Original title: Charakterizace rekombinantní lidské serinracemasy
Translated title: Characterization of recombinant human serine racemase
Authors: Hoffman, Hillary Elizabeth ; Konvalinka, Jan (advisor) ; Křen, Vladimír (referee) ; Čeřovská, Noemi (referee)
Document type: Doctoral theses
Year: 2010
Language: eng
Abstract: 6 Brief Abstract The pyridoxal-5'-phosphate-dependent enzyme serine racemase (SR) is responsible for the biosynthesis of D-serine in the mammalian central nervous system. D-serine acts as a neurotransmitter and coagonist, together with L-glutamate, of ionotropic N-methyl-D-aspartate receptors (NMDARs). Excitotoxic D-serine levels have been implicated in neuropathologies including Alzheimer's disease and amyotrophic lateral sclerosis. SR inhibitors offer a novel and potentially highly specific approach for attenuation of NMDAR-mediated glutamate excitotoxicity and for further study of the pathway. Many of the SR inhibitors described to date are small, naturally occurring compounds, and novel structures capable of influencing SR's activity are highly sought after. Moreover, structural information about this enigmatic enzyme is lacking, and suitable animal models need to be identified for inhibitor studies. This thesis presents the first published biochemical comparison of mouse and human SR orthologs, validating, at least in part, the use of mouse models in SR research. Additionally, hydroxamic acids are introduced as a novel class of SR inhibitors. While the experimentally determined structure of a mammalian SR remains elusive, random and site-directed mutagenesis experiments in combination with multiple...

Institution: Charles University Faculties (theses) (web)
Document availability information: Available in the Charles University Digital Repository.
Original record: http://hdl.handle.net/20.500.11956/23596

Permalink: http://www.nusl.cz/ntk/nusl-295438


The record appears in these collections:
Universities and colleges > Public universities > Charles University > Charles University Faculties (theses)
Academic theses (ETDs) > Doctoral theses
 Record created 2017-04-25, last modified 2022-03-04


No fulltext
  • Export as DC, NUŠL, RIS
  • Share