caa a22 4500 475785630 CHVBK 20180406123657.0 cr unu---uuuuu 170329e20000901xx s 000 0 eng 10.1007/PL00014370 doi (NATIONALLICENCE)springer-10.1007/PL00014370 The neurochemistry of phenylketonuria [Elektronische Daten] [Robert Surtees, Nenad Blau] The mechanisms by which deficiency of hepatic phenylalanine hydroxylase causes central nervous system disease are reviewed. The neurological disease appears to be secondary to increased concentrations of phenylalanine and a decrease in the concentrations of other large neutral amino acids, especially methionine and tyrosine, within the central nervous system. This causes a deficiency of the neurotransmitter dopamine, reduced protein synthesis and demyelination. Similar mechanisms appear to be operating when blood phenylalanine concentrations are in the range expected for early continuously treated phenylketonuria. Conclusion The severe brain disease found in phenylketonuria is caused by a raised blood phenylalanine content which increases the brain free phenylalanine and decreases the concentration of other large neutral amino acids. Brain protein synthesis is decreased, myelin turnover is increased and there are abnormalities in amine neurotransmitter systems. Springer-Verlag Berlin Heidelberg, 2000 Key words Phenylalanine hydroxylase deficiency nationallicence Hyperphenylalaninaemia nationallicence Neurotransmitters nationallicence Demyelination nationallicence Central nervous system nationallicence AbbreviationsBH4 tetrahydrobiopterin nationallicence GTP guanosine triphosphate nationallicence GFRP GTPCH feed-back regulatory protein nationallicence GTPCH GTP cyclohydrolase I nationallicence HPA hyperphenylalaninaemia nationallicence PAH phenylalanine 4-hydroxylase nationallicence Phe phenylalanine nationallicence PKU phenylketonuria nationallicence PTPS 6-pyruvoyltetrahydropterin synthase nationallicence SR sepiapterin reductase nationallicence Surtees Robert Institute of Child Health (UCLMS), 30, Guilford Street, London WC1N 1EH, UK e-mail: r.surtees@ich.ucl.ac.uk Tel.: +44-20-7837-7618; Fax: +44-20-7833-7618, GB aut Blau Nenad University Children's Hospital, Steinwiesstrasse 75, 8032 Zurich, Switzerland, CH aut https://doi.org/10.1007/PL00014370 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/PL00014370 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Surtees Robert Institute of Child Health (UCLMS), 30, Guilford Street, London WC1N 1EH, UK e-mail: r.surtees@ich.ucl.ac.uk Tel.: +44-20-7837-7618; Fax: +44-20-7833-7618, GB aut NATIONALLICENCE 700 1- Blau Nenad University Children's Hospital, Steinwiesstrasse 75, 8032 Zurich, Switzerland, CH aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer