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Publisher: Springer-Verlag (Total: 2352 journals)

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Showing 1 - 200 of 2352 Journals sorted alphabetically
3D Printing in Medicine     Open Access   (Followers: 1)
3D Research     Hybrid Journal   (Followers: 21, SJR: 0.222, CiteScore: 1)
4OR: A Quarterly J. of Operations Research     Hybrid Journal   (Followers: 10, SJR: 0.825, CiteScore: 1)
AAPS J.     Hybrid Journal   (Followers: 23, SJR: 1.118, CiteScore: 4)
AAPS PharmSciTech     Hybrid Journal   (Followers: 7, SJR: 0.752, CiteScore: 3)
Abdominal Imaging     Hybrid Journal   (Followers: 16, SJR: 0.866, CiteScore: 2)
Abhandlungen aus dem Mathematischen Seminar der Universitat Hamburg     Hybrid Journal   (Followers: 4, SJR: 0.439, CiteScore: 0)
Academic Psychiatry     Full-text available via subscription   (Followers: 27, SJR: 0.53, CiteScore: 1)
Academic Questions     Hybrid Journal   (Followers: 8, SJR: 0.106, CiteScore: 0)
Accreditation and Quality Assurance: J. for Quality, Comparability and Reliability in Chemical Measurement     Hybrid Journal   (Followers: 28, SJR: 0.316, CiteScore: 1)
Acoustical Physics     Hybrid Journal   (Followers: 11, SJR: 0.359, CiteScore: 1)
Acoustics Australia     Hybrid Journal   (SJR: 0.232, CiteScore: 1)
Acta Analytica     Hybrid Journal   (Followers: 7, SJR: 0.367, CiteScore: 0)
Acta Applicandae Mathematicae     Hybrid Journal   (Followers: 1, SJR: 0.675, CiteScore: 1)
Acta Biotheoretica     Hybrid Journal   (Followers: 4, SJR: 0.284, CiteScore: 1)
Acta Diabetologica     Hybrid Journal   (Followers: 19, SJR: 1.587, CiteScore: 3)
Acta Endoscopica     Hybrid Journal   (Followers: 1)
acta ethologica     Hybrid Journal   (Followers: 4, SJR: 0.769, CiteScore: 1)
Acta Geochimica     Hybrid Journal   (Followers: 7, SJR: 0.24, CiteScore: 1)
Acta Geodaetica et Geophysica     Hybrid Journal   (Followers: 3, SJR: 0.305, CiteScore: 1)
Acta Geophysica     Hybrid Journal   (Followers: 11, SJR: 0.312, CiteScore: 1)
Acta Geotechnica     Hybrid Journal   (Followers: 7, SJR: 1.588, CiteScore: 3)
Acta Informatica     Hybrid Journal   (Followers: 5, SJR: 0.517, CiteScore: 1)
Acta Mathematica     Hybrid Journal   (Followers: 12, SJR: 7.066, CiteScore: 3)
Acta Mathematica Hungarica     Hybrid Journal   (Followers: 2, SJR: 0.452, CiteScore: 1)
Acta Mathematica Sinica, English Series     Hybrid Journal   (Followers: 6, SJR: 0.379, CiteScore: 1)
Acta Mathematica Vietnamica     Hybrid Journal   (SJR: 0.27, CiteScore: 0)
Acta Mathematicae Applicatae Sinica, English Series     Hybrid Journal   (SJR: 0.208, CiteScore: 0)
Acta Mechanica     Hybrid Journal   (Followers: 21, SJR: 1.04, CiteScore: 2)
Acta Mechanica Sinica     Hybrid Journal   (Followers: 5, SJR: 0.607, CiteScore: 2)
Acta Metallurgica Sinica (English Letters)     Hybrid Journal   (Followers: 7, SJR: 0.576, CiteScore: 2)
Acta Meteorologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.638, CiteScore: 1)
Acta Neurochirurgica     Hybrid Journal   (Followers: 7, SJR: 0.822, CiteScore: 2)
Acta Neurologica Belgica     Hybrid Journal   (Followers: 1, SJR: 0.376, CiteScore: 1)
Acta Neuropathologica     Hybrid Journal   (Followers: 4, SJR: 7.589, CiteScore: 12)
Acta Oceanologica Sinica     Hybrid Journal   (Followers: 3, SJR: 0.334, CiteScore: 1)
Acta Physiologiae Plantarum     Hybrid Journal   (Followers: 2, SJR: 0.574, CiteScore: 2)
Acta Politica     Hybrid Journal   (Followers: 15, SJR: 0.605, CiteScore: 1)
Activitas Nervosa Superior     Hybrid Journal   (SJR: 0.147, CiteScore: 0)
adhäsion KLEBEN & DICHTEN     Hybrid Journal   (Followers: 8, SJR: 0.103, CiteScore: 0)
ADHD Attention Deficit and Hyperactivity Disorders     Hybrid Journal   (Followers: 25, SJR: 0.72, CiteScore: 2)
Adhesion Adhesives & Sealants     Hybrid Journal   (Followers: 9)
Administration and Policy in Mental Health and Mental Health Services Research     Partially Free   (Followers: 17, SJR: 1.005, CiteScore: 2)
Adsorption     Hybrid Journal   (Followers: 4, SJR: 0.703, CiteScore: 2)
Advances in Applied Clifford Algebras     Hybrid Journal   (Followers: 4, SJR: 0.698, CiteScore: 1)
Advances in Atmospheric Sciences     Hybrid Journal   (Followers: 37, SJR: 0.956, CiteScore: 2)
Advances in Computational Mathematics     Hybrid Journal   (Followers: 19, SJR: 0.812, CiteScore: 1)
Advances in Contraception     Hybrid Journal   (Followers: 3)
Advances in Data Analysis and Classification     Hybrid Journal   (Followers: 58, SJR: 1.09, CiteScore: 1)
Advances in Gerontology     Partially Free   (Followers: 8, SJR: 0.144, CiteScore: 0)
Advances in Health Sciences Education     Hybrid Journal   (Followers: 30, SJR: 1.64, CiteScore: 2)
Advances in Manufacturing     Hybrid Journal   (Followers: 4, SJR: 0.475, CiteScore: 2)
Advances in Polymer Science     Hybrid Journal   (Followers: 45, SJR: 1.04, CiteScore: 3)
Advances in Therapy     Hybrid Journal   (Followers: 5, SJR: 1.075, CiteScore: 3)
Aegean Review of the Law of the Sea and Maritime Law     Hybrid Journal   (Followers: 6)
Aequationes Mathematicae     Hybrid Journal   (Followers: 2, SJR: 0.517, CiteScore: 1)
Aerobiologia     Hybrid Journal   (Followers: 3, SJR: 0.673, CiteScore: 2)
Aesthetic Plastic Surgery     Hybrid Journal   (Followers: 11, SJR: 0.825, CiteScore: 1)
African Archaeological Review     Hybrid Journal   (Followers: 20, SJR: 0.862, CiteScore: 1)
Afrika Matematika     Hybrid Journal   (Followers: 1, SJR: 0.235, CiteScore: 0)
AGE     Hybrid Journal   (Followers: 7)
Ageing Intl.     Hybrid Journal   (Followers: 7, SJR: 0.39, CiteScore: 1)
Aggiornamenti CIO     Hybrid Journal   (Followers: 1)
Aging Clinical and Experimental Research     Hybrid Journal   (Followers: 3, SJR: 0.67, CiteScore: 2)
Agricultural Research     Hybrid Journal   (Followers: 6, SJR: 0.276, CiteScore: 1)
Agriculture and Human Values     Hybrid Journal   (Followers: 14, SJR: 1.173, CiteScore: 3)
Agroforestry Systems     Hybrid Journal   (Followers: 20, SJR: 0.663, CiteScore: 1)
Agronomy for Sustainable Development     Hybrid Journal   (Followers: 13, SJR: 1.864, CiteScore: 6)
AI & Society     Hybrid Journal   (Followers: 9, SJR: 0.227, CiteScore: 1)
AIDS and Behavior     Hybrid Journal   (Followers: 14, SJR: 1.792, CiteScore: 3)
Air Quality, Atmosphere & Health     Hybrid Journal   (Followers: 4, SJR: 0.862, CiteScore: 3)
Akupunktur & Aurikulomedizin     Full-text available via subscription   (Followers: 1)
Algebra and Logic     Hybrid Journal   (Followers: 6, SJR: 0.531, CiteScore: 0)
Algebra Universalis     Hybrid Journal   (Followers: 2, SJR: 0.583, CiteScore: 1)
Algebras and Representation Theory     Hybrid Journal   (Followers: 1, SJR: 1.095, CiteScore: 1)
Algorithmica     Hybrid Journal   (Followers: 9, SJR: 0.56, CiteScore: 1)
Allergo J.     Full-text available via subscription   (Followers: 1, SJR: 0.234, CiteScore: 0)
Allergo J. Intl.     Hybrid Journal   (Followers: 2)
Alpine Botany     Hybrid Journal   (Followers: 5, SJR: 1.11, CiteScore: 3)
ALTEX : Alternatives to Animal Experimentation     Open Access   (Followers: 3)
AMBIO     Hybrid Journal   (Followers: 10, SJR: 1.569, CiteScore: 4)
American J. of Cardiovascular Drugs     Hybrid Journal   (Followers: 16, SJR: 0.951, CiteScore: 3)
American J. of Community Psychology     Hybrid Journal   (Followers: 29, SJR: 1.329, CiteScore: 2)
American J. of Criminal Justice     Hybrid Journal   (Followers: 8, SJR: 0.772, CiteScore: 1)
American J. of Cultural Sociology     Hybrid Journal   (Followers: 16, SJR: 0.46, CiteScore: 1)
American J. of Dance Therapy     Hybrid Journal   (Followers: 4, SJR: 0.181, CiteScore: 0)
American J. of Potato Research     Hybrid Journal   (Followers: 2, SJR: 0.611, CiteScore: 1)
American J. of Psychoanalysis     Hybrid Journal   (Followers: 21, SJR: 0.314, CiteScore: 0)
American Sociologist     Hybrid Journal   (Followers: 14, SJR: 0.35, CiteScore: 0)
Amino Acids     Hybrid Journal   (Followers: 8, SJR: 1.135, CiteScore: 3)
AMS Review     Partially Free   (Followers: 4)
Analog Integrated Circuits and Signal Processing     Hybrid Journal   (Followers: 7, SJR: 0.211, CiteScore: 1)
Analysis and Mathematical Physics     Hybrid Journal   (Followers: 5, SJR: 0.536, CiteScore: 1)
Analysis in Theory and Applications     Hybrid Journal   (Followers: 1)
Analysis of Verbal Behavior     Hybrid Journal   (Followers: 6)
Analytical and Bioanalytical Chemistry     Hybrid Journal   (Followers: 32, SJR: 0.978, CiteScore: 3)
Anatomical Science Intl.     Hybrid Journal   (Followers: 3, SJR: 0.367, CiteScore: 1)
Angewandte Schmerztherapie und Palliativmedizin     Hybrid Journal  
Angiogenesis     Hybrid Journal   (Followers: 3, SJR: 2.177, CiteScore: 5)
Animal Cognition     Hybrid Journal   (Followers: 20, SJR: 1.389, CiteScore: 3)
Annales françaises de médecine d'urgence     Hybrid Journal   (Followers: 1, SJR: 0.192, CiteScore: 0)
Annales Henri Poincaré     Hybrid Journal   (Followers: 3, SJR: 1.097, CiteScore: 2)
Annales mathématiques du Québec     Hybrid Journal   (Followers: 4, SJR: 0.438, CiteScore: 0)
Annali dell'Universita di Ferrara     Hybrid Journal   (SJR: 0.429, CiteScore: 0)
Annali di Matematica Pura ed Applicata     Hybrid Journal   (Followers: 1, SJR: 1.197, CiteScore: 1)
Annals of Biomedical Engineering     Hybrid Journal   (Followers: 17, SJR: 1.042, CiteScore: 3)
Annals of Combinatorics     Hybrid Journal   (Followers: 4, SJR: 0.932, CiteScore: 1)
Annals of Data Science     Hybrid Journal   (Followers: 12)
Annals of Dyslexia     Hybrid Journal   (Followers: 10, SJR: 0.85, CiteScore: 2)
Annals of Finance     Hybrid Journal   (Followers: 32, SJR: 0.579, CiteScore: 1)
Annals of Forest Science     Hybrid Journal   (Followers: 7, SJR: 0.986, CiteScore: 2)
Annals of Global Analysis and Geometry     Hybrid Journal   (Followers: 1, SJR: 1.228, CiteScore: 1)
Annals of Hematology     Hybrid Journal   (Followers: 15, SJR: 1.043, CiteScore: 2)
Annals of Mathematics and Artificial Intelligence     Hybrid Journal   (Followers: 12, SJR: 0.413, CiteScore: 1)
Annals of Microbiology     Hybrid Journal   (Followers: 11, SJR: 0.479, CiteScore: 2)
Annals of Nuclear Medicine     Hybrid Journal   (Followers: 4, SJR: 0.687, CiteScore: 2)
Annals of Operations Research     Hybrid Journal   (Followers: 10, SJR: 0.943, CiteScore: 2)
Annals of Ophthalmology     Hybrid Journal   (Followers: 12)
Annals of Regional Science     Hybrid Journal   (Followers: 8, SJR: 0.614, CiteScore: 1)
Annals of Software Engineering     Hybrid Journal   (Followers: 13)
Annals of Solid and Structural Mechanics     Hybrid Journal   (Followers: 9, SJR: 0.239, CiteScore: 1)
Annals of Surgical Oncology     Hybrid Journal   (Followers: 14, SJR: 1.986, CiteScore: 4)
Annals of Telecommunications     Hybrid Journal   (Followers: 9, SJR: 0.223, CiteScore: 1)
Annals of the Institute of Statistical Mathematics     Hybrid Journal   (Followers: 1, SJR: 1.495, CiteScore: 1)
Antonie van Leeuwenhoek     Hybrid Journal   (Followers: 5, SJR: 0.834, CiteScore: 2)
Apidologie     Hybrid Journal   (Followers: 4, SJR: 1.22, CiteScore: 3)
APOPTOSIS     Hybrid Journal   (Followers: 9, SJR: 1.424, CiteScore: 4)
Applicable Algebra in Engineering, Communication and Computing     Hybrid Journal   (Followers: 3, SJR: 0.294, CiteScore: 1)
Applications of Mathematics     Hybrid Journal   (Followers: 2, SJR: 0.602, CiteScore: 1)
Applied Biochemistry and Biotechnology     Hybrid Journal   (Followers: 45, SJR: 0.571, CiteScore: 2)
Applied Biochemistry and Microbiology     Hybrid Journal   (Followers: 18, SJR: 0.21, CiteScore: 1)
Applied Categorical Structures     Hybrid Journal   (Followers: 3, SJR: 0.49, CiteScore: 0)
Applied Composite Materials     Hybrid Journal   (Followers: 49, SJR: 0.58, CiteScore: 2)
Applied Entomology and Zoology     Partially Free   (Followers: 5, SJR: 0.422, CiteScore: 1)
Applied Geomatics     Hybrid Journal   (Followers: 3, SJR: 0.733, CiteScore: 3)
Applied Geophysics     Hybrid Journal   (Followers: 8, SJR: 0.488, CiteScore: 1)
Applied Intelligence     Hybrid Journal   (Followers: 13, SJR: 0.6, CiteScore: 2)
Applied Magnetic Resonance     Hybrid Journal   (Followers: 4, SJR: 0.319, CiteScore: 1)
Applied Mathematics & Optimization     Hybrid Journal   (Followers: 8, SJR: 0.886, CiteScore: 1)
Applied Mathematics - A J. of Chinese Universities     Hybrid Journal   (SJR: 0.17, CiteScore: 0)
Applied Mathematics and Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.461, CiteScore: 1)
Applied Microbiology and Biotechnology     Hybrid Journal   (Followers: 67, SJR: 1.182, CiteScore: 4)
Applied Physics A     Hybrid Journal   (Followers: 10, SJR: 0.481, CiteScore: 2)
Applied Physics B: Lasers and Optics     Hybrid Journal   (Followers: 24, SJR: 0.74, CiteScore: 2)
Applied Psychophysiology and Biofeedback     Hybrid Journal   (Followers: 8, SJR: 0.519, CiteScore: 2)
Applied Research in Quality of Life     Hybrid Journal   (Followers: 12, SJR: 0.316, CiteScore: 1)
Applied Solar Energy     Hybrid Journal   (Followers: 21, SJR: 0.225, CiteScore: 0)
Applied Spatial Analysis and Policy     Hybrid Journal   (Followers: 6, SJR: 0.542, CiteScore: 1)
Aquaculture Intl.     Hybrid Journal   (Followers: 26, SJR: 0.591, CiteScore: 2)
Aquarium Sciences and Conservation     Hybrid Journal   (Followers: 2)
Aquatic Ecology     Hybrid Journal   (Followers: 36, SJR: 0.656, CiteScore: 2)
Aquatic Geochemistry     Hybrid Journal   (Followers: 4, SJR: 0.591, CiteScore: 1)
Aquatic Sciences     Hybrid Journal   (Followers: 13, SJR: 1.109, CiteScore: 3)
Arabian J. for Science and Engineering     Hybrid Journal   (Followers: 5, SJR: 0.303, CiteScore: 1)
Arabian J. of Geosciences     Hybrid Journal   (Followers: 2, SJR: 0.319, CiteScore: 1)
Archaeological and Anthropological Sciences     Hybrid Journal   (Followers: 21, SJR: 1.052, CiteScore: 2)
Archaeologies     Hybrid Journal   (Followers: 12, SJR: 0.224, CiteScore: 0)
Archiv der Mathematik     Hybrid Journal   (Followers: 1, SJR: 0.725, CiteScore: 1)
Archival Science     Hybrid Journal   (Followers: 63, SJR: 0.745, CiteScore: 2)
Archive for History of Exact Sciences     Hybrid Journal   (Followers: 7, SJR: 0.186, CiteScore: 1)
Archive for Mathematical Logic     Hybrid Journal   (Followers: 3, SJR: 0.909, CiteScore: 1)
Archive for Rational Mechanics and Analysis     Hybrid Journal   (SJR: 3.93, CiteScore: 3)
Archive of Applied Mechanics     Hybrid Journal   (Followers: 5, SJR: 0.79, CiteScore: 2)
Archives and Museum Informatics     Hybrid Journal   (Followers: 149, SJR: 0.101, CiteScore: 0)
Archives of Computational Methods in Engineering     Hybrid Journal   (Followers: 5, SJR: 1.41, CiteScore: 5)
Archives of Dermatological Research     Hybrid Journal   (Followers: 7, SJR: 1.006, CiteScore: 2)
Archives of Environmental Contamination and Toxicology     Hybrid Journal   (Followers: 14, SJR: 0.773, CiteScore: 2)
Archives of Gynecology and Obstetrics     Hybrid Journal   (Followers: 17, SJR: 0.956, CiteScore: 2)
Archives of Microbiology     Hybrid Journal   (Followers: 9, SJR: 0.644, CiteScore: 2)
Archives of Orthopaedic and Trauma Surgery     Hybrid Journal   (Followers: 9, SJR: 1.146, CiteScore: 2)
Archives of Osteoporosis     Hybrid Journal   (Followers: 2, SJR: 0.71, CiteScore: 2)
Archives of Sexual Behavior     Hybrid Journal   (Followers: 10, SJR: 1.493, CiteScore: 3)
Archives of Toxicology     Hybrid Journal   (Followers: 17, SJR: 1.541, CiteScore: 5)
Archives of Virology     Hybrid Journal   (Followers: 5, SJR: 0.973, CiteScore: 2)
Archives of Women's Mental Health     Hybrid Journal   (Followers: 15, SJR: 1.274, CiteScore: 3)
Archivio di Ortopedia e Reumatologia     Hybrid Journal  
Archivum Immunologiae et Therapiae Experimentalis     Hybrid Journal   (Followers: 2, SJR: 0.946, CiteScore: 3)
ArgoSpine News & J.     Hybrid Journal  
Argumentation     Hybrid Journal   (Followers: 6, SJR: 0.349, CiteScore: 1)
Arid Ecosystems     Hybrid Journal   (Followers: 2, SJR: 0.2, CiteScore: 0)
Arkiv för Matematik     Hybrid Journal   (Followers: 1, SJR: 0.766, CiteScore: 1)
Arnold Mathematical J.     Hybrid Journal   (Followers: 1, SJR: 0.355, CiteScore: 0)
Arthropod-Plant Interactions     Hybrid Journal   (Followers: 2, SJR: 0.839, CiteScore: 2)
Arthroskopie     Hybrid Journal   (Followers: 1, SJR: 0.131, CiteScore: 0)
Artificial Intelligence and Law     Hybrid Journal   (Followers: 11, SJR: 0.937, CiteScore: 2)
Artificial Intelligence Review     Hybrid Journal   (Followers: 18, SJR: 0.833, CiteScore: 4)
Artificial Life and Robotics     Hybrid Journal   (Followers: 9, SJR: 0.226, CiteScore: 0)
Asia Europe J.     Hybrid Journal   (Followers: 5, SJR: 0.504, CiteScore: 1)
Asia Pacific Education Review     Hybrid Journal   (Followers: 12, SJR: 0.479, CiteScore: 1)
Asia Pacific J. of Management     Hybrid Journal   (Followers: 16, SJR: 1.185, CiteScore: 2)
Asia-Pacific Education Researcher     Hybrid Journal   (Followers: 13, SJR: 0.353, CiteScore: 1)
Asia-Pacific Financial Markets     Hybrid Journal   (Followers: 2, SJR: 0.187, CiteScore: 0)
Asia-Pacific J. of Atmospheric Sciences     Hybrid Journal   (Followers: 19, SJR: 0.855, CiteScore: 1)
Asian Business & Management     Hybrid Journal   (Followers: 9, SJR: 0.378, CiteScore: 1)
Asian J. of Business Ethics     Hybrid Journal   (Followers: 9)
Asian J. of Criminology     Hybrid Journal   (Followers: 6, SJR: 0.543, CiteScore: 1)
AStA Advances in Statistical Analysis     Hybrid Journal   (Followers: 3, SJR: 0.548, CiteScore: 1)
AStA Wirtschafts- und Sozialstatistisches Archiv     Hybrid Journal   (Followers: 5, SJR: 0.183, CiteScore: 0)
ästhetische dermatologie & kosmetologie     Full-text available via subscription  
Astronomy and Astrophysics Review     Hybrid Journal   (Followers: 22, SJR: 3.385, CiteScore: 5)

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Journal Cover
Amino Acids
Journal Prestige (SJR): 1.135
Citation Impact (citeScore): 3
Number of Followers: 8  
 
  Hybrid Journal Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1438-2199 - ISSN (Online) 0939-4451
Published by Springer-Verlag Homepage  [2352 journals]
  • Effects of beta-alanine supplementation on muscle function during recovery
           from resistance exercise in young adults
    • Authors: Mirela Casonato Roveratti; Jeferson Lucas Jacinto; Douglas Bendito Oliveira; Rubens Alexandre da Silva; Rodrigo Antonio Carvalho Andraus; Erick Prado de Oliveira; Alex Silva Ribeiro; Andreo Fernando Aguiar
      Abstract: β-Alanine supplementation has been shown to increase muscle carnosine levels and exercise performance. However, its effects on muscle recovery from resistance exercise (RE) remains unknown. The purpose of this study was to investigate the effects of β-alanine supplementation on muscle function during recovery from a single session of high-intensity RE. Twenty-four untrained young adults (22.1 ± 4.6 years old) were assigned to one of two groups (N = 12 per group): a placebo-supplement group (4.8 g/day) or an β-alanine-supplement group (4.8 g/day). The groups completed a single session of high-intensity RE after 28 days of supplementation and were then evaluated for muscle function on the three subsequent days (at 24, 48, and 72 h postexercise) to assess the time course of muscle recovery. The following indicators of muscle recovery were assessed: number of repetitions until failure, rating of perceived exertion, muscle soreness, and blood levels of creatine kinase (CK). Number of repetitions until failure increased from 24 to 48 h and 72 h of recovery (time P < 0.01), with no difference between groups. There was a significant increase in the rating of perceived exertion among the sets during the RE session (time P < 0.01), with no difference between the groups. No difference was observed over time and between groups in rating of perceived exertion in the functional tests during recovery period. Blood CK levels and muscle soreness increased at 24 h postexercise and then progressively declined at 48 and 72 h postexercise, respectively (time P < 0.05), with no difference between groups. In conclusion, our data indicate that β-alanine supplementation does not improve muscle recovery following a high-intensity RE session in untrained young adults.
      PubDate: 2019-01-09
      DOI: 10.1007/s00726-018-02686-y
       
  • An update on carnosine and anserine research
    • Authors: Wim Derave; Barbora De Courten; Shahid Baba
      PubDate: 2019-01-07
      DOI: 10.1007/s00726-018-02689-9
       
  • Carnosinase concentration, activity, and CNDP1 genotype in patients with
           type 2 diabetes with and without nephropathy
    • Authors: Shiqi Zhang; Thomas Albrecht; Angelica Rodriguez-Niño; Jiedong Qiu; Peter Schnuelle; Verena Peters; Claus Peter Schmitt; Jacob van den Born; Stephan J. L. Bakker; Alexander Lammert; Bernhard K. Krämer; Benito A. Yard; Sibylle J. Hauske
      Abstract: This study assessed if serum carnosinase (CNDP1) activity and concentration in patients with type 2 diabetes mellitus (T2D) with diabetic nephropathy (DN) differs from those without nephropathy. In a cross-sectional design 127 patients with T2D with DN ((CTG)5 homozygous patients n = 45) and 145 patients with T2D without nephropathy ((CTG)5 homozygous patients n = 47) were recruited. Univariate and multivariate regression analyses were performed to predict factors relevant for serum CNDP1 concentration. CNDP1 (CTG)5 homozygous patients with T2D with DN had significantly lower CNDP1 concentrations (30.4 ± 18.3 vs 51.2 ± 17.6 µg/ml, p < 0.05) and activity (1.25 ± 0.5 vs 2.53 ± 1.1 µmol/ml/h, p < 0.05) than those without nephropathy. This applied for patients with DN on the whole, irrespective of (CTG)5 homozygosity. In the multivariate regression analyses, lower serum CNDP1 concentrations correlated with impaired renal function and to a lesser extend with the CNDP1 genotype (95% CI of regression coefficients: eGFR: 0.10–1.94 (p = 0.001); genotype: − 0.05 to 5.79 (p = 0.055)). Our study demonstrates that serum CNDP1 concentrations associate with CNDP1 genotype and renal function in patients with T2D. Our data warrant further studies using large cohorts to confirm these findings and to delineate the correlation between low serum CNDP1 concentrations and renal function deterioration in patients with T2D.
      PubDate: 2019-01-04
      DOI: 10.1007/s00726-018-02692-0
       
  • GC–MS measurement of biological N G -hydroxy- l -arginine, a
           stepmotherly investigated endogenous nitric oxide synthase substrate and
           arginase inhibitor
    • Authors: Alexander Bollenbach; Stephan J. L. Bakker; Dimitrios Tsikas
      Abstract: l-Arginine is converted by nitric oxide synthase (NOS) to l-citrulline and nitric oxide (NO). NG-Hydroxy-l-arginine (NOHA) is the isolable intermediate of this reaction. NOHA has been identified in biological samples by gas chromatography–mass spectrometry (GC–MS) and quantified by high-performance liquid chromatography (HPLC). Reportedly, NOHA concentrations in human plasma and serum range over four orders of magnitude (e.g., 2 nM–34 µM). The natural occurrence of NOHA in urine has not been reported thus far. Here, we report a validated stable-isotope dilution GC–MS method for the quantitative determination of NOHA in 10-µL aliquots of human serum and urine samples. The method is based on a two-step derivatization of NOHA to the methyl ester pentafluoropropionyl (PFP) derivatives using newly synthesized trideuteromethyl ester NOHA (d3Me-NOHA) as the internal standard and GC–MS quantification. NOHA was found to form a methyl ester-NG,Nδ,Nα-pentafluoropropionyl derivative, i.e., Me-(PFP)3 (M, 642) with the NG-hydroxy group remaining non-derivatized. Selected-ion monitoring of mass-to-charge (m/z) ratio of 458 for endogenous NOHA and m/z 461 for d3Me-NOHA in the negative-ion chemical ionization mode revealed NOHA concentrations of the order of 0.2 µM in human serum and 3 µM in urine samples. Accuracy (recovery, %) was 91.6 ± 1.6% in serum and 39.9 ± 4.5% in urine. Inorganic nitrate was found to decrease NOHA recovery from urine presumably through the reaction of the OH group of NOHA with nitric acid. Imprecision (RSD,  %) ranged between 1.4 and 14.8% in serum, and between 5.3 and 18.4% in urine in the investigated concentration range (0–15 µM NOHA). Ten healthy kidney donors excreted in the urine (mean ± SEM) 13.9 ± 1.81 µmol NOHA per day before and 10.9 ± 1.4 µmol NOHA per day after kidney donation (P = 0.24). Similar results were observed for dimethylamine (DMA), the major urinary metabolite of asymmetric dimethylarginine (ADMA). Changes in NOHA and DMA correlated positively (r = 0.718, P = 0.019). This is the first report on the occurrence and measurement of NOHA in human urine and on the effect of human unilateral nephrectomy on urinary NOHA and DMA. Healthy kidney donation may be useful as a model for kidney disease.
      PubDate: 2019-01-04
      DOI: 10.1007/s00726-018-02695-x
       
  • Effect of renal function on homeostasis of asymmetric dimethylarginine
           (ADMA): studies in donors and recipients of renal transplants
    • Authors: M. Yusof Said; Rianne M. Douwes; Marco van Londen; Isidor Minović; Anne-Roos Frenay; Martin H. de Borst; Else van den Berg; M. Rebecca Heiner-Fokkema; Arslan Arinc Kayacelebi; Alexander Bollenbach; Harry van Goor; Gerjan Navis; Dimitrios Tsikas; Stephan J. L. Bakker
      Abstract: Asymmetric dimethylarginine (ADMA) is a methylated form of arginine and an endogenous nitric oxide synthase inhibitor. Renal function decline is associated with increase of plasma ADMA in chronic kidney disease populations. It is yet unknown how isolated renal function impairment affects ADMA homeostasis in healthy humans. Here, we measured plasma concentrations and urinary excretion of ADMA using GC–MS/MS in 130 living kidney donors before and at 1.6 (1.6–1.9) months after donation. We additionally analyzed 201 stable renal transplant recipients (RTR) that were included > 1 year after transplantation, as a model for kidney disease in the context of single kidney state. We measured true glomerular filtration rate (mGFR) using 125I-iothalamate. To study enzymatic metabolism of ADMA, we also measured l-citrulline as primary metabolite. Mean age was 52 ± 10 years in donors and 54 ± 12 years in RTR. Renal function was significantly reduced from pre- to post-donation (mGFR: 104 ± 17 vs. 66 ± 10 ml/min per 1.73 m2 BSA, − 36 ± 7%, P < 0.001). Urinary ADMA excretion strongly and significantly decreased from pre- to post-donation (60.6 ± 16.0 vs. 40.5 ± 11.5 µmol/24 h, − 31.5 ± 21.5%, P < 0.001), while plasma ADMA increased only slightly (0.53 ± 0.08 vs. 0.58 ± 0.09 µM, 11.1 ± 20.1%, P < 0.001). Compared to donors post-donation, RTR had significantly worse renal function (mGFR: 49 ± 18 ml/min/1.73 m2, − 25 ± 2%, P < 0.001) and lower urinary ADMA excretion (30.9 ± 12.4 µmol/24 h, − 23.9 ± 3.4%, P < 0.001). Plasma ADMA in RTR (0.60 ± 0.11 µM) did not significantly differ from donors post-donation (2.9 ± 1.9%, P = 0.13). Plasma citrulline was inversely associated with mGFR (st. β: − 0.23, P < 0.001), consistent with increased ADMA metabolism to citrulline with lower GFR. In both groups, the response of urinary ADMA excretion to renal function loss was much larger than that of plasma ADMA. As citrulline was associated with GFR, our data indicate that with renal function impairment, a decrease in urinary ADMA excretion does not lead to a corresponding increase in plasma ADMA, likely due to enhanced metabolism, thus allowing for lower renal excretion of ADMA.
      PubDate: 2019-01-04
      DOI: 10.1007/s00726-018-02693-z
       
  • Development and validation of GC–MS methods for the comprehensive
           analysis of amino acids in plasma and urine and applications to the HELLP
           syndrome and pediatric kidney transplantation: evidence of altered
           methylation, transamidination, and arginase activity
    • Authors: Erik Hanff; Stephan Ruben; Martin Kreuzer; Alexander Bollenbach; Arslan Arinc Kayacelebi; Anibh Martin Das; Frauke von Versen-Höynck; Constantin von Kaisenberg; Dieter Haffner; Stefan Ückert; Dimitrios Tsikas
      Abstract: We developed and validated gas chromatography–mass spectrometry (GC–MS) methods for the simultaneous measurement of amino acids and their metabolites in 10-µL aliquots of human plasma and urine. De novo synthesized trideutero-methyl esters were used as internal standards. Plasma proteins were precipitated by acidified methanol and removed by centrifugation. Supernatants and native urine were evaporated to dryness. Amino acids were first esterified using 2 M HCl in methanol and then amidated using pentafluoropropionic anhydride for electron-capture negative-ion chemical ionization. Time programmes were used for the gas chromatograph oven and the selected-ion monitoring of specific anions. The GC–MS methods were applied in clinical studies on the HELLP syndrome and pediatric kidney transplantation (KTx) focusing on l-arginine-related pathways. We found lower sarcosine (N-methylglycine) and higher asymmetric dimethylarginine (ADMA) plasma concentrations in HELLP syndrome women (n = 7) compared to healthy pregnant women (n = 5) indicating altered methylation. In plasma of pediatric KTx patients, lower guanidinoacetate and homoarginine concentrations were found in plasma but not in urine samples of patients treated with standard mycophenolate mofetil-based immunosuppression (MMF; n = 22) in comparison to matched patients treated with MMF-free immunosuppression (n = 22). On average, the global arginine bioavailability ratio was by about 40% lower in the MMF group compared to the EVR group (P = 0.004). Mycophenolate, the major pharmacologically active metabolite of MMF, is likely to inhibit the arginine:glycine amidinotransferase (AGAT), and to enhance arginase activity in leukocytes and other types of cell of MMF-treated children.
      PubDate: 2019-01-02
      DOI: 10.1007/s00726-018-02688-w
       
  • Synthesis, characterization and anticonvulsant activity of new
           azobenzene-containing VV-hemorphin-5 bio photoswitch
    • Authors: Petar T. Todorov; Petia N. Peneva; Stela I. Georgieva; Jana Tchekalarova; Victoria Vitkova; Krassimira Antonova; Anton Georgiev
      Abstract: A novel analog of VV-hemorphin-5 containing azobenzene moiety has been synthesized and investigated for anticonvulsant activity in relation to its E → Z photophysical properties activated by long wavelength light at 365 nm. The synthesis was achieved by a modified SPPS by Fmoc-dimerization strategy. The electrochemical behavior before and after UV illumination was investigated using different voltammetric modes. The number of electrons transferred, heterogenic rate constant and diffusion coefficient for E- and Z-isomers were also evaluated. Revealing the governing principles involved in signaling and nerve pulse propagation requires the detailed characterization of the electrical properties of cell membranes. For probing the effect of synthesized azo-peptide on the membrane electrical properties, we measured the specific capacitance of lipid bilayers, representing a basic physical model of biomembranes with their simple reproducibility in laboratory conditions at controlled membrane composition and physicochemical parameters of the surrounding aqueous medium. Our results have shown reduced membrane capacitance in the presence of the azo-peptide, thus providing evidences for possible alterations in the dielectric permittivity of the bilayer. The (Val-Val-Tyr-Pro-Trp-Thr-Gln)2Azo peptide was explored also in vivo for preliminary anticonvulsant activity by using the 6-Hz seizure test and pentylenetetrazol (PTZ) seizure test in mice. The Z-isomer has exhibited higher potency compared to E-isomer most pronouncedly in the 6 Hz test for psychomotor seizures where the compound had activity at all three tested doses. It was found that the Z-isomer decrease the latency for onset of clonic seizures induced by PTZ. These results demonstrate that the Z-isomer deserves further evaluation in other screening tests for anticonvulsant activity.
      PubDate: 2019-01-02
      DOI: 10.1007/s00726-018-02691-1
       
  • Altered brain arginine metabolism in a mouse model of tauopathy
    • Authors: Pranav Vemula; Yu Jing; Hu Zhang; Jerry B. Hunt; Leslie A. Sandusky-Beltran; Daniel C. Lee; Ping Liu
      Abstract: Tauopathies consist of intracellular accumulation of hyperphosphorylated and aggregated microtubule protein tau, which remains a histopathological feature of Alzheimer’s disease (AD) and frontotemporal dementia. l-Arginine is a semi-essential amino acid with a number of bioactive molecules. Its downstream metabolites putrescine, spermidine, and spermine (polyamines) are critically involved in microtubule assembly and stabilization. Recent evidence implicates altered arginine metabolism in the pathogenesis of AD. Using high-performance liquid chromatographic and mass spectrometric assays, the present study systematically determined the tissue concentrations of l-arginine and its nine downstream metabolites in the frontal cortex, hippocampus, parahippocampal region, striatum, thalamus, and cerebellum in male PS19 mice-bearing human tau P301S mutation at 4, 8, and 12–14 months of age. As compared to their wild-type littermates, PS19 mice displayed early and/or prolonged increases in l-ornithine and altered polyamine levels with age. There were also genotype- and age-related changes in l-arginine, l-citrulline, glutamine, glutamate, and γ-aminobutyric acid in a region- and/or chemical-specific manner. The results demonstrate altered brain arginine metabolism in PS19 mice with the most striking changes in l-ornithine, polyamines, and glutamate, indicating a shift of l-arginine metabolism to favor the arginase–polyamine pathway. Given the role of polyamines in maintaining microtubule stability, the functional significance of these changes remains to be explored in future research.
      PubDate: 2019-01-02
      DOI: 10.1007/s00726-018-02687-x
       
  • Functionality of an absolutely conserved glycine residue in the chimeric
           relaxin family peptide R3/I5
    • Authors: Jia-Hui Wang; Xiao-Xia Shao; Meng-Jun Hu; Ya-Li Liu; Zeng-Guang Xu; Zhan-Yun Guo
      Abstract: The insulin superfamily is a group of homologous proteins that are further divided into the insulin family and relaxin family according to their distinct receptors. All insulin superfamily members contain three absolutely conserved disulfide linkages and a nonchiral Gly residue immediately following the first B-chain cysteine. The functionality of this conserved Gly residue in the insulin family has been studied by replacing it with natural l-amino acids or the corresponding unnatural d-amino acids. However, such analysis has not been conducted on relaxin family members. In the present study, we conducted chiral mutagenesis on the conserved B11Gly of the chimeric relaxin family peptide R3/I5, which is an efficient agonist for receptor RXFP3 and RXFP4. Similar to the effects on insulin family foldability, l-Ala or l-Ser substitution completely abolished the in vitro refolding of a recombinant R3/I5 precursor; whereas, d-Ala or d-Ser substitution had no detrimental effect on refolding of a semi-synthetic R3/I5 precursor, suggesting that the conserved Gly residue controls the foldability of relaxin family members. In contrast to the effect on insulin family activity, d-Ala or d-Ser replacement had no detrimental effect on the binding and activation potencies of the mature R3/I5 towards both RXFP3 and RXFP4, suggesting that the conserved Gly residue is irrelevant to the relaxin family’s activity. The present study revealed functionality of the conserved B-chain Gly residue for a relaxin family peptide for the first time, providing an overview of its contribution to foldability and activity of the insulin superfamily.
      PubDate: 2019-01-02
      DOI: 10.1007/s00726-018-02694-y
       
  • Nutritionally non-essential amino acids are dispensable for whole-body
           protein synthesis after exercise in endurance athletes with an adequate
           essential amino acid intake
    • Authors: Hiroyuki Kato; Kimberly A. Volterman; Daniel W. D. West; Katsuya Suzuki; Daniel R. Moore
      Pages: 1679 - 1684
      Abstract: The increased protein requirement of endurance athletes may be related to the need to replace exercise-induced oxidative losses, especially of the branched-chain amino acids (BCAA). However, it is unknown if non-essential amino acids (NEAA) influence the requirement for essential amino acids (EAA) during post-exercise recovery. Seven endurance-trained males ran 20 km prior to consuming [13C]phenylalanine, sufficient energy, and: (1) deficient protein (BASE); (2) BASE supplemented with sufficient BCAA (BCAAsup); (3) an equivalent EAA intake as BCAA (LowEAA), and; (4) sufficient EAA intake (HighEAA). [13C]Phenylalanine oxidation (the reciprocal of protein synthesis) for BCAAsup and HighEAA (0.54 ± 0.15, 0.49 ± 0.11 µmol kg−1 h−1; Mean ± SD) were significantly lower than BASE (0.74 ± 0.14 µmol kg−1 h−1; P < 0.01 for both) and LowEAA (0.70 ± 0.11 µmol kg−1 h−1; P < 0.05 and 0.01, respectively). Our results suggest that exogenous NEAA are dispensable for whole-body protein synthesis during recovery from endurance exercise provided sufficient EAA are consumed. Endurance athletes who may be at risk of not meeting their elevated protein requirements should prioritize the intake of EAA-enriched foods and/or supplements.
      PubDate: 2018-12-01
      DOI: 10.1007/s00726-018-2639-y
      Issue No: Vol. 50, No. 12 (2018)
       
  • 4-Chloro- l -kynurenine as fluorescent amino acid in natural peptides
    • Authors: Vera A. Alferova; Maxim V. Shuvalov; Taisiya A. Suchkova; Gleb V. Proskurin; Ilya O. Aparin; Eugene A. Rogozhin; Roman A. Novikov; Pavel N. Solyev; Alexey A. Chistov; Alexey V. Ustinov; Anton P. Tyurin; Vladimir A. Korshun
      Pages: 1697 - 1705
      Abstract: 4-Chloro-l-kynurenine (3-(4-chloroanthraniloyl)-l-alanine, l-4-ClKyn), an amino acid known as a prospective antidepressant, was recently for the first time found in nature in the lipopeptide antibiotic taromycin. Here, we report another instance of its identification in a natural product: 4-chloro-l-kynurenine was isolated from acidic hydrolysis of a new complex peptide antibiotic INA-5812. l-4-ClKyn is a fluorescent compound responsible for the fluorescence of the above antibiotic. Whereas fluorescence of 4-chlorokynurenine was not reported before, we synthesized the racemic compound and studied its emission in various solvents. Next, we prepared conjugates of dl-4-ClKyn with two suitable energy acceptors, BODIPY FL and 3-(phenylethynyl)perylene (PEPe), and studied fluorescence of the derivatives. 4-Chloro-dl-kynurenine emission is not detected in both conjugates, thus evidencing effective energy transfer. However, BODIPY FL emission in the conjugate is substantially reduced, probably due to collisional or photoinduced charge-transfer-mediated quenching. The intrinsic fluorescence of l-4-ClKyn amino acid in antibiotics paves the way for spectral studies of their mode of action.
      PubDate: 2018-12-01
      DOI: 10.1007/s00726-018-2642-3
      Issue No: Vol. 50, No. 12 (2018)
       
  • Mitochondrial targeting domain of NOXA causes necrosis in
           apoptosis-resistant tumor cells
    • Authors: Dai-Trang Nguyen; Siyuan He; Ji-Hye Han; Junghee Park; Young-Woo Seo; Tae-Hyoung Kim
      Pages: 1707 - 1717
      Abstract: The resistance of tumor cells to apoptosis-inducing anticancer agents is regarded as a major impediment for the treatment of cancer patients. This study aimed to examine the possibility whether a necrosis-inducing peptide containing the mitochondria-targeting domain (MTD) of NOXA kills tumor cells that are resistant to apoptosis-inducing anticancer agents. To examine this possibility, we established doxorubicin-resistant (Dox-Res) cells by treating CT26 cells with increasing amounts of doxorubicin. The apoptosis resistance of the Dox-Res CT26 cells was confirmed by measuring the cell viability and activation of caspases. We showed that the MTD-containing peptide fused to eight arginine residues (R8:MTD), a necrosis-inducing peptide, induced necrosis in the Dox-Res CT26 cells, together with a cytosolic calcium spike, reactive oxygen species production, and the release of high mobility group box 1 into the media. Moreover, we demonstrated the killing effect of R8:MTD in tumor tissues generated using the Dox-Res CT26 cells in a mouse model. Therefore, our results suggest that MTD-containing peptides may provide an alternative tool for the elimination of relapsed tumor cells that are not responsive to apoptosis-inducing anticancer agents.
      PubDate: 2018-12-01
      DOI: 10.1007/s00726-018-2644-1
      Issue No: Vol. 50, No. 12 (2018)
       
  • Dietary l -lysine supplementation altered the content of pancreatic
           polypeptide, enzymes involved in glutamine metabolism, and β-actin in
           rats
    • Authors: Chao-Wu Xiao; Caroline Faddoul; Carla Wood
      Pages: 1729 - 1737
      Abstract: This study investigated the effects of Lys supplementation on serum pancreatic polypeptide (PP), glutamine (Gln) levels and the expression of PP, Gln synthetase (GlnS), glutaminase (Gls) and β-actin in different tissues such as pancreas, skeletal muscle, liver and kidney in rats. Male Sprague–Dawley rats were fed diets containing 7% casein supplemented with either 0% (Control), 1%, 1.5%, 3% Lys or 3% Lys with 1.5% Arg for a week. All rats were necropsied for collection of blood and tissues. Expression of PP, GlnS, Gls, and β-actin in tissues were determined using Western blotting. The results showed that the rats fed 3% supplemental Lys had significantly lower body weight gain (BWG) and food intake than the ≤ 1.5% Lys groups (P < 0.05). Supplementation with ≥ 1% Lys increased serum PP level (P < 0.05), but had no significant effect on pancreatic PP abundance (P > 0.05). GlnS expression was significantly lowered in skeletal muscle by ≥ 1.5% supplemental Lys compared to the Control (P < 0.05). The expression of Gls in the kidney was increased by the addition of 1.5% Arg to 3% Lys diet (P < 0.05). Liver β-actin significantly increased with both Lys and Arg supplementation and muscle β-actin significantly decreased (P < 0.05) with ≥ 1.5% supplemental Lys. Kidney β-actin significantly increased with Arg supplementation vs 3% Lys alone (P < 0.05). These results showed that dietary supplementation with ≥ 1.5% Lys significantly suppressed GlnS expression in the skeletal muscle, which may contribute to the decreased serum Gln levels, and that increased serum PP by Lys may be due to suppressed catabolism rather than increased synthesis of PP. Lys-induced PP may play a role in reducing food intake and BWG.
      PubDate: 2018-12-01
      DOI: 10.1007/s00726-018-2648-x
      Issue No: Vol. 50, No. 12 (2018)
       
  • Taurine exhibits an apoptosis-inducing effect on human nasopharyngeal
           carcinoma cells through PTEN/Akt pathways in vitro
    • Authors: Feng He; Ning Ma; Kaoru Midorikawa; Yusuke Hiraku; Shinji Oikawa; Zhe Zhang; Guangwu Huang; Kazuhiko Takeuchi; Mariko Murata
      Pages: 1749 - 1758
      Abstract: Nasopharyngeal carcinoma (NPC) is a distinctive type of head and neck malignancy with a high incidence in southern China. Previous studies have confirmed that taurine shows an anti-cancer effect on a variety of human tumors by inhibiting cell proliferation and inducing apoptosis. However, the underlying molecular mechanism of its anti-cancer effect on NPC is not well understood. To clarify these anti-cancer mechanisms, we performed cell viability and colony formation assays. Apoptotic cells were quantified by flow cytometry. The expression levels of apoptosis-related proteins were evaluated by Western blot. The results showed that taurine markedly inhibited cell proliferation in NPC cells, but only slightly in an immortalized normal nasopharyngeal cell line. Taurine suppressed colony formation and induced apoptosis of NPC cell lines in a dose-dependent manner. Furthermore, taurine increased the active form of caspase-9/3 in a dose-dependent manner. Taurine down-regulated the anti-apoptotic protein Bcl-xL and up-regulated the pro-apoptotic protein Bax and GRP78, a major endoplasmic reticulum (ER) chaperone. These results suggest the involvement of mitochondrial and ER stress signaling in apoptosis. In addition, taurine increased the levels of PTEN (phosphatase and tensin homolog deleted on chromosome 10) and p53, and reduced phosphorylated Akt (protein kinase B). In conclusion, taurine may inhibit cell proliferation and induce apoptosis in NPC through PTEN activation with concomitant Akt inactivation.
      PubDate: 2018-12-01
      DOI: 10.1007/s00726-018-2651-2
      Issue No: Vol. 50, No. 12 (2018)
       
  • 1 H NMR spectroscopy in the presence of Mosher acid to rapidly determine
           the enantiomeric composition of amino acid benzyl esters, chirons
           susceptible to easy racemization
    • Authors: Cristiano Bolchi; Gabriella Roda; Marco Pallavicini
      Pages: 1759 - 1767
      Abstract: Amino acid benzyl esters are very useful chiral synthons, whose enantiomeric purity needs to be carefully verified because of their susceptibility to easy racemization. Alternative to chiral HPLC, 1H NMR in the presence of a chiral solvating agent (CSA) can allow a more rapid and acceptably accurate determination of the enantiomeric composition, if explicit spectral non-equivalence of one or more protons of the analyte enantiomers is found. Here, we have studied the enantiodiscrimination of 13 amino acid benzyl esters by 1H NMR in the presence of (R)-Mosher acid and in different solvents proving that, for 5 of them (Ala, Pro, Glu, Met, Ser), efficient enantiodifferentiation can be achieved and ≤ 98% enatiomeric excesses accurately determined. Generally, as expectable, the best enantiodifferentiated proton was that on the amino acid stereogenic α-carbon, but also the spectral non-equivalence of methyl protons and of protons on the β-carbon and on the benzylic carbon could be exploited to distinguish the two enantiomers and to quantify the minor one. Structural feature favoring the amino acid ester enantiodiscrimination by the CSA seems to be low sterical hindrance at the amino acid β-carbon.
      PubDate: 2018-12-01
      DOI: 10.1007/s00726-018-2653-0
      Issue No: Vol. 50, No. 12 (2018)
       
  • PGC1α regulates ACMSD expression through cooperation with HNF4α
    • Authors: Manami Koshiguchi; Shizuka Hirai; Yukari Egashira
      Pages: 1769 - 1773
      Abstract: ACMSD is a tryptophan metabolic key enzyme. HNF4α regulates the transcription of some energy-metabolic enzymes by cooperating with PGC1α, a major transcriptional co-regulator involved in energy metabolism. In this study, we investigated the involvement of PGC1α in Acmsd expression through cooperation with HNF4α. Luciferase reporter assay was performed in NIH3T3 cells using a reporter vector containing HNF4α responsive elements in the Acmsd 5′ upstream transcriptional regulatory region together with HNF4α and/or PGC1α expression vectors. The Acmsd luciferase reporter activity was greatly elevated by co-overexpression of HNF4α and PGC1α in NIH3T3 cells. Moreover, the expression level of Acmsd mRNA was significantly increased by co-overexpression of HNF4α and PGC1α in primary hepatocytes compared with expression of either HNF4α or PGC1α alone. These results indicate that PGC1α is involved in Acmsd expression through cooperation with HNF4α.
      PubDate: 2018-12-01
      DOI: 10.1007/s00726-018-2652-1
      Issue No: Vol. 50, No. 12 (2018)
       
  • Structural properties and role of the endocannabinoid lipases ABHD6 and
           ABHD12 in lipid signalling and disease
    • Authors: Laura Kind; Petri Kursula
      Abstract: The endocannabinoid (eCB) system is an important part of both the human central nervous system (CNS) and peripheral tissues. It is involved in the regulation of various physiological and neuronal processes and has been associated with various diseases. The eCB system is a complex network composed of receptor molecules, their cannabinoid ligands, and enzymes regulating the synthesis, release, uptake, and degradation of the signalling molecules. Although the eCB system and the molecular processes of eCB signalling have been studied extensively over the past decades, the involved molecules and underlying signalling mechanisms have not been described in full detail. An example pose the two poorly characterised eCB-degrading enzymes α/β-hydrolase domain protein six (ABHD6) and ABHD12, which have been shown to hydrolyse 2-arachidonoyl glycerol—the main eCB in the CNS. We review the current knowledge about the eCB system and the role of ABHD6 and ABHD12 within this important signalling system and associated diseases. Homology modelling and multiple sequence alignments highlight the structural features of the studied enzymes and their similarities, as well as the structural basis of disease-related ABHD12 mutations. However, homologies within the ABHD family are very low, and even the closest homologues have widely varying substrate preferences. Detailed experimental analyses at the molecular level will be necessary to understand these important enzymes in full detail.
      PubDate: 2018-12-18
      DOI: 10.1007/s00726-018-2682-8
       
  • Pharmacological activation of dimethylarginine dimethylaminohydrolase
           (DDAH) activity by inorganic nitrate and DDAH inhibition by N G -hydroxy-
           l -arginine, N ω , N ω -dimethyl- l -citrulline and N ω , N ω
           -dimethyl- N δ -hydroxy- l -citrulline: results and overview
    • Authors: Alexander Bollenbach; Dimitrios Tsikas
      Abstract: Asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) are endogenous inhibitors of nitric oxide (NO) synthase. SDMA is excreted in the urine without major metabolization. About 10% of daily produced ADMA are excreted unchanged in the urine. The major elimination route of ADMA (about 90%) involves its hydrolysis to dimethylamine (DMA) and l-citrulline by dimethylarginine dimethylaminohydrolase (DDAH) and excretion of DMA in the urine. High circulating and low excretory concentrations of ADMA are considered risk factors. Experimentally, DDAH activity can be inhibited by SH-specific agents such as inorganic and organic mercury compounds, and by S-nitrosothiols which block the SH group of a particular cysteine moiety of DDAH that is essential for its hydrolytic activity. Alternatively, DDAH activity can be inhibited by organic compounds that compete with the substrate ADMA for DDAH. Arginine analogs that contain substituents on guanidine nitrogen atom(s) (NG) represent a class of DDAH inhibitors. In the present study, we investigated the effects of physiological and natural amino acid derivatives of l-arginine and l-citrulline as well as of nitrate and nitrite, the major circulating and excretory metabolites of NO and NO donating drugs. Here, we report for the first time that the physiological NG-hydroxy-l-arginine, an isolable intermediate in NO synthesis, inhibits recombinant DDAH-1 activity (IC50 ≈ 100 µM). Two plant l-citrulline derivatives, i.e., Nω,Nω-dimethyl-l-citrulline and Nω,Nω-dimethyl-Nδ-hydroxy-l-citrulline (connatin), were found to inhibit almost completely hepatic DDAH activity in vitro in rat homogenate at a concentration of 100 µM each. At pharmacological concentrations (i.e., 1 mM), inorganic nitrate, but not inorganic nitrite, was found to increase rat liver DDAH activity. In urine of 18 patients with Becker’s muscular dystrophy, nitrate was found to correlate closely with DMA (Spearman, r = 0.73, p = 0.002). In summary, NG-hydroxy-l-arginine, Nω,Nω-dimethyl-l-citrulline and Nω,Nω-dimethyl-Nδ-hydroxy-l-citrulline are novel inhibitors of DDAH activity. This article provides an overview of amino acid-based DDAH inhibitors and discusses potential underlying inhibition mechanisms.
      PubDate: 2018-12-08
      DOI: 10.1007/s00726-018-2684-6
       
  • The first comprehensive description of the expression profile of genes
           involved in differential body growth and the immune system of the Jeju
           Native Pig and miniature pig
    • Authors: Mrinmoy Ghosh; Neelesh Sharma; Meeta Gera; Nameun Kim; Simrinder Singh Sodhi; KrishnaKanth Pulicherla; Do Huynh; Dae Cheol Kim; Jiaojiao Zhang; Taeho Kwon; Kyung Tak Do; Hak Kyo Lee; Ki-Duk Song; DongKee Jeong
      Abstract: Sus scrofa provides a major source of animal protein for humans as well as being an excellent biomedical model. This study was carried out to understand, in detail, the genetic and functional variants of Jeju Native Pigs and miniature pigs through differential expression profiling of the genes controlling their immune response, growth performance, and meat quality. The Illumina HiSeq 2000 platform was used for generating 1.3 billion 90 bp paired-end reads, which were mapped to the S. scrofa genome using TopHat2. A total of 2481 and 2768 genes were differentially expressed with 8-log changes in muscle and liver samples, respectively. Five hundred forty-eight genes in muscle and 642 genes in liver samples had BLAST matches within the non-redundant database. GO process and pathway analyses showed enhanced biological processes related to the extracellular structural organization and skeletal muscle cell differentiation in muscle tissue, whereas the liver tissue shares functions related to the inflammatory response. Herein, we identify inflammatory regulatory genes in miniature pigs and growth response genes in Jeju Native Pigs, information which can provide a stronger base for the selection of breeding stock and facilitate further in vitro and in vivo studies for therapeutic purposes.
      PubDate: 2018-12-05
      DOI: 10.1007/s00726-018-2685-5
       
  • Globular protein backbone conformational disorder in crystal structures
    • Authors: Oliviero Carugo
      Abstract: Proteins are not static molecules but dynamic entities able to modify their structure for several reasons, from the necessity to recognize partners to the regulation of their thermodynamic stability. Conformational disorder is frequent in protein structures and atoms can have, in protein crystal structures, two or more alternative, equilibrium positions close to each other. Here, a set of protein crystal structures refined at very high resolution (1 Å or better) is examined to characterize the conformational disorder of the backbone atoms, which is not infrequent: about 15% of the protein backbone atoms are conformationally disordered and three quarters of them have been deposited with two or more equilibrium positions (most of the others were not detected in the electron density maps). Several structural features have been examined and it was observed that Cα atoms tend to be disordered more frequently than the other backbone atoms, likely because their disorder is induced by disordered side chains: side-chain disorder is two times more frequent than backbone disorder. Surprisingly, backbone disorder is only slightly more frequent in loops than in helices and strands and this is in agreement with the observation that backbone disorder is a localized phenomenon: in about 80% of the cases, it is observed in one amino acid and not in its neighbors. However, although backbone disorder does not cluster along the polypeptide sequence, it tends to cluster in 3D, since backbone-disordered amino acids distant in sequence are close in the 3D space.
      PubDate: 2018-12-04
      DOI: 10.1007/s00726-018-2683-7
       
 
 
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