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Gene Review

DDC  -  dopa decarboxylase (aromatic L-amino acid...

Homo sapiens

Synonyms: AADC, Aromatic-L-amino-acid decarboxylase, DOPA decarboxylase
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Disease relevance of DDC


Psychiatry related information on DDC

  • Because the mesolimbic dopaminergic system is implicated in the reinforcing effects of many drugs, including nicotine, the DDC gene is considered a plausible candidate for involvement in the development of vulnerability to nicotine dependence (ND) [5].
  • Thus, our results do not support an involvement of the 1-bp or 4-bp deletion within the DDC gene in the etiology of affective disorders [6].
  • No association between polymorphisms in the DDC gene and paranoid schizophrenia in a northern Chinese population [7].
  • Application of juvenile hormone I showed that the critical period for determination of the level of the later increase in DDC activity was about 4 hr after head capsule slippage at the peak of the ecdysteroid titer [8].
  • Dopa-decarboxylase, acetylcholinesterase, sodium plus potassium stimulated adenosine triphosphatase (Na+ + K+-ATPase), and membrane-bound protein kinase were compared in the erythrocytes of patients with Huntington's disease and normal controls [9].

High impact information on DDC


Chemical compound and disease context of DDC


Biological context of DDC

  • Western blotting analysis showed a cross-reaction between anti-HDC and anti-DDC antibodies [1].
  • Haplotype analysis indicates an association between the DOPA decarboxylase (DDC) gene and nicotine dependence [5].
  • The present study investigated two Danish families for linkage between manic depressive illness, a marker at the DDC locus which has been mapped to 7p11-p13 and 10 microsatellite markers covering chromosome 7q11-p15 [19].
  • Our results demonstrate the detection of a new alternative splicing event within the coding region of the human DDC mRNA, further suggesting that the single copy human DDC gene undergoes complex processing leading to the formation of multiple mRNA isoforms [20].
  • In this report, we describe a novel splice variant of DDC mRNA in human tissue, lacking exons 10-15 of the full-length transcript but including an alternative exon 10 [20].

Anatomical context of DDC


Associations of DDC with chemical compounds


Physical interactions of DDC


Regulatory relationships of DDC

  • In addition, dual immunofluorescence analysis revealed that approximately 55% of the mixed population of DDC- and chromogranin A-expressing NE cells continue to express AR [30].
  • This suggests that in the early stage of nigrostriatal dopamine neurone degeneration, DDC levels may be less susceptible to neurodegenerative influences than is TH synthesis or, alternatively, DDC synthesis may be more aggressively upregulated [31].
  • Glucocorticoid receptor activity was also strongly enhanced with DDC co-transfection, while oestrogen receptor activity was only mildly affected [18].
  • As previously reported for lymphoid DC, DDC expressed tumour necrosis factor receptort (TNFR) 75000 MW (mAb utr-1; hTNFR-M1; and MR2-1) but lacked TNFR 55000 MW (mAb htr-9; MR1-1; and MR1-2) [32].
  • LC and DDC migrated as mature/activated APC able to stimulate allogeneic naive CD4+ T cells and to induce memory Th1 cells in the absence of IL-12p70 [33].

Other interactions of DDC

  • Immunostaining showed that TH and AADC were coexpressed efficiently in the same striatal cells in vitro and in vivo [26].
  • The assays of activities and function of TH, AADC, and GCH1 and their potential use in ex vivo gene therapy of PD [34].
  • Western blotting analysis was performed to verify the specificity of anti-DDC and anti-HDC antibodies [1].
  • The increased mRNA levels of TH and AADC were maintained at 48 h, whereas the level of DBH mRNA was sharply decreased at 48 h [35].
  • DDC demonstrated a low level of selectivity as an inhibitory probe for chlorzoxazone 6-hydroxylation (CYP2E1-mediated) [36].

Analytical, diagnostic and therapeutic context of DDC

  • Real-time RT-PCR was performed using specific probes for HDC and DDC on 42 cases, examined also for DDC IR [1].
  • These results suggest that GCH, in addition to TH and AADC, is important for effective gene therapy of PD [37].
  • We examined the distribution of striatal D-neurons using AADC immunohistochemistry and postmortem brains obtained by legal and pathological autopsies (nine controls (27-75 years old) and nine schizophrenics (32-78 years old), postmortem interval to fixation (PMI): 2-30 h) [38].
  • In this study we show the expression of DDC in human placental tissue and present data on the molecular cloning and in vitro expression of the active recombinant enzyme [39].
  • Northern blot analysis indicated that the alt-DDC transcript is expressed in high levels in human kidney [20].


  1. Histidine decarboxylase, DOPA decarboxylase, and vesicular monoamine transporter 2 expression in neuroendocrine tumors: immunohistochemical study and gene expression analysis. Uccella, S., Cerutti, R., Vigetti, D., Furlan, D., Oldrini, R., Carnevali, I., Pelosi, G., La Rosa, S., Passi, A., Capella, C. J. Histochem. Cytochem. (2006) [Pubmed]
  2. Phenylethanolamine N-methyltransferase and other enzymes of catecholamine metabolism in human brain. Nagatsu, T., Kato, T., Numata, Y., Ikuta, K., Sano, M. Clin. Chim. Acta (1977) [Pubmed]
  3. Expression of mRNA coding for four catecholamine-synthesizing enzymes in human adrenal pheochromocytomas. Isobe, K., Nakai, T., Yukimasa, N., Nanmoku, T., Takekoshi, K., Nomura, F. Eur. J. Endocrinol. (1998) [Pubmed]
  4. Adeno-associated virus vector-mediated triple gene transfer of dopamine synthetic enzymes. Fan, D., Shen, Y., Kang, D., Nakano, I., Ozawa, K. Chin. Med. J. (2001) [Pubmed]
  5. Haplotype analysis indicates an association between the DOPA decarboxylase (DDC) gene and nicotine dependence. Ma, J.Z., Beuten, J., Payne, T.J., Dupont, R.T., Elston, R.C., Li, M.D. Hum. Mol. Genet. (2005) [Pubmed]
  6. Association study between two variants in the DOPA decarboxylase gene in bipolar and unipolar affective disorder. Jahnes, E., Müller, D.J., Schulze, T.G., Windemuth, C., Cichon, S., Ohlraun, S., Fangerau, H., Held, T., Maier, W., Propping, P., Nöthen, M.M., Rietschel, M. Am. J. Med. Genet. (2002) [Pubmed]
  7. No association between polymorphisms in the DDC gene and paranoid schizophrenia in a northern Chinese population. Zhang, B., Jia, Y., Yuan, Y., Yu, X., Xu, Q., Shen, Y., Shen, Y. Psychiatr. Genet. (2004) [Pubmed]
  8. Hormonal regulation of dopa decarboxylase during a larval molt. Hiruma, K., Riddiford, L.M. Dev. Biol. (1985) [Pubmed]
  9. Increased sodium plus potassium adenosine triphosphatase activity in erythrocyte membranes in Huntington's disease. Butterfield, D.A., Oeswein, J.Q., Prunty, M.E., Hisle, K.C., Markesbery, W.R. Ann. Neurol. (1978) [Pubmed]
  10. Presynaptic dopaminergic deficits in Lesch-Nyhan disease. Ernst, M., Zametkin, A.J., Matochik, J.A., Pascualvaca, D., Jons, P.H., Hardy, K., Hankerson, J.G., Doudet, D.J., Cohen, R.M. N. Engl. J. Med. (1996) [Pubmed]
  11. Treatment of parkinson's disease with bromocriptine. Lieberman, A., Kupersmith, M., Estey, E., Goldstein, M. N. Engl. J. Med. (1976) [Pubmed]
  12. Striatal dopamine nerve terminal markers in human, chronic methamphetamine users. Wilson, J.M., Kalasinsky, K.S., Levey, A.I., Bergeron, C., Reiber, G., Anthony, R.M., Schmunk, G.A., Shannak, K., Haycock, J.W., Kish, S.J. Nat. Med. (1996) [Pubmed]
  13. Characterization of human neuroblastoma cell lines established before and after therapy. Reynolds, C.P., Biedler, J.L., Spengler, B.A., Reynolds, D.A., Ross, R.A., Frenkel, E.P., Smith, R.G. J. Natl. Cancer Inst. (1986) [Pubmed]
  14. Treatment of cirrhotic hepatic encephalopathy with L-dopa. A controlled trial. Michel, H., Solere, M., Granier, P., Cauvet, G., Bali, J.P., Pons, F., Bellet-Hermann, H. Gastroenterology (1980) [Pubmed]
  15. Molecular detection of dopamine decarboxylase expression by means of reverse transcriptase and polymerase chain reaction in bone marrow and peripheral blood: utility as a tumor marker for neuroblastoma. Bozzi, F., Luksch, R., Collini, P., Gambirasio, F., Barzanò, E., Polastri, D., Podda, M., Brando, B., Fossati-Bellani, F. Diagn. Mol. Pathol. (2004) [Pubmed]
  16. The effect of catechol-O-methyltransferase inhibition with entacapone on cardiovascular autonomic responses in L-Dopa-treated patients with Parkinson's disease. Lyytinen, J., Sovijärvi, A., Kaakkola, S., Gordin, A., Teräväinen, H. Clinical neuropharmacology. (2001) [Pubmed]
  17. Entacapone. A review of its use in Parkinson's disease. Holm, K.J., Spencer, C.M. Drugs (1999) [Pubmed]
  18. Isolation and identification of L-dopa decarboxylase as a protein that binds to and enhances transcriptional activity of the androgen receptor using the repressed transactivator yeast two-hybrid system. Wafa, L.A., Cheng, H., Rao, M.A., Nelson, C.C., Cox, M., Hirst, M., Sadowski, I., Rennie, P.S. Biochem. J. (2003) [Pubmed]
  19. No evidence of linkage between manic depressive illness and the dopa decarboxylase gene or nearby region on chromosome 7p. Ewald, H., Mors, O., Eiberg, H., Flint, T., Kruse, T.A. Psychiatr. Genet. (1995) [Pubmed]
  20. Identification and characterization of a novel form of the human L-dopa decarboxylase mRNA. Vassilacopoulou, D., Sideris, D.C., Vassiliou, A.G., Fragoulis, E.G. Neurochem. Res. (2004) [Pubmed]
  21. Catechol-O-methyltransferase and aromatic L-amino acid decarboxylase activities in human gastrointestinal tissues. Schultz, E. Life Sci. (1991) [Pubmed]
  22. L-dopa as substrate for human duodenal catechol-O-methyltransferase and aromatic L-amino acid decarboxylase. Schultz, E. Biomed. Chromatogr. (1990) [Pubmed]
  23. Peptide amidating activity in human bronchoalveolar lavage fluid. Scott, F.M., Treston, A.M., Shaw, G.L., Avis, I., Sorenson, J., Kelly, K., Dempsey, E.C., Cantor, A.B., Tockman, M., Mulshine, J.L. Lung Cancer (1996) [Pubmed]
  24. Identification of human hepatic cytochrome P450 sources of N-alkylprotoporphyrin IX after interaction with porphyrinogenic xenobiotics, implications for detection of xenobiotic-induced porphyria in humans. Lavigne, J.A., Nakatsu, K., Marks, G.S. Drug Metab. Dispos. (2002) [Pubmed]
  25. Demonstration of L-dopa decarboxylating neurons specific to human striatum. Ikemoto, K., Kitahama, K., Jouvet, A., Arai, R., Nishimura, A., Nishi, K., Nagatsu, I. Neurosci. Lett. (1997) [Pubmed]
  26. Behavioral recovery in 6-hydroxydopamine-lesioned rats by cotransduction of striatum with tyrosine hydroxylase and aromatic L-amino acid decarboxylase genes using two separate adeno-associated virus vectors. Fan, D.S., Ogawa, M., Fujimoto, K.I., Ikeguchi, K., Ogasawara, Y., Urabe, M., Nishizawa, M., Nakano, I., Yoshida, M., Nagatsu, I., Ichinose, H., Nagatsu, T., Kurtzman, G.J., Ozawa, K. Hum. Gene Ther. (1998) [Pubmed]
  27. Tyrosine hydroxylase and aromatic L-amino acid decarboxylase do not coexist in neurons in the human anterior cingulate cortex. Ikemoto, K., Kitahama, K., Nishimura, A., Jouvet, A., Nishi, K., Arai, R., Jouvet, M., Nagatsu, I. Neurosci. Lett. (1999) [Pubmed]
  28. Three Types of Tyrosine Hydroxylase-Positive CNS Neurons Distinguished by Dopa Decarboxylase and VMAT2 Co-Expression. Weihe, E., Depboylu, C., Sch??tz, B., Sch??fer, M.K., Eiden, L.E. Cell. Mol. Neurobiol. (2006) [Pubmed]
  29. Winged helix hepatocyte nuclear factor 3 and POU-domain protein brn-2/N-oct-3 bind overlapping sites on the neuronal promoter of human aromatic L-amino acid decarboxylase gene. Raynal, J.F., Dugast, C., Le Van Thaï, A., Weber, M.J. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  30. Comprehensive expression analysis of l-dopa decarboxylase and established neuroendocrine markers in neoadjuvant hormone-treated versus varying Gleason grade prostate tumors. Wafa, L.A., Palmer, J., Fazli, L., Hurtado-Coll, A., Bell, R.H., Nelson, C.C., Gleave, M.E., Cox, M.E., Rennie, P.S. Hum. Pathol. (2007) [Pubmed]
  31. Striatal dihydroxyphenylalanine decarboxylase and tyrosine hydroxylase protein in idiopathic Parkinson's disease and dominantly inherited olivopontocerebellar atrophy. Zhong, X.H., Haycock, J.W., Shannak, K., Robitaille, Y., Fratkin, J., Koeppen, A.H., Hornykiewicz, O., Kish, S.J. Mov. Disord. (1995) [Pubmed]
  32. Pattern of cytokine receptors expressed by human dendritic cells migrated from dermal explants. Larregina, A.T., Morelli, A.E., Kolkowski, E., Sanjuan, N., Barboza, M.E., Fainboim, L. Immunology (1997) [Pubmed]
  33. CD4+ T cell responses elicited by different subsets of human skin migratory dendritic cells. Morelli, A.E., Rubin, J.P., Erdos, G., Tkacheva, O.A., Mathers, A.R., Zahorchak, A.F., Thomson, A.W., Falo, L.D., Larregina, A.T. J. Immunol. (2005) [Pubmed]
  34. The assays of activities and function of TH, AADC, and GCH1 and their potential use in ex vivo gene therapy of PD. Duan, C.L., Su, Y., Zhao, C.L., Lu, L.L., Xu, Q.Y., Yang, H. Brain Res. Brain Res. Protoc. (2005) [Pubmed]
  35. Parallel up-regulation of catecholamine biosynthetic enzymes by dexamethasone in PC12 cells. Kim, K.T., Park, D.H., Joh, T.H. J. Neurochem. (1993) [Pubmed]
  36. Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes. Eagling, V.A., Tjia, J.F., Back, D.J. British journal of clinical pharmacology. (1998) [Pubmed]
  37. Triple transduction with adeno-associated virus vectors expressing tyrosine hydroxylase, aromatic-L-amino-acid decarboxylase, and GTP cyclohydrolase I for gene therapy of Parkinson's disease. Shen, Y., Muramatsu, S.I., Ikeguchi, K., Fujimoto, K.I., Fan, D.S., Ogawa, M., Mizukami, H., Urabe, M., Kume, A., Nagatsu, I., Urano, F., Suzuki, T., Ichinose, H., Nagatsu, T., Monahan, J., Nakano, I., Ozawa, K. Hum. Gene Ther. (2000) [Pubmed]
  38. Number of striatal D-neurons is reduced in autopsy brains of schizophrenics. Ikemoto, K., Nishimura, A., Oda, T., Nagatsu, I., Nishi, K. Legal medicine (Tokyo, Japan) (2003) [Pubmed]
  39. Cloning and expression of human placental L-Dopa decarboxylase. Siaterli, M.Z., Vassilacopoulou, D., Fragoulis, E.G. Neurochem. Res. (2003) [Pubmed]
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