کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2000315 1541570 2007 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Aromatic l-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Aromatic l-amino acid decarboxylase enzyme activity in deficient patients and heterozygotes
چکیده انگلیسی

BackgroundAromatic l-amino acid decarboxylase (AADC) deficiency is a rare autosomal recessive disorder characterised by developmental delay, motor retardation and autonomic dysfunction. Very low concentrations in cerebrospinal fluid (CSF) of homovanillic acid (HVA) and 5-hydroxy indole acetic acid (5-HIAA) are suggestive, but not specific, for this disorder. Confirmation of the diagnosis AADC deficiency is then required by enzyme activity measurement or genetic analysis.MethodsWe describe assays for plasma AADC enzyme activity using both of its substrates, 5-hydroxytryptophan (5-HTP) and 3,4-dihydroxyphenylalanine (l-dopa). We measured AADC activity in controls, AADC deficient patients and heterozygotes.ResultsAADC enzyme activity in control plasma on average is a factor 8–12 higher with l-dopa as substrate than with 5-HTP. Both substrates of AADC compete for the same active site of the enzyme resulting in equally decreased residual enzyme activities in AADC deficient patients. In AADC deficient patients, the enzyme activity towards both substrates, l-dopa and 5-HTP, are equally decreased, as are the CSF concentrations of HVA, 5-HIAA and MHPG, whereas heterozygotes have intermediate AADC activity levels.ConclusionsThe presently described assays for AADC activity measurement allow an efficient, reproducible and non-invasive way to confirm the diagnosis of AADC deficiency. Since AADC enzyme activity is much higher with l-dopa as a substrate, this method is to be preferred over activity measurement with 5-HTP as a substrate for diagnostic purposes.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular Genetics and Metabolism - Volume 90, Issue 4, April 2007, Pages 363–369
نویسندگان
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