Disease relevance of DDC

• When 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) is given to animals, it produces a hepatic porphyria resembling human variegate porphyria thus providing an experimental system in which to study this disease [1].
• Aromatic L-amino acid decarboxylase (AADC) was purified from bovine adrenal medulla and properties of this enzyme were compared with those of AADC from human pheochromocytoma [2].

High impact information on DDC

• Aromatic L-amino acid decarboxylase was purified to electrophoretic homogeneity from bovine adrenal medulla, and highly specific antibodies were produced [3].
• Moreover, cotransfection of TH with AADC genes was readily accomplished by this procedure and resulted in a greater and longer-lasting improvement of apomorphine-induced rotational behavior than was achieved by transfection of TH gene alone [4].
• Lack of regulation of aromatic L-amino acid decarboxylase in intact bovine chromaffin cells [5].
• In the present study, the phosphorylation and activity of AADC was evaluated relative to that of tyrosine hydroxylase (TH; the first and rate-limiting enzyme in the pathway) in intact bovine chromaffin cells [5].
• Under the same conditions, we found no variation in either the activities of other catecholamine biosynthetic enzymes (dopamine beta-hydroxylase and DOPA decarboxylase), or in metabolic enzymes such as lactate dehydrogenase and cytochrome c oxidase, and a decrease in the cellular content of chromogranin A and cytochrome b-561 [6].

Biological context of DDC

• Deduced amino acid sequence of bovine aromatic L-amino acid decarboxylase: homology to other decarboxylases [7].
• The 7-amino acid sequence of the pyridoxal phosphate binding site is completely conserved among drosophila, pig and bovine AADC [7].
• Nucleotide sequence of cDNA for bovine aromatic L-amino acid decarboxylase (AADC) was analyzed [7].

Anatomical context of DDC

• These results suggest that DDC inhibits preferentially progenitor cells from CMLBM [8].
• Expression of cloned aromatic L-amino acid decarboxylase in Xenopus laevis oocytes [9].

Associations of DDC with chemical compounds

• The ferrochelatase inhibitor 3,5-diethoxycarbonyl-1,4-dihydro-2,4,6-trimethylpyridine (DDC) blocked the stimulation of aldosterone mediated by adrenocorticotropin (ACTH) [10].
• Metabolic conversion of L-dopa by AADC is thus preserved in the case of an approach via the basolateral side of the proximal tubular cells [11].
• Gamma-L-glutamyl-L-dopa (or gludopa), a dopamine (DA) prodrug, is selectively metabolized in vivo by the kidney through the sequential action of two renal enzymes, gamma-glutamyl transpeptidase (gamma-GT) and aromatic L-amino acid decarboxylase (AADC) [11].
• The accumulation rate of 3,4-dihydroxyphenylalanine (DOPA) in vivo in the retina of diabetic rats, measured following the administration of the AADC inhibitor m-hydroxybenzyl-hydrazine (100 mg/kg i.p.), was also unchanged [12].
• The expressed enzyme activity was stereoselective for L-5-hydroxytryptophan and L-DOPA and blocked by NSD-1015 an inhibitor of AADC [9].

Other interactions of DDC

• Tyrosine hydroxylase activity was assayed by measuring 3,4-dihydroxyphenylalanine (Dopa) accumulation in the presence of brocresine, an inhibitor of Dopa decarboxylase [13].

Analytical, diagnostic and therapeutic context of DDC

• Addition of hemin after treatment with DDC partially restored ACTH action [10].
• Furthermore, Southern blot analysis reveals that a single gene codes for aromatic L-amino acid decarboxylase [3].
• Aromatic L-amino acid decarboxylase was purified from bovine brain for the first time by affinity chromatography using a monoclonal antibody to the enzyme, and it was compared with the decarboxylase purified from bovine adrenal medulla by the same procedure [14].
• Activity of these neurons was estimated by measuring the accumulation of dihydroxyphenylalanine, the immediate precursor of dopamine, 15 min after an intravenous injection of the aromatic L-amino acid decarboxylase inhibitor, 3-hydroxybenzylhydrazine [15].
• Sense mRNA coding for bovine adrenal medulla aromatic L-amino acid decarboxylase (AADC) was expressed following microinjection into Xenopus laevis oocytes [9].

References