Disease relevance of DDC

• DDC has been implicated in a number of clinic disorders, including Parkinson's disease and hypertension [1].
• Pig kidney dopa decarboxylase (DDC) expressed in Escherichia coli is a homodimeric enzyme containing one catalytically active pyridoxal 5'-phosphate active site per subunit [2].
• Characterization of DOPA decarboxylase mRNA in rat pheochromocytoma [3].

High impact information on DDC

• DOPA decarboxylase (DDC) is responsible for the synthesis of the key neurotransmitters dopamine and serotonin via decarboxylation of L-3,4-dihydroxyphenylalanine (L-DOPA) and L-5-hydroxytryptophan, respectively [1].
• Another 50% of the nerve cell bodies contained immunoreactivity (IR) to dopamine-beta-hydroxylase (DBH), but did not have any other characteristics of noradrenergic neurons; they did not contain detectable catecholamines, or IR to dopa decarboxylase (DDC) or tyrosine (TH) hydroxylase, nor did they take up exogenous catecholamines [4].
• Concurrent with this reaction, 5-HT inactivates DDC in both a time- and concentration-dependent manner and exhibits saturation of the rate of inactivation at high concentrations, with Ki and Kinact values of 0.40 mM and 0.023 min-1, respectively [2].
• Taken together, these findings indicate that recombinant pig kidney DDC has two active-site PLP molecules and therefore displays structural characteristics typical of PLP-dependent homodimeric enzymes [5].
• All these data, besides validating the functional DDC active site model, represent an important step toward the elucidation of the catalytic pathway of oxidative deamination [6].

Biological context of DDC

• L-Aromatic amino acid decarboxylase (dopa decarboxylase; DDC) is a pyridoxal 5'-phosphate (PLP)-dependent homodimeric enzyme that catalyses the decarboxylation of L-dopa and other L-aromatic amino acids [5].
• Some structural elements relevant for the control of reaction and substrate specificity of DDC have been identified by means of limited tryptic digestion and site-directed mutagenesis studies [7].
• A DOPA decarboxylase inhibitor in clinical use, benserazide, is, however, a much superior catechol-O-methyltransferase substrate and may have the therapeutic advantage of decreasing methylation of L-DOPA [2] [8].
• We used compartmental kinetics to test the hypothesis that utilization of the DOPA decarboxylase substrate [(18)F]fluorodopa is potentiated in living striatum following acute treatment with a typical neuroleptic [9].
• The activity of the enzyme is expressed as the rate of the TH-catalysed tyrosine hydroxylation to 3,4-dihydroxyphenyl-alanine (DOPA) using tritium-labeled tyrosine, in the presence of cofactors and a DOPA decarboxylase inhibitor [10].

Anatomical context of DDC

• Contrary to expectation, co-grafting of transfected GDNF-expressing HiB5 cells, a rat-derived neural cell line, tended to impair the survival of the grafts with the lowest values for graft volumes, TH-positive cell numbers, behavioral scores, and relative DOPA decarboxylase activity [11].

Associations of DDC with chemical compounds

• Cysteine 111 in Dopa decarboxylase (DDC) has been replaced by alanine or serine by site-directed mutagenesis [12].
• In contrast, gallic acid behaves as a weak inhibitor of DDC [13].
• Dopa decarboxylase (DDC) catalyzes as main reaction the stereospecific CO(2) abstraction from L-Dopa and L-5-hydroxytryptophan (5-HTP), generating the corresponding aromatic amines, dopamine and serotonin, respectively [7].
• Mutation of cysteine 111 in Dopa decarboxylase leads to active site perturbation [12].
• The reactions of Dopa decarboxylase (DDC) with l- and d-enantiomers of tryptophan methyl ester are described [6].

Analytical, diagnostic and therapeutic context of DDC

• Crystallization and preliminary X-ray analysis of pig kidney DOPA decarboxylase [14].
• Benserazide, an inhibitor of dopa-decarboxylase, completely prevented the reduction in isoproterenol-induced relaxation after H. influenzae vaccination, while no effect on relaxation of tracheal spirals from control animals was detected [15].
• Dopa decarboxylase from pig kidney is a pyridoxal-5'-phosphate (PLP) dependent enzyme that displays positive circular dichroism (CD) relative to the coenzyme absorption bands at 335 and 420 nm, which are characteristic of an asymmetrically bound coenzyme [16].
• 3. A DOPA decarboxylase and a p-tyrosine decarboxylase were separated by gel filtration and ion exchange chromatography [17].

References