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Amp deaminase

Todd A Johnson, H A Jinnah, Naoyuki Kamatani
Germline mutations in cellular-energy associated genes have been shown to lead to various monogenic disorders. Notably, mitochondrial disorders often impact skeletal muscle, brain, liver, heart, and kidneys, which are the body's top energy-consuming organs. However, energy-related dysfunctions have not been widely seen as causes of common diseases, although evidence points to such a link for certain disorders. During acute energy consumption, like extreme exercise, cells increase the favorability of the adenylate kinase reaction 2-ADP -> ATP+AMP by AMP deaminase degrading AMP to IMP, which further degrades to inosine and then to purines hypoxanthine -> xanthine -> urate...
2019: Frontiers in Pharmacology
Chiara Baccolini, Claus-Peter Witte
Plants can fully catabolize purine nucleotides. A firmly established central intermediate is the purine base xanthine. In the current, widely accepted model of plant purine nucleotide catabolism, xanthine can be generated in various ways involving either inosine and hypoxanthine or guanosine and xanthosine as intermediates. In a comprehensive mutant analysis involving single and multiple mutants of urate oxidase, xanthine dehydrogenase, nucleoside hydrolases, guanosine deaminase, and hypoxanthine guanine phosphoribosyltransferase, we demonstrate that purine nucleotide catabolism in Arabidopsis thaliana mainly generates xanthosine, but not inosine and hypoxanthine, and that xanthosine is derived from guanosine deamination and a second source, likely xanthosine monophosphate (XMP) dephosphorylation...
February 20, 2019: Plant Cell
Qian Jia, Wei Xie
Adenosine deaminase is involved in adenosine degradation and salvage pathway, and plays important physiological roles in purine metabolism. Recently, a novel type of adenosine deaminase-like protein has been identified, which displays deamination activity toward N6-methyl-adenosine monophosphate but not adenosine or AMP, and was consequently named N6-methyl-AMP deaminase (MAPDA). The underlying structural basis of MAPDA recognition and catalysis is poorly understood. Here, we present the crystal structures of MAPDA from Arabidopsis thaliana in the free and in the ligand-bound forms...
February 5, 2019: Nucleic Acids Research
Shahbaz Ahmad, Riaz Mahmood
Mercury is among the most toxic heavy metals and a widespread environmental pollutant. Mercury chloride (HgCl2 ) is an inorganic compound of mercury which is easily absorbed in the gastrointestinal tract and then enters the blood where it can interact with erythrocytes. In this study, the effect of HgCl2 on human erythrocytes was studied under in vitro conditions. Erythrocytes were treated with different concentrations of HgCl2 (1-100 μM) for 1 h at 37 °C. Cell lysates were prepared and assayed for several biochemical parameters...
January 5, 2019: Environmental Science and Pollution Research International
J R Edgar, M L Wong, M Hale, C N Menezes
BACKGROUND: Pleural effusions are a common reason for presentation to healthcare facilities. Blind closed pleural biopsy can be a useful tool to diagnose their cause, especially in resource-limited settings. OBJECTIVES: To determine the aetiology, frequency and change in profile of histopathological diagnoses made at Chris Hani Baragwanath Academic Hospital (CHBAH), Johannesburg, South Africa, over the period 1 January 2001 - 31 December 2015. METHODS: Pleural biopsies performed at CHBAH and analysed by histopathologists from the National Health Laboratory Service at the hospital over the study period were retrospectively reviewed by accessing reports from two databases (DISA and TrakCare)...
December 13, 2018: South African Medical Journal
Ryota Eguchi, Soichiro Yamaguchi, Ken-Ichi Otsuguro
Purinergic signaling via ATP and adenosine produced by astrocytes is one pathway underlying neuron-glia interactions in the central nervous system (CNS). In production of purines, extracellular metabolism of released purines via ecto-enzymes is important. The expression and activities of these enzymes are altered under pathological conditions. Production of fibroblast growth factor 2 (FGF2) is increased under pathological conditions, and this has various effects on astrocytes. Here, we investigated the effects of FGF2 on purine metabolism in cultured rat spinal cord astrocytes...
December 14, 2018: Journal of Pharmacological Sciences
Barbara Kutryb-Zajac, Alicja Bulinska, Magdalena A Zabielska, Paulina Mierzejewska, Ewa M Slominska, Ryszard T Smolenski
Animal models are widely used in atherosclerosis research. The most useful, economic and valid is mouse genetic model of this pathology. Purinergic signaling is an important mechanism regulating processes involved in the vascular inflammation and atherosclerosis. The aim of this study was to measure vascular activities of nucleotide and adenosine-degrading ecto-enzymes in different strains of mice and to compare them to atherosclerotic susceptibility. The vascular extracellular nucleotide catabolism pathway was analyzed in 6-month-old male genetically unmodified mouse strains: FVB/NJ, DBA/2J, BALB/c, C57Bl/6J and mouse knock-outs on C57Bl/6J background for LDLR (LDLR-/-) and for ApoE and LDLR (ApoE-/-LDLR-/-)...
December 27, 2018: Nucleosides, Nucleotides & Nucleic Acids
Xin-Kai Zhang, Ming-Yue Nie, Jun Chen, Liu-Jing Wei, Qiang Hua
Lycopene has been broadly studied in recent decades due to its health benefits including cancer prevention, anti-atherogenic and anti-obesity effects, and modulation of the immune system. To obtain efficient synthesis of lycopene, extensive researches have been conducted in various microbial cells, including Yarrowia lipolytica, to heterologously produce lycopene using various genetic and metabolic engineering methods. In this study, the effects of copy numbers of lycopene synthesis genes, a variety of key central metabolic genes (especially AMP deaminase-encoding gene AMPD), and 5-L fermenter cultivation on lycopene production in Y...
November 15, 2018: Journal of Biotechnology
Anna Bin, Valentina Caputi, Michela Bistoletti, Monica Montopoli, Rocchina Colucci, Luca Antonioli, Sara De Martin, Ignazio Castagliuolo, Genny Orso, Cristina Giaroni, Patrizia Debetto, Maria Cecilia Giron
Adenosine is a versatile signaling molecule recognized to physiologically influence gut motor functions. Both the duration and magnitude of adenosine signaling in enteric neuromuscular function depend on its availability, which is regulated by the ecto-enzymes ecto-5'-nucleotidase (CD73), alkaline phosphatase (AP), and ecto-adenosine deaminase (ADA) and by dipyridamole-sensitive equilibrative transporters (ENTs). Our purpose was to assess the involvement of CD73, APs, ecto-ADA in the formation of AMP-derived adenosine in primary cultures of ileal myofibroblasts (IMFs)...
September 29, 2018: Purinergic Signalling
Linjie Wang, Zhe Chao, Yan Wang
The AMP deaminase 1 (AMPD1) gene plays an important role in purine nucleotide interconversion and energy metabolism. In this study, two novel single nucleotide polymorphisms (SNPs) (g.-626 G > A and g.-566 A>G) were detected in the proximal promoter region of the AMPD1 gene. The Chinese indigenous pig breeds (Meishan and Tongcheng) had higher frequencies of the G and A alleles than Western meat-type breeds (Landrace and Large White) at the g.-626 G > A and g.-566 A>G loci. The transcriptional activity of the AMPD1 promoter carrying the haplotype H1 (A-626 G-566 ) was significantly (p < 0...
November 2018: DNA and Cell Biology
M-N Theodoraki, T K Hoffmann, E K Jackson, T L Whiteside
Exosomes in plasma of head and neck squamous cell carcinoma (HNSCC) patients comprise subsets of vesicles derived from various cells. Recently, we separated CD3(+) from CD3(-) exosomes by immune capture. CD3(-) exosomes were largely tumour-derived (CD44v3+ ). Both subsets carried immunosuppressive proteins and inhibited functions of human immune cells. The role of these subsets in immune cell reprogramming by the tumour was investigated by focusing on the adenosine pathway components. Spontaneous adenosine production by CD3(+) or CD3(-) exosomes was measured by mass spectrometry, as was the production of adenosine by CD4+ CD39+ regulatory T cells (Treg ) co-incubated with these exosomes...
October 2018: Clinical and Experimental Immunology
Francesca Ronca, Antonio Raggi
Multiple muscle-specific isoforms of the Zn2+ metalloenzyme AMP deaminase (AMPD) have been identified based on their biochemical and genetic differences. Our previous observations suggested that the metal binding protein histidine-proline-rich glycoprotein (HPRG) participates in the assembly and maintenance of skeletal muscle AMP deaminase (AMPD1) by acting as a zinc chaperone. The evidence of a role of millimolar-strength phosphate in stabilizing the AMPD-HPRG complex of both AMPD1 and cardiac AMP deaminase (AMPD3) is suggestive of a physiological mutual dependence between the two subunit components with regard to the stability of the two isoforms of striated muscle AMPD...
August 23, 2018: Biomolecules
Shuai Yuan, Xiaofeng Jiang, Xinyu Zhou, Yuqing Zhang, Teng Teng, Peng Xie
Inosine, a major breakdown product of adenosine by the enzyme adenosine deaminase, binds to adenosine receptors and initiates intracellular signaling events. Adenosine and inosine have already been described as capable of modulating depression-like behavior in adult rodent model. In this study, we investigated the antidepressant-like effect of inosine, acutely administered (10 or 50 mg/kg, intraperitoneal), in postnatal day 28 male Sprague-Dawley rats. The effects of inosine were assessed using the forced swimming test and locomotor activity test...
September 26, 2018: Neuroreport
David F Wilson, Franz M Matschinsky
A model of oxidative phosphorylation and its regulation is presented that is consistent with the experimental data on metabolism in higher plants and animals. The variables that provide real time control of metabolic status are: intramitochondrial [NAD+ ]/[NADH], energy state ([ATP]/[ADP][Pi]), and local oxygen concentration ([O2 ]). ATP consumption and respiratory chain enzyme content are tissue specific (liver vs heart muscle) and the latter is modulated by chronic alterations in ATP consumption (i.e. endurance training etc)...
July 12, 2018: Journal of Applied Physiology
Naďa Špačková, Kamila Réblová
Adenosine to inosine (A⁻I) editing is the most common modification of double-stranded RNA (dsRNA). This change is mediated by adenosine deaminases acting on RNA (ADARs) enzymes with a preference of U>A>C>G for 5&prime; neighbor and G>C=A>U or G>C>U=A for 3&prime; neighbor. A⁻I editing occurs most frequently in the non-coding regions containing repetitive elements such as ALUs. It leads to disruption of RNA duplex structure, which prevents induction of innate immune response...
June 28, 2018: Genes
Debjit Das, Payel Das, Mahammed Moniruzzaman, Mousumi Poddar Sarkar, Joyita Mukherjee, Suman Bhusan Chakraborty
Current study aims to find interrelation between mitochondrial enzyme function and fatty acid profile in fish muscle and role of antioxidant agents to maintain their balance in response to metal accumulation. Fishes (Labeo rohita, Catla catla, Cirrhinus cirrhosus) were collected from two sites (Nalban Bheri and Diamond Harbour, India). Concentrations of metals (lead, cadmium, copper, nickel, zinc), enzymatic and non-enzymatic antioxidant activity (malondialdehyde, superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione S-transferase), muscle enzyme activity (acetylcholinesterase, succinate dehydrogenase, lactate dehydrogenase, Ca2+ ATPase, AMP-deaminase, lipoamide reductase, cytochrome C oxidase, aldolase) and fatty acid composition in muscle tissues were analyzed...
September 2018: Chemosphere
I M Rybakowska, B Kutryb-Zając, R Milczarek, B Łukasz, E M Slominska, R T Smolenski
Nucleotide metabolism plays a major role in a number of vital cellular processes such as energetics. This, in turn, is important in pathologies such as atherosclerosis. Three month old atherosclerotic mice with knock outs for LDLR and apolipoprotein E (ApoE) were used for the experiments. Activities of AMP-deaminase (AMPD), ecto5'-nucleotidase (e5NT), adenosine deaminase (ADA), purine nucleoside phosphorylase (PNP) were measured in heart, liver and kidney cortex and medulla by analysing conversion of substrates into products using HPLC...
2018: Nucleosides, Nucleotides & Nucleic Acids
Timothy F Cloughesy, Joseph Landolfi, Michael A Vogelbaum, Derek Ostertag, James B Elder, Stephen Bloomfield, Bob Carter, Clark C Chen, Steven N Kalkanis, Santosh Kesari, Albert Lai, Ian Y Lee, Linda M Liau, Tom Mikkelsen, Phioanh Nghiemphu, David Piccioni, William Accomando, Oscar R Diago, Daniel J Hogan, Dawn Gammon, Noriyuki Kasahara, Thian Kheoh, Douglas J Jolly, Harry E Gruber, Asha Das, Tobias Walbert
Background: Vocimagene amiretrorepvec (Toca 511) is an investigational gamma-retroviral replicating vector encoding cytosine deaminase that, when used in combination with extended-release 5-fluorocytosine (Toca FC), results preclinically in local production of 5-fluorouracil, depletion of immune-suppressive myeloid cells, and subsequent induction of antitumor immunity. Recurrent high-grade glioma (rHGG) patients have a high unmet need for effective therapies that produce durable responses lasting more than 6 months...
September 3, 2018: Neuro-oncology
Yuki Tatekoshi, Masaya Tanno, Hidemichi Kouzu, Koki Abe, Takayuki Miki, Atsushi Kuno, Toshiyuki Yano, Satoko Ishikawa, Wataru Ohwada, Tatsuya Sato, Takeshi Niinuma, Hiromu Suzuki, Tetsuji Miura
AMP deaminase (AMPD) plays a crucial role in adenine nucleotide metabolism. Recently we found that upregulated AMPD activity is associated with ATP depletion and contractile dysfunction under the condition of pressure overloading in the heart of a rat model of type 2 diabetes mellitus (T2DM), OLETF. Here we examined the mechanism of AMPD upregulation by T2DM. The protein level of 90-kDa full-length AMPD3 was increased in whole myocardial lysates by 55% in OLETF compared to those in LETO, a non-diabetic control...
June 2018: Journal of Molecular and Cellular Cardiology
Yu Wang, Ye Liu, Jiao Liu, Yanmei Guo, Liwen Fan, Xiaomeng Ni, Xiaomei Zheng, Meng Wang, Ping Zheng, Jibin Sun, Yanhe Ma
CRISPR/Cas9 or Cpf1-introduced double strand break dramatically decreases bacterial cell survival rate, which hampers multiplex genome editing in bacteria. In addition, the requirement of a foreign DNA template for each target locus is labor demanding and may encounter more GMO related regulatory hurdle in industrial applications. Herein, we developed a multiplex automated Corynebacterium glutamicum base editing method (MACBETH) using CRISPR/Cas9 and activation-induced cytidine deaminase (AID), without foreign DNA templates, achieving single-, double-, and triple-locus editing with efficiencies up to 100%, 87...
May 2018: Metabolic Engineering
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