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https://www.readbyqxmd.com/read/28222405/thyroid-hormones-a-potential-ally-to-ldl-cholesterol-lowering-agents
#1
REVIEW
Leonidas N Duntas, Gabriela Brenta
L-thyroxine (LT4) treatment of hypothyroidism, particularly in patients with thyroid- stimulating hormone (TSH) >10mU/L, results in improved lipid profile, as LT4 stimulates low-density lipoprotein cholesterol (LDL-C) degradation and the conversion of cholesterol in bile acids by inducing LDL-receptor and 7 alpha hydroxylase expression, respectively. Statins decrease total cholesterol (TC) and LDL-C mainly by suppressing 3-hydroxy-3-methylglutaryl coenzyme A activity. Therefore, the addition of statins to LT4 treatment, following the reversal of hypothyroidism, acts synergistically and forms a powerful treatment modality in patients with this condition whose serum lipids have not achieved the target...
October 2016: Hormones: International Journal of Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28221362/disrupted-iron-regulation-in-the-brain-and-periphery-in-cocaine-addiction
#2
K D Ersche, J Acosta-Cabronero, P S Jones, H Ziauddeen, R P L van Swelm, C M M Laarakkers, R Raha-Chowdhury, G B Williams
Stimulant drugs acutely increase dopamine neurotransmission in the brain, and chronic use leads to neuroadaptive changes in the mesolimbic dopamine system and morphological changes in basal ganglia structures. Little is known about the mechanisms underlying these changes but preclinical evidence suggests that iron, a coenzyme in dopamine synthesis and storage, may be a candidate mediator. Iron is present in high concentrations in the basal ganglia and stimulant drugs may interfere with iron homeostasis. We hypothesised that morphological brain changes in cocaine addiction relate to abnormal iron regulation in the brain and periphery...
February 21, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28220528/enzymatic-characterization-and-functional-implication-of-two-structurally-different-isocitrate-dehydrogenases-from-xylella-fastidiosa
#3
Peipei Lv, Wanggang Tang, Peng Wang, Zhengyu Cao, Guoping Zhu
Isocitrate dehydrogenase (IDH) is a key enzyme at the critical junction between the tricarboxylic acid cycle and the glyoxylate cycle. Most bacteria have only one IDH, while a few of bacteria contain two IDH isozymes. The coexistence of two different type IDHs in one organism was little known. Xylella fastidiosa is a nutritionally fastidious plant pathogen that contains two structurally different IDHs, an NAD(+) -dependent homodimeric IDH (diXfIDH) and an NADP(+) -dependent monomeric IDH (monoXfIDH). Kinetic characterization showed that diXfIDH displayed 206-fold preferences for NAD(+) over NADP(+) , while monoXfIDH showed 13800-fold preferences for NADP(+) over NAD(+) ...
February 21, 2017: Biotechnology and Applied Biochemistry
https://www.readbyqxmd.com/read/28220152/lack-of-mycothiol-and-ergothioneine-induces-different-protective-mechanisms-in-mycobacterium-smegmatis
#4
Arishma Rajkarnikar Singh, Andrew Strankman, Ruzan Orkusyan, Endang Purwantini, Mamta Rawat
Mycobacterium smegmatis contains the low molecular weight thiols, mycothiol (MSH) and ergothioneine (ESH). Examination of transposon mutants disrupted in mshC and egtA, involved in the biosynthesis of MSH and ESH respectively, demonstrated that both mutants were sensitive to oxidative, alkylating, and metal stress. However, the mshC mutant exhibited significantly more protein carbonylation and lipid peroxidation than wildtype, while the egtA mutant had less protein and lipid damage than wildtype. We further show that Ohr, KatN, and AhpC, involved in protection against oxidative stress, are upregulated in the egtA mutant...
December 2016: Biochemistry and Biophysics Reports
https://www.readbyqxmd.com/read/28219711/oxidative-stress-inactivates-ecto-5-nucleotidase-by-inhibiting-protein-kinase-c-in-rat-hearts-in-vivo
#5
Toshio Obata, Michiko Nakashima
Examined in the present study, allopurinol are xanthine oxidase inhibitors for use in rat hearts in vivo dialysis technology and ventricular myocardial intersitial adenosine production can increase. The microdialysis probe was implanted in the left ventricular myocardium of anesthetized rat hearts and the tissue in the vicinity of the dialysis was perfused with Tyrode's solution containing adenosine 5'-monophosphate (AMP) through the dialysis probe at a rate of 1.0ml/min to assess the activity of ecto-5'-nucleotidase...
February 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28219701/amelioratory-effect-of-coenzyme-q10-on-potential-human-carcinogen-microcystin-lr-induced-toxicity-in-mice
#6
Yaqoob Lone, Mangla Bhide, Raj Kumar Koiri
Microcystins are a group of cyclic heptapeptide toxins produced by cyanobacteria. More than 100 microcystin analogues have been detected, among which microcystin-LR is the most abundant and toxic variant. Present study was designed to reveal whether potential human carcinogen microcystin-LR could imbalance the glycolytic-oxidative-nitrosative status of heart, kidney and spleen of mice and also to explore the amelioratory effect of coenzyme Q10 on microcystin-LR induced toxicity. Microcystin-LR was administered at a dose of 10 μg/kg bw/day, ip for 14 days in male mice...
February 17, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/28214879/thiamine-deprivation-produces-a-liver-atp-deficit-and-metabolic-and-genomic-effects-in-mice-findings-are-parallel-to-those-of-biotin-deficiency-and-have-implications-for-energy-disorders
#7
Alain de J Hernandez-Vazquez, Josue Andres Garcia-Sanchez, Elizabeth Moreno-Arriola, Ana Salvador-Adriano, Daniel Ortega-Cuellar, Antonio Velazquez-Arellano
Thiamine is one of several essential cofactors for ATP generation. Its deficiency, like in beriberi and in the Wernicke-Korsakoff syndrome, has been studied for many decades. However, its mechanism of action is still not completely understood at the cellular and molecular levels. Since it acts as a coenzyme for dehydrogenases of pyruvate, branched-chain keto acids, and ketoglutarate, its nutritional privation is partly a phenocopy of inborn errors of metabolism, among them maple syrup urine disease. In the present paper, we report metabolic and genomic findings in mice deprived of thiamine...
February 18, 2017: Journal of Nutrigenetics and Nutrigenomics
https://www.readbyqxmd.com/read/28209347/high-resolution-mass-spectrometry-based-method-applicable-for-a-wide-range-of-3-hydroxy-3-methyl-glutaryl-coenzyme-a-reductase-inhibitors-in-blood-serum-including-intermediates-and-products-of-the-cholesterol-biosynthetic-pathway
#8
Vít Kosek, Milena Stránská, Marie Fenclová, Tomáš Ruml, Libor Vítek, Jana Hajšlová
Statins belong to the major class of hypolipidemic drugs. They act as competitive inhibitors of 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme in the cholesterol biosynthetic pathway. This inhibition not only leads to the depletion of cholesterol and its fatty acid esters, but also to the depletion of the intermediates of this metabolic pathway (mainly pyrophosphates), which can play an important role in tumor proliferation. The aim of the current study was to establish a versatile multi-analyte method capable of quantitative determination of various currently-used statins, together with free cholesterol (FC), cholesterol esters (CEs), and some key intermediates of the mevalonate pathway occurring in human serum...
January 31, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28208756/homocysteine-editing-thioester-chemistry-coenzyme-a-and-the-origin-of-coded-peptide-synthesis-%C3%A2
#9
REVIEW
Hieronim Jakubowski
Aminoacyl-tRNA synthetases (AARSs) have evolved "quality control" mechanisms which prevent tRNA aminoacylation with non-protein amino acids, such as homocysteine, homoserine, and ornithine, and thus their access to the Genetic Code. Of the ten AARSs that possess editing function, five edit homocysteine: Class I MetRS, ValRS, IleRS, LeuRS, and Class II LysRS. Studies of their editing function reveal that catalytic modules of these AARSs have a thiol-binding site that confers the ability to catalyze the aminoacylation of coenzyme A, pantetheine, and other thiols...
February 9, 2017: Life
https://www.readbyqxmd.com/read/28207435/statin-associated-immune-mediated-myopathy-biology-and-clinical-implications
#10
Lisa Christopher-Stine, Pari Basharat
PURPOSE OF REVIEW: In the last 6 years, our understanding of statin-associated myopathy expanded to include not only a toxic myopathy with limited and reversible side-effects but also an autoimmune variety in which statins likely induce an autoimmune myopathy that is both associated with a specific autoantibody and responsive to immunosuppression and immune modulation. This review widens the reader's understanding of statin myopathy to include an autoimmune process. RECENT FINDINGS: Statin-associated immune-mediated myopathy provides an example of an environmental trigger (statins) directly implicated in an autoimmune disease associated with a genetic predisposition as well as potential risk factors including concomitant diseases and specific statins...
February 14, 2017: Current Opinion in Lipidology
https://www.readbyqxmd.com/read/28205597/the-influence-of-accd5-on-accd6-carboxyltransferase-essentiality-in-pathogenic-and-non-pathogenic-mycobacterium
#11
Jakub Pawelczyk, Albertus Viljoen, Laurent Kremer, Jaroslaw Dziadek
Malonyl-coenzyme A (CoA) is a crucial extender unit for the synthesis of mycolic and other fatty acids in mycobacteria, generated in a reaction catalyzed by acetyl-CoA carboxylase. We previously reported on the essentiality of accD6Mtb encoding the functional acetyl-CoA carboxylase subunit in Mycobacterium tuberculosis. Strikingly, the homologous gene in the fast-growing, non-pathogenic Mycobacterium smegmatis - (accD6Msm) appeared to be dispensable, and its deletion did not influence the cell lipid content...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203522/mass-spectral-determination-of-phosphopantetheinylation-specificity-for-carrier-proteins-in-mycobacterium-tuberculosis
#12
James Jung, Ghader Bashiri, Jodie M Johnston, Edward N Baker
Phosphopantetheinyl transferases (PPTases) are key elements in the modular syntheses performed by multienzyme systems such as polyketide synthases. PPTases transfer phosphopantetheine derivatives from Coenzyme A to carrier proteins (CPs), thus orchestrating substrate supply. We describe an efficient mass spectrometry-based protocol for determining CP specificity for a particular PPTase in organisms possessing several candidate PPTases. We show that the CPs MbtL and PpsC, both involved in synthesis of essential metabolites in Mycobacterium tuberculosis, are exclusively activated by the type 2 PPTase PptT and not the type 1 AcpS...
December 2016: FEBS Open Bio
https://www.readbyqxmd.com/read/28201987/an-integrative-metabolomics-and-transcriptomics-study-to-identify-metabolic-alterations-in-aged-skin-of-humans-in-vivo
#13
Andreas Kuehne, Janosch Hildebrand, Joern Soehle, Horst Wenck, Lara Terstegen, Stefan Gallinat, Anja Knott, Marc Winnefeld, Nicola Zamboni
BACKGROUND: Aging human skin undergoes significant morphological and functional changes such as wrinkle formation, reduced wound healing capacity, and altered epidermal barrier function. Besides known age-related alterations like DNA-methylation changes, metabolic adaptations have been recently linked to impaired skin function in elder humans. Understanding of these metabolic adaptations in aged skin is of special interest to devise topical treatments that potentially reverse or alleviate age-dependent skin deterioration and the occurrence of skin disorders...
February 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28196894/extending-enzyme-molecular-recognition-with-an-expanded-amino-acid-alphabet
#14
Claire L Windle, Katie J Simmons, James R Ault, Chi H Trinh, Adam Nelson, Arwen R Pearson, Alan Berry
Natural enzymes are constructed from the 20 proteogenic amino acids, which may then require posttranslational modification or the recruitment of coenzymes or metal ions to achieve catalytic function. Here, we demonstrate that expansion of the alphabet of amino acids can also enable the properties of enzymes to be extended. A chemical mutagenesis strategy allowed a wide range of noncanonical amino acids to be systematically incorporated throughout an active site to alter enzymic substrate specificity. Specifically, 13 different noncanonical side chains were incorporated at 12 different positions within the active site of N-acetylneuraminic acid lyase (NAL), and the resulting chemically modified enzymes were screened for activity with a range of aldehyde substrates...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28196160/clinical-efficacy-of-subgingivally-delivered-1-2-mg-simvastatin-in-the-treatment-of-patients-with-aggressive-periodontitis-a-randomized-controlled-clinical-trial
#15
Priyanka N, A Abhilash, Shahab Saquib, Nikhil Malgaonkar, Nitin Kudyar, Aashima Gupta, Nitish Kalra, A R Pradeep
Simvastatin (SMV) is a specific competitive inhibitor of 3-hydroxy-2-methylglutaryl coenzyme A reductase that promotes bone formation. The present clinical trial was designed to investigate the effectiveness of 1.2 mg SMV as a local drug delivery system and as an adjunct to scaling and root planing (SRP) in the treatment of aggressive periodontitis (AgP). A total of 68 intrabony defects from 24 patients with AgP were treated either with 1.2 mg SMV gel or placebo gel. The subjects were randomly assigned to SRP + placebo (group 1; n = 12) or SRP + SMV (group 2; n = 12)...
March 2017: International Journal of Periodontics & Restorative Dentistry
https://www.readbyqxmd.com/read/28191552/a-common-mechanism-for-coenzyme-cobalamin-dependent-reductive-dehalogenases
#16
Linus O Johannissen, David Leys, Sam Hay
Distinct mechanisms have been proposed for the biological dehalogenation catalyzed by cobalamin-dependent enzymes, with two recent crystallographic studies suggesting different mechanisms based on the observed interaction between the organohalide substrate and cobalamin. In one case, involving an aromatic dibromide substrate in NpRdhA, a novel Co(II)-Br interaction was observed using EPR, suggesting a mechanism involving a [CoXR] adduct. However, in the case of trichloroethylene in PceA, a significantly longer Co-Cl distance was observed in X-ray crystal structures, suggesting a dissociative electron transfer mechanism...
February 13, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28190603/neuroprotective-effects-of-a-novel-antioxidant-mixture-twendee-x-in-mouse-stroke-model
#17
Momoko Kusaki, Yasuyuki Ohta, Haruhiko Inufusa, Toru Yamashita, Ryuta Morihara, Yumiko Nakano, Xia Liu, Jingwei Shang, Feng Tian, Yusuke Fukui, Kota Sato, Mami Takemoto, Nozomi Hishikawa, Koji Abe
BACKGROUND: Oxidative stress and inflammation are important aggravating factors in acute ischemic stroke. METHODS: In the present study, the neuroprotective effects of a novel antioxidant mixture Twendee X containing multiple antioxidative ingredients, such as coenzyme Q10, ascorbic acid, and cystine, were evaluated. After the pretreatment of a vehicle or Twendee X (20 mg/kg/d) for 14 days, mice were subjected to transient middle cerebral artery occlusion for 60 minutes and further treated with vehicle or Twendee X for 1 or 5 days...
February 9, 2017: Journal of Stroke and Cerebrovascular Diseases: the Official Journal of National Stroke Association
https://www.readbyqxmd.com/read/28189105/determination-of-methylmalonyl-coenzyme-a-by-ultra-high-performance-liquid-chromatography-tandem-mass-spectrometry-for-measuring-propionyl-coenzyme-a-carboxylase-activity-in-patients-with-propionic-acidemia
#18
Kana Gotoh, Yoko Nakajima, Go Tajima, Yoriko Watanabe, Yuji Hotta, Tomoya Kataoka, Yoshihiro Kawade, Naruji Sugiyama, Tetsuya Ito, Kazunori Kimura, Yasuhiro Maeda
Propionic acidemia (PA) is an inherited metabolic disease caused by low activity of propionyl coenzyme A (CoA) carboxylase (PCC), which metabolizes propionyl-CoA into methylmalonyl-CoA. Although many patients with PA have been identified by tandem mass spectrometry since the test was first included in neonatal mass screening in the 1990s, the disease severity varies. Thus, determining the specific level of PCC activity is considered to be helpful to grasp the severity of PA. We developed a new PCC assay method by the determination of methylmalonyl-CoA, which is formed by an enzyme reaction using peripheral lymphocytes, based on ultra high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS)...
February 6, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28188954/comparative-glandular-trichome-transcriptome-based-gene-characterization-reveals-reasons-for-differential-menthol-biosynthesis-in-mentha-species
#19
Md Qussen Akhtar, Nida Qamar, Pallavi Yadav, Pallavi Kulkarni, Ajay Kumar, Ajit Kumar Shasany
The genes involved in menthol biosynthesis are reported earlier in Mentha × piperita. But the information on these genes is not available in Mentha arvensis. To bridge the gap in knowledge on differential biosynthesis of monoterpenes leading to compositional variation in the essential oil of these species, a comparative transcriptome analysis of the glandular trichome was carried out. In addition to the MVA and MEP pathway genes, about 210 and 196 different terpene synthases (TPS) transcripts were identified from annotation in M...
February 11, 2017: Physiologia Plantarum
https://www.readbyqxmd.com/read/28188804/metabolite-profiling-of-infection-associated-metabolic-markers-of-onchocerciasis
#20
Sasisekhar Bennuru, Sara Lustigman, David Abraham, Thomas B Nutman
The global efforts for onchocerciasis elimination may require additional tools (safe micro and macrofilaricidal drugs, vaccines and biomarkers) as elimination efforts move toward the "end game". Efforts toward the identification of suitable biomarkers have focused on specific protein(s) and/or nucleic acids, but metabolites present an alternative option as they have limited half-lives and are the result of combinatorial effects. In comparison to previously used methodology of LC-MS for metabolomic approaches, we used a non-targeted capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS) to analyze the serum metabolic profiles of Ov-infected and -uninfected individuals (n=20)...
February 8, 2017: Molecular and Biochemical Parasitology
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