scholarly journals Aromatic Amino Acid Decarboxylase Deficiency: The Added Value of Biochemistry

2021 ◽  
Vol 22 (6) ◽  
pp. 3146
Author(s):  
Riccardo Montioli ◽  
Carla Borri Voltattorni

Aromatic amino acid decarboxylase (AADC) deficiency is a rare, autosomal recessive neurometabolic disorder caused by mutations in the DDC gene, leading to a deficit of AADC, a pyridoxal 5′-phosphate requiring enzyme that catalyzes the decarboxylation of L-Dopa and L-5-hydroxytryptophan in dopamine and serotonin, respectively. Although clinical and genetic studies have given the major contribution to the diagnosis and therapy of AADC deficiency, biochemical investigations have also helped the comprehension of this disorder at a molecular level. Here, we reported the steps leading to the elucidation of the functional and structural features of the enzyme that were useful to identify the different molecular defects caused by the mutations, either in homozygosis or in heterozygosis, associated with AADC deficiency. By revisiting the biochemical data available on the characterization of the pathogenic variants in the purified recombinant form, and interpreting them on the basis of the structure-function relationship of AADC, it was possible: (i) to define the enzymatic phenotype of patients harboring pathogenic mutations and at the same time to propose specific therapeutic managements, and (ii) to identify residues and/or regions of the enzyme relevant for catalysis and/or folding of AADC.

Life Sciences ◽  
1982 ◽  
Vol 31 (14) ◽  
pp. 1519-1524 ◽  
Author(s):  
Erminia Barboni ◽  
Carla Borri Voltattorni ◽  
Maria D'Erme ◽  
Anna Fiori ◽  
Alba Minelli ◽  
...  

Pteridines ◽  
1997 ◽  
Vol 8 (3) ◽  
pp. 206-210
Author(s):  
Hideo Sakamoto ◽  
Ko Fujita ◽  
Hiroshi Kuzuya

Summary Based on the hypothesis that catecholamine decreases may cause increases in biopterin, we measured the GTP cyclohydrolase I(GTPCH-I) activity and biopterin content in the cerebral cortex, midbrain/diencephalon, cerebeilum, pons/medulla oblongata, striatum , and hippocampus of brains from rats given NSDlOIS, an inhibitor for aromatic amino acid decarboxylase . The catecholamine contents decreased in all the regions tested. The changes in the GTPCH -I activity and bioptcrin content were different among the regions; they decreased in some regions contrary to expectations and increased in other regions. However, either the enzyme activity or biopterin content increased in the midbrain/ diencephalon and pons/ medulla oblongata, in which similar levels of catecholamines, GTPCH -I activity and biopterin were detected. These results suggest that for the midbrain/diencephalon and pons/medulla oblongata the surmise that a decrease in catecholamines causes an increase in the biopterin synthesis may be correct.


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