| Pyridoxal 5'-phosphate deficiency causes a loss of aromatic L-amino acid decarboxylase in patients and human neuroblastoma cells, implications for aromatic L-amino acid decarboxylase and vitamin B(6) deficiency states. | |
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MedLine Citation:
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PMID: 20403077 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Pyridoxal 5'-phosphate, the active form of vitamin B(6), is an essential cofactor for multiple enzymes, including aromatic l-amino acid decarboxylase that catalyses the final stage in the production of the neurotransmitters dopamine and serotonin. In two patients with inherited disorders of vitamin B(6) metabolism, we observed reductions in plasma aromatic l-amino acid decarboxylase activity. In one patient, this change was related to an increase in K(m) for pyridoxal 5'-phosphate. Furthermore, pyridoxal 5'-phosphate-deficient human SH-SY5Y neuroblastoma cells were found to exhibit reduced levels of aromatic l-amino acid decarboxylase activity and protein but with no alteration in expression. Further reductions in activity and protein were observed with the addition of the vitamin B(6) antagonist 4-deoxypyridoxine, which also reduced aromatic l-amino acid decarboxylase mRNA levels. Neither pyridoxal 5'-phosphate deficiency nor the addition of 4-deoxypyridoxine affected aromatic l-amino acid decarboxylase stability over 8 h with protein synthesis inhibited. Increasing extracellular availability of pyridoxal 5'-phosphate was not found to have any significant effect on intracellular pyridoxal 5'-phosphate concentrations or on aromatic l-amino acid decarboxylase. These findings suggest that maintaining adequate pyridoxal 5'-phosphate availability may be important for optimal treatment of aromatic l-amino acid decarboxylase deficiency and l-dopa-responsive conditions. |
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Authors:
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George F G Allen; Viruna Neergheen; Marcus Oppenheim; Julia C Fitzgerald; Emma Footitt; Keith Hyland; Peter T Clayton; John M Land; Simon J R Heales |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-04-09 |
Journal Detail:
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Title: Journal of neurochemistry Volume: 114 ISSN: 1471-4159 ISO Abbreviation: J. Neurochem. Publication Date: 2010 Jul |
Date Detail:
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Created Date: 2010-07-05 Completed Date: 2010-07-19 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985190R Medline TA: J Neurochem Country: England |
Other Details:
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Languages: eng Pagination: 87-96 Citation Subset: IM |
Affiliation:
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Department of Molecular Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK. gallen@ion.ucl.ac.uk |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aromatic-L-Amino-Acid Decarboxylases
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deficiency,
genetics,
metabolism* Cell Line, Tumor Child Enzyme Stability Humans Kinetics Pyridoxal Phosphate / deficiency* RNA, Messenger / metabolism Vitamin B 6 Deficiency / metabolism* |
| Chemical | |
Reg. No./Substance:
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0/RNA, Messenger; 54-47-7/Pyridoxal Phosphate; EC 4.1.1.28/Aromatic-L-Amino-Acid Decarboxylases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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