. Alginate can be depolymerized by both endo-type and exo-type alginate lyases, yielding a monouronate, 4-deoxy-L-erythro-5-hexoseulose uronate (DEH), a key intermediate in the metabolism of alginate. Here, we constructed engineered two S. cerevisiae strains that are able to utilize both DEH and D-mannitol on two different strain backgrounds, and we also improved their aerobic growth in a DEH liquid medium through adaptive evolution...
June 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28643190/mitochondrial-biogenesis-and-neural-differentiation-of-human-ipsc-is-modulated-by-idebenone-in-a-developmental-stage-dependent-manner
#4
J Augustyniak, J Lenart, M Zychowicz, P P Stepien, L Buzanska
Idebenone, the synthetic analog of coenzyme Q10 can improve electron transport in mitochondria. Therefore, it is used in the treatment of Alzheimer's disease and other cognitive impairments. However, the mechanism of its action on neurodevelopment is still to be elucidated. Here we demonstrate that the cellular response of human induced pluripotent stem cells (hiPSC) to idebenone depends on the stage of neural differentiation. When: neural stem cells (NSC), early neural progenitors (eNP) and advanced neural progenitors (NP) have been studied a significant stimulation of mitochondrial biogenesis was observed only at the eNP stage of development...
June 22, 2017: Biogerontology
https://www.readbyqxmd.com/read/28643139/cysteamine-revisited-repair-of-arginine-to-cysteine-mutations
#5
REVIEW
L Gallego-Villar, L Hannibal, J Häberle, B Thöny, T Ben-Omran, G K Nasrallah, Al-N Dewik, W D Kruger, H J Blom
Cysteamine is a small aminothiol endogenously derived from coenzyme A degradation. For some decades, synthetic cysteamine has been employed for the treatment of cystinosis, and new uses of the drug continue to emerge. In this review, we discuss the role of cysteamine in cellular and extracellular homeostasis and focus on the potential use of aminothiols to reconstitute the function of proteins harboring arginine (Arg) to cysteine (Cys) mutations, via repair of the Cys residue into a moiety that introduces an amino group, as seen in basic amino acid residues Lys and Arg...
June 22, 2017: Journal of Inherited Metabolic Disease
https://www.readbyqxmd.com/read/28642201/combination-of-coenzyme-q10-loaded-liposomes-with-ultrasound-targeted-microbubbles-destruction-utmd-for-early-theranostics-of-diabetic-nephropathy
#6
Ting Yue, He-Lin Xu, Pian-Pian Chen, Lei Zheng, Qun Huang, Wen-Shuang Sheng, Yuan-Di Zhuang, Li-Zhuo Jiao, Ting-Ting Chi, De-Li ZhuGe, Jin-Jin Liu, Ying-Zheng Zhao, Li Lan
Diabetic nephropathy (DN) is one of the most common and lethal microvascular complications of diabetes. This study aimed to explore whether coenzymeQ10 (CoQ10) as an antioxidant combined with ultrasound-targeted microbubble destruction (UTMD) could reverse the progress of early diabetic nephropathy (DN). CoQ10 has great potential to treat early DN. However, the clinical application of CoQ10 has been limited because of its low aqueous solubility and non-specific distribution. Therefore, CoQ10-loaded liposomes (CoQ10-lip) were prepared and combined with ultrasound microbubbles for the early theranostics of DN...
June 19, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28640600/horse-liver-alcohol-dehydrogenase-zinc-coordination-and-catalysis
#7
Bryce V Plapp, Baskar Raj Savarimuthu, Daniel J Ferraro, Jon K Rubach, Eric N Brown, Subramanian Ramaswamy
: During catalysis by liver alcohol dehydrogenase (ADH), a water bound to the catalytic zinc is replaced by the oxygen of the substrates. The mechanism may involve a pentacoordinated zinc or a double displacement reaction with participation by a nearby glutamate residue, as suggested by studies of human ADH3, yeast ADH1 and some other tetrameric ADHs. Zinc coordination and participation of water in the enzyme mechanism were investigated by X-ray crystallography. Apoenzyme and its complex with adenosine 5'-diphosphoribose have an open protein conformation with the catalytic zinc in one position, tetracoordinated by Cys-46, His-67, Cys-174 and a water molecule...
June 22, 2017: Biochemistry
https://www.readbyqxmd.com/read/28637419/pharmacological-inhibitors-of-nad-biosynthesis-as-potential-anticancer-agents
#8
Stephanie Lucas, Claire Soave, Gazal Nabil, Zainab Ahmed, Guohua Chen, Hossny El-Banna, Q Ping Dou, Jian Wang
BACKGROUND: Alteration of cellular metabolism is a hallmark of cancer, which underlies exciting opportunities to develop effective, anti-cancer therapeutics by targeting through inhibition of cancer metabolism. Nicotinamide adenine dinucleotide (NAD+), an essential coenzyme of energy metabolism and a signaling molecule linking cellular energy status to a spectrum of molecular regulation, has been shown to be in high demand in a variety of cancer cells. Depletion of NAD+ by inhibition of its key biosynthetic enzymes has become an attractive strategy to target cancer...
June 19, 2017: Recent Patents on Anti-cancer Drug Discovery
https://www.readbyqxmd.com/read/28636641/development-of-a-range-of-fluorescent-reagentless-biosensors-for-atp-based-on-malonyl-coenzyme-a-synthetase
#9
Renée Vancraenenbroeck, Simone Kunzelmann, Martin R Webb
The range of ATP concentrations that can be measured with a fluorescent reagentless biosensor for ATP has been increased by modulating its affinity for this analyte. The ATP biosensor is an adduct of two tetramethylrhodamines with MatB from Rhodopseudomonas palustris. Mutations were introduced into the binding site to modify ATP binding affinity, while aiming to maintain the concomitant fluorescence signal. Using this signal, the effect of mutations in different parts of the binding site was measured. This mutational analysis revealed three variants in particular, each with a single mutation in the phosphate-binding loop, which had potentially beneficial changes in ATP binding properties but preserving a fluorescence change of ~3-fold on ATP binding...
2017: PloS One
https://www.readbyqxmd.com/read/28635632/glucose-and-lipid-dysmetabolism-in-a-rat-model-of-prediabetes-induced-by-a-high-sucrose-diet
#10
Ana Burgeiro, Manuela G Cerqueira, Bárbara M Varela-Rodríguez, Sara Nunes, Paula Neto, Frederico C Pereira, Flávio Reis, Eugénia Carvalho
Glucotoxicity and lipotoxicity are key features of type 2 diabetes mellitus, but their molecular nature during the early stages of the disease remains to be elucidated. We aimed to characterize glucose and lipid metabolism in insulin-target organs (liver, skeletal muscle, and white adipose tissue) in a rat model treated with a high-sucrose (HSu) diet. Two groups of 16-week-old male Wistar rats underwent a 9-week protocol: HSu diet (n = 10)-received 35% of sucrose in drinking water; Control (n = 12)-received vehicle (water)...
June 21, 2017: Nutrients
https://www.readbyqxmd.com/read/28632266/proteomic-analysis-reveals-xuesaitong-injection-attenuates-myocardial-ischemia-reperfusion-injury-by-elevating-pyruvate-dehydrogenase-mediated-aerobic-metabolism
#11
Xiaoping Zhao, Feng Zhang, Yi Wang
Xuesaitong injection (XST), which mainly consists of Panax notoginseng saponins, has been widely used for treating cardio-cerebral vascular diseases. However, the underlying mechanisms of XST associated with its cardioprotective effects are still unclear. To identify the potential target proteins of XST, two-dimensional gel electrophoresis (2-DE)-based proteomics was utilized to analyze the protein profile of myocardium in rats with myocardial ischemia/reperfusion (I/R) injury. The differentially expressed proteins were identified by matrix assisted laser desorption/ionization time-of-flight mass spectrometry...
June 20, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28629864/structure-function-relationships-in-human-d-aspartate-oxidase-characterisation-of-variants-corresponding-to-known-single-nucleotide-polymorphisms
#12
Masumi Katane, Ryo Kanazawa, Risa Kobayashi, Megumi Oishi, Kazuki Nakayama, Yasuaki Saitoh, Tetsuya Miyamoto, Masae Sekine, Hiroshi Homma
D-Aspartate oxidase (DDO) is a degradative enzyme that is stereospecific for the acidic amino acid D-aspartate, an endogenous agonist of the N-methyl-D-aspartate (NMDA) receptor. Dysregulation of NMDA receptor-mediated neurotransmission has been implicated in the onset of various neuropsychiatric disorders including schizophrenia and in chronic pain. Thus, appropriate regulation of the amount of D-aspartate is believed to be important for maintaining proper neural activity in the nervous system. Herein, the effects of the non-synonymous single nucleotide polymorphisms (SNPs) R216Q and S308N on several properties of human DDO were examined...
June 16, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28626134/synthesis-and-detection-by-hplc-of-3-oxohexadecanoyl-coa-for-the-study-of-peroxisomal-bifunctional-proteins
#13
Shirou Tsuchida, Ayumu Tenma, Naoya Hamaue, Tsuyoshi Murai, Teruki Yoshimura, Takashi Aoki, Takao Kurosawa
3-oxohexadecanoyl-CoA was synthesized for the study of D-bifunctional protein (EC 4. 2. 1. 107, EC 4. 2. 1. 119, EC 1. 1. 1. n12) and L-bifunctional protein (EC 4. 2. 1. 17, EC 5. 3. 3. 8, EC 1. 1. 1. 35). First, tetradecanal was subjected to the Reformatsky reaction with ethyl bromoacetate, and the product was then converted into ethyl 3-oxohexadecanoate. After acetalization of the 3-oxo ester with ethylene glycol, 3,3-ethlenedioxyhexadecanoic acid was obtained by alkaline hydrolysis. The acid was condensed with coenzyme A (CoA) by the mixed anhydride method, and the resulting CoA ester was deprotected with 4 M HCl to obtain 3-oxohexadecanoyl-CoA...
June 13, 2017: Journal of Oleo Science
https://www.readbyqxmd.com/read/28625978/the-alkylating-chemotherapeutic-temozolomide-induces-metabolic-stress-in-idh1-mutant-cancers-and-potentiates-nad-depletion-mediated-cytotoxicity
#14
Kensuke Tateishi, Fumi Higuchi, Julie Miller, Mara V A Koerner, Nina Lelic, Ganesh M Shankar, Shota Tanaka, David E Fisher, Tracy Batchelor, A John Iafrate, Hiroaki Wakimoto, Andrew S Chi, Daniel P Cahill
IDH1-mutant gliomas are dependent upon the canonical coenzyme nicotinamide adenine dinucleotide (NAD+) for survival. It is known that Poly(ADP-ribose) polymerase (PARP) activation consumes NAD+ during base excision repair (BER) of chemotherapy-induced DNA damage. We therefore hypothesized that a strategy combining NAD+ biosynthesis inhibitors with the alkylating chemotherapeutic agent temozolomide (TMZ) could potentiate NAD+ depletion-mediated cytotoxicity in mutant IDH1 cancer cells. To investigate the impact of TMZ on NAD+ metabolism, patient-derived xenografts and engineered mutant IDH1-expressing cell lines were exposed to TMZ, in vitro and in vivo, both alone and in combination with nicotinamide phosphoribosyltransferase (NAMPT) inhibitors, which block NAD+ biosynthesis...
June 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28625765/flavin-dependent-epitranscriptomic-world
#15
REVIEW
Lombard Murielle, Hamdane Djemel
RNAs molecules fulfill key roles in the expression and regulation of the genetic information stored within the DNA chromosomes. In addition to the four canonical bases, U, C, A and G, RNAs harbor various chemically modified derivatives which are generated post-transcriptionally by specific enzymes acting directly at the polymer level. More than one hundred naturally occurring modified nucleosides have been identified to date, the largest number of which is found in tRNAs and rRNA. This remarkable biochemical process produces widely diversified RNAs further expanding the functional repertoires of these nucleic acids...
June 15, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28624287/variants-in-the-3-untranslated-region-of-the-ovine-acetyl-coenzyme-a-acyltransferase-2-gene-are-associated-with-dairy-traits-and-exhibit-differential-allelic-expression
#16
D Miltiadou, A L Hager-Theodorides, S Symeou, C Constantinou, A Psifidi, G Banos, O Tzamaloukas
The acetyl-CoA acyltransferase 2 (ACAA2) gene encodes an enzyme of the thiolase family that is involved in mitochondrial fatty acid elongation and degradation by catalyzing the last step of the respective β-oxidation pathway. The increased energy needs for gluconeogenesis and triglyceride synthesis during lactation are met primarily by increased fatty acid oxidation. Therefore, the ACAA2 enzyme plays an important role in the supply of energy and carbon substrates for lactation and may thus affect milk production traits...
June 14, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28623919/effects-of-karela-bitter-melon-momordica-charantia-on-genes-of-lipids-and-carbohydrates-metabolism-in-experimental-hypercholesterolemia-biochemical-molecular-and-histopathological-study
#17
Dalia Yossri Saad, Mohamed Mohamed Soliman, Ahmed A Baiomy, Magdy Hassan Yassin, Hanan Basiouni El-Sawy
BACKGROUND: Hypercholesterolemia is a serious diseases associated with type-2 diabetes, atherosclerosis, cardiovascular disorders and liver diseases. Humans seek for safe herbal medication such as karela (Momordica charantia/bitter melon) to treat such disorders to avoid side effect of pharmacotherapies widely used. METHODS: Forty male Wistar rats were divided into four equal groups; control group with free access to food and water, cholesterol administered group (40 mg/kg BW orally); karela administered group (5 g /kg BW orally) and mixture of cholesterol and karela...
June 17, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28621732/lipid-accumulation-in-hepg2-cells-is-attenuated-by-strawberry-extract-through-ampk-activation
#18
Tamara Y Forbes-Hernández, Francesca Giampieri, Massimiliano Gasparrini, Sadia Afrin, Luca Mazzoni, Mario D Cordero, Bruno Mezzetti, José L Quiles, Maurizio Battino
Regulation of lipid metabolism is essential for treatment and prevention of several chronic diseases such as obesity, diabetes, and cardiovascular diseases, which are responsible for most deaths worldwide. It has been demonstrated that the AMP-activated protein kinase (AMPK) has a direct impact on lipid metabolism by modulating several downstream-signaling components. The main objective of the present work was to evaluate the in vitro effect of a methanolic strawberry extract on AMPK and its possible repercussion on lipid metabolism in human hepatocellular carcinoma cells (HepG2)...
June 16, 2017: Nutrients
https://www.readbyqxmd.com/read/28620248/relative-gene-expression-of-fatty-acid-synthesis-genes-at-60-days-postpartum-in-bovine-mammary-epithelial-cells-of-surti-and-jafarabadi-buffaloes
#19
Mamta Janmeda, Vishnu Kharadi, Gaurav Pandya, Balkrishna Brahmkshtri, Umed Ramani, Kuldeep Tyagi
AIM: Aim of the study was to study the relative gene expression of genes associated with fatty acid synthesis at 60 days postpartum (pp) in bovine mammary epithelial cells (MECs) of Surti and Jafarabadi buffaloes. MATERIALS AND METHODS: A total of 10 healthy Surti and Jafarabadi buffaloes of each breed were selected at random from Livestock Research Station, Navsari and Cattle Breeding Farm, Junagadh, Gujarat, respectively, for this study. Milk sample was collected from each selected buffalo at day 60 pp from these two breeds to study relative gene expression of major milk fat genes using non-invasive approach of obtaining primary bovine MECs (pBMEC) from milk samples...
May 2017: Veterinary World
https://www.readbyqxmd.com/read/28620026/learning-to-read-and-write-in-evolution-from-static-pseudoenzymes-and-pseudosignalers-to-dynamic-gear-shifters
#20
REVIEW
Abulikemu Abudukelimu, Thierry D G A Mondeel, Matteo Barberis, Hans V Westerhoff
We present a systems biology view on pseudoenzymes that acknowledges that genes are not selfish: the genome is. With network function as the selectable unit, there has been an evolutionary bonus for recombination of functions of and within proteins. Many proteins house a functionality by which they 'read' the cell's state, and one by which they 'write' and thereby change that state. Should the writer domain lose its cognate function, a 'pseudoenzyme' or 'pseudosignaler' arises. GlnK involved in Escherichia coli ammonia assimilation may well be a pseudosignaler, associating 'reading' the nitrogen state of the cell to 'writing' the ammonium uptake activity...
June 15, 2017: Biochemical Society Transactions
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