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Hyun Bong Park, Corey E Perez, Karl W Barber, Jesse Rinehart, Jason M Crawford
Nonribosomal peptides represent a large class of metabolites with pharmaceutical relevance. Pteridines, such as pterins, folates, and flavins, are heterocyclic metabolites that often serve as redox-active cofactors. The biosynthetic machineries for construction of these distinct classes of small molecules operate independently in the cell. Here, we discovered an unprecedented nonribosomal peptide synthetase-like-pteridine synthase hybrid biosynthetic gene cluster in Photorhabdus luminescens using genome synteny analysis...
March 15, 2017: ELife
Leena Liljedahl, Jenny Norlin, James N McGuire, Peter James
Diabetes mellitus (DM) is a worldwide disease that affects 9% of the adult world population and type 2 DM accounts for 90% of those. A common consequence of DM is kidney complications, which could lead to kidney failure. We studied the potential effects of treatment with insulin and the glucagon-like peptide 1 receptor (GLP-1R) agonist liraglutide on the diabetic kidney proteome through the use of the db/db mouse model system and mass spectrometry (MS). Multivariate analyses revealed distinct effects of insulin and liraglutide on the db/db kidney proteome, which was seen on the protein levels of, for example, pterin-4 α-carbinolamine dehydratase/dimerization cofactor of hepatocyte nuclear factor-1α (PCBD1), neural precursor cell expressed developmentally down-regulated-8 (NEDD8), transcription elongation factor-B polypeptide-1 (ELOC) and hepcidin (HEPC)...
March 2017: Physiological Reports
Marta Batllori, Marta Molero-Luis, Mercedes Casado, Cristina Sierra, Rafael Artuch, Aida Ormazabal
In this article, we review the state-of-the-art analysis of different biomarkers in the cerebrospinal fluid for the diagnosis of genetically conditioned, rare, neurometabolic diseases, including glucose transport defects, neurotransmitter (dopamine, serotonin, and gamma-aminobutyric acid) and pterin deficiencies, and vitamin defects (folate, vitamin B6, and thiamine) that affect the brain. The analysis of several key metabolites are detailed, which thus highlights the preanalytical and analytical factors that should be cautiously controlled to avoid misdiagnosis; moreover, these factors may facilitate an adequate interpretation of the biochemical profiles in the context of severe neuropediatric disorders...
November 2016: Seminars in Pediatric Neurology
N Liu, D H Zhao, X L Li, L X Cui, Q H Wu, M Jiang, X D Kong
Objective: To analyze the variations of PTPS gene in patients with suspected 6-pyruvoyl-tetra hydropterin synthase deficiency (PTPSD) and to make prenatal diagnosis in high-risk families. Methods: Chemiluminescence was used for phenylalanine detection in blood or dried blood spots.Patients with phenylalanine concentration over 120 μmol/L were detected by urine pterin analysis, and the activity of dihydropteridine reductase (DHPR) was detected. tetrahydrobiopterin loading tests were performed in suspected patients with abnormal urinary pterin profiles...
December 25, 2016: Zhonghua Fu Chan Ke za Zhi
Bishnu P Subedi, Paul F Fitzpatrick
The pterin-dependent aromatic amino acid hydroxylases are non-heme iron enzymes that catalyze the hydroxylation of the aromatic side chain of their respective substrates using an Fe(IV)O intermediate. While the eukaryotic enzymes are homotetramers with complex regulatory properties, bacterial phenylalanine hydroxylases are monomers that lack regulatory domains. As a result, the bacterial enzymes are more tractable for mechanistic studies. Using single turnover methods, the complete kinetic mechanism and intrinsic rate constants for Chromobacterium violaceum phenylalanine hydroxylase have been determined with both tetrahydrobiopterin and 6-methyltetrahyropterin as substrates...
December 13, 2016: Biochemistry
Fabricio Ragone, Héctor H Martínez Saavedra, Pablo F García, Ezequiel Wolcan, Gerardo A Argüello, Gustavo T Ruiz
A new synthetic route to acquire the water soluble complex fac-Re(I)(CO)3(pterin)(H2O) was carried out in aqueous solution. The complex has been obtained with success via the fac-[Re(I)(CO)3(H2O)3]Cl precursor complex. Re(I)(CO)3(pterin)(H2O) has been found to bind strongly with bovine and human serum albumins (BSA and HSA) with intrinsic-binding constants, Kb, of 6.5 × 10(5) M(-1) and 5.6 × 10(5) M(-1) at 310 K, respectively. The interactions of serum albumins with Re(I)(CO)3(pterin)(H2O) were evaluated employing UV-vis fluorescence and absorption spectroscopy and circular dichroism...
January 2017: Journal of Biological Inorganic Chemistry: JBIC
Anja D Hartmann, Natalie Wilhelm, Volker Erfle, Katrin Hartmann
OBJECTIVE: The bee venom melittin shows an antiviral efficacy against the human immunodeficiency virus in cell culture. It was shown to be non-toxic for cats. Aim of this pilot study was to investigate the clinical efficacy and side-effects of melittin in cats naturally infected with feline immunodeficiency virus (FIV). MATERIAL AND METHODS: The study was performed as a prospective, placebo-controlled double-blinded trial. Twenty cats were included, of which 10 cats each were treated with either melittin (500 µg/kg body weight) or phosphate-buffered saline (placebo) subcutaneously twice per week...
December 5, 2016: Tierärztliche Praxis. Ausgabe K, Kleintiere/Heimtiere
Nick A Kuburich, Nirakar Adhikari, Jeffrey A Hadwiger
Amoeba often use cell movement as a mechanism to find food, such as bacteria, in their environment. The chemotactic movement of the soil amoeba Dictyostelium to folate or other pterin compounds released by bacteria is a well-documented foraging mechanism. Acanthamoeba can also feed on bacteria but relatively little is known about the mechanism(s) by which this amoeba locates bacteria. Acanthamoeba movement in the presence of folate or bacteria was analyzed in above agar assays and compared to that observed for Dictyostelium...
December 2016: Protist
Carolina Castaño, Mariana Vignoni, Patricia Vicendo, Esther Oliveros, Andrés H Thomas
Pterin derivatives are involved in various biological functions, including enzymatic processes that take place in human skin. Unconjugated oxidized pterins are efficient photosensitizers under UV-A irradiation and accumulate in the skin of patients suffering from vitiligo, a chronic depigmentation disorder. These compounds are able to photoinduce the oxidation of the peptide α-melanocyte-stimulating hormone (α-MSH), which stimulates the production and release of melanin by melanocytes in skin and hair. In the present work we have used two peptides in which the amino acid sequence of α-MSH was mutated to specifically investigate the reactivity of tryptophan (Trp) and tyrosine residues (Tyr)...
November 2016: Journal of Photochemistry and Photobiology. B, Biology
Ryota Saito, Saori Suzuki, Kaname Sasaki
Aldose reductase is related to the onset and progression of diabetic complications, such as neuropathy, retinopathy, angiopathy, and so on: therefore molecules that are capable of inhibiting the enzyme are potential drugs for treatment of diabetic complications. Epalrestat is the sole aldose reductase inhibitor that is clinically used, but still has some drawbacks. Thus, the development of new aldose reductase inhibitors is still desired. We have synthesized a series of new pterin-7-carboxamides, and evaluated their in vitro inhibitory activities against human aldose reductase...
October 15, 2016: Bioorganic & Medicinal Chemistry Letters
Cheng-Hua Wang, Chong Zhang, Xin-Hui Xing
Xanthine dehydrogenase (EC, XDH) is a typical and complex molybdenum-containing flavoprotein which has been extensively studied for over 110 years. This enzyme catalyzes the oxidation of purines, pterin and aldehydes with NAD(+) or NADP(+) as electron acceptor, and sometimes can be transformed to xanthine oxidase (EC, XOD) capable of utilizing oxygen as the electron acceptor. XDHs are widely distributed in all eukarya, bacteria and archaea domains, and are proposed to play significant roles in various cellular processes, including purine catabolism and production of reactive oxygen species (ROS) and nitric oxide (NO) in both physiological and pathological contexts...
November 2016: Bioengineered
Lara O Reid, Ernesto A Roman, Andrés H Thomas, M Laura Dántola
Human serum albumin (HSA) is the most abundant protein in the circulatory system. Oxidized albumin was identified in the skin of patients suffering from vitiligo, a depigmentation disorder in which the protection against ultraviolet (UV) radiation fails because of the lack of melanin. Oxidized pterins, efficient photosensitizers under UV-A irradiation, accumulate in the skin affected by vitiligo. In this work, we have investigated the ability of pterin (Ptr), the parent compound of oxidized pterins, to induce structural and chemical changes in HSA under UV-A irradiation...
August 30, 2016: Biochemistry
Charles G Young
This review focuses on the synthesis, properties and electron paramagnetic resonance (EPR), electron spin echo envelope modulation (ESEEM) and electron-nuclear double resonance (ENDOR) spectroscopy of mononuclear d(1) oxo- and sulfido-Mo(V) complexes relevant to the understanding of the EPR-active Mo(V) forms of pterin-containing molybdenum enzymes.
June 4, 2016: Journal of Inorganic Biochemistry
Ying Zhao, William R Shadrick, Miranda J Wallace, Yinan Wu, Elizabeth C Griffith, Jianjun Qi, Mi-Kyung Yun, Stephen W White, Richard E Lee
The sulfonamide class of antibiotics has been in continuous use for over 70years. They are thought to act by directly inhibiting dihydropteroate synthase (DHPS), and also acting as prodrugs that sequester pterin pools by forming dead end pterin-sulfonamide conjugates. In this study, eight pterin-sulfonamide conjugates were synthesized using a novel synthetic strategy and their biochemical and microbiological properties were investigated. The conjugates were shown to competitively inhibit DHPS, and inhibition was enhanced by the presence of pyrophosphate that is crucial to catalysis and is known to promote an ordering of the DHPS active site...
August 15, 2016: Bioorganic & Medicinal Chemistry Letters
Hiroumi Mitome, Tomoya Ishizuka, Hiroaki Kotani, Yoshihito Shiota, Kazunari Yoshizawa, Takahiko Kojima
A ruthenium(II) complex, [Ru(dmdmp)Cl(MeBPA)] (2) (Hdmdmp = N,N-dimethyl-6,7-dimethylpterin, MeBPA = N-methyl-N,N-bis(pyridylmethyl)amine), having a pterin derivative as a proton-accepting ligand, was synthesized and characterized. Complex 2 shows higher basicity than that of a previously reported Ru(II)-pterin complex, [Ru(dmdmp) (TPA)](+) (1) (TPA = tris(2-pyridylmethyl)amine). On the other hand, 1e(-)-oxidized species of 1 (1OX) exhibits higher electron-acceptability than that of 1e(-)-oxidized 2 (2OX). Bond dissociation enthalpies (BDE) of the two Ru(II) complexes having Hdmdmp as a ligand in proton-coupled electron transfer (PCET) to generate 1OX and 2OX were calculated to be 85 kcal mol(-1) for 1OX and 78 kcal mol(-1) for 2OX...
August 3, 2016: Journal of the American Chemical Society
L Tinel, S Rossignol, R Ciuraru, S Dumas, C George
Pterins, derivatives of 2-aminopteridin-4(3H)-one, are natural photosensitizers, common to many biological systems. Indications that these photosensitizers are also present in the sea-surface microlayer motivated the study of the photophysical and photochemical properties of 6-carboxypterin (CPT), which was chosen as a model for this group of photoactive compounds. The kinetics of excited CPT in the singlet and triplet state in the presence of halides and organics were studied in aqueous solutions at neutral pH by means of steady-state fluorescence and laser-flash photolysis...
June 22, 2016: Physical Chemistry Chemical Physics: PCCP
Erland Arning, Teodoro Bottiglieri
No abstract text is available yet for this article.
June 8, 2016: JIMD Reports
Shohreh Khatami, Soghra Rouhi Dehnabeh, Sirous Zeinali, Beat Thöny, Mohammadreza Alaei, Shadab Salehpour, Aria Setoodeh, Farzaneh Rohani, Fatemeh Hajivalizadeh, Ashraf Samavat
Hyperphenylalaninemia (HPA) is a condition caused by tetrahydrobiopterin (BH4) and phenylalanine hydroxylase (PAH) deficiencies. It is essential that differential diagnosis be conducted to distinguish these two causes of HPA, because BH4 deficiency is a more severe disease involving progressive neurologic deterioration. Based on the biological findings, HPA is defined as a plasma phenylalanine level of >2.0 mg/dl (>120 μmol/l). The National Biochemistry Reference Laboratory at the Pasteur Institute of Iran initiated BH4 deficiency screening tests for the first time during the implementation of a nationwide phenylketonuria (PKU) screening program...
2017: JIMD Reports
Audrey M Mat, Mickael Perrigault, Jean-Charles Massabuau, Damien Tran
Cryptochromes are flavin- and pterin-containing photoreceptors of the cryptochrome/photolyase family. They play critical roles in organisms, among are which light-dependent and light-independent roles in biological rhythms. The present work aimed at describing a cryptochrome gene in the oyster Crassostrea gigas by (i) a characterization and phylogenetic analysis and (ii) by studying its expression in the relationship to rhythmic valve behavior in different entrainment regimes. Cryptochrome expression was focused on the adductor muscle of the oyster, the effector of the valve behavior...
2016: Chronobiology International
E E Moreno-Medinilla, M D Mora-Ramirez, R Calvo-Medina, J Martinez-Anton
INTRODUCTION: A deficiency of the enzyme guanosine triphosphate cyclohydrolase I (GTPCH 1) causes a reduction in the synthesis of tetrahydrobiopterin (BH4), a cofactor that is essential in the synthesis of tyrosine, dopamine and serotonin. It is an infrequent disease that produces psychomotor delay or regression and movement disorders, although treatment can improve or even correct the clinical signs and symptoms. CASE REPORT: We report the case of a girl with autosomal recessive GTPCH deficiency, who was diagnosed at 14 months by means of an analysis of the cerebrospinal fluid with pterin, HVA and 5-HIAA deficiency, and positive phenylalanine overload test and genetic study...
June 1, 2016: Revista de Neurologia
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