Aromaticl-amino acid decarboxylase: A neglected and misunderstood enzyme

Abstract

Classically, aromatic L-amino acid decarboxylase (AADC) has been regarded as an unregulated, rather uninteresting enzyme. In this review, we describe advances made during the past 10 years, demonstrating that AADC is regulated both pre- and post-translation. The significance of such regulatory mechanisms is poorly understood at present, but the presence of tissue specific control of expression raises the real possibility of AADC being involved in processes other than neuro-transmitter synthesis. We further discuss clinical and physiological situations in which such regulatory mechanisms may be important, including the intriguing possibility of AADC gene regulation being linked to that of factors thought to have a role in apoptosis and its prevention.

Two novel variants in the DOPA decarboxylase gene: association with bipolar affective disorder

“…Although DDC is not a rate-limiting enzyme, it is now clear that it is indeed regulated (for review see 29 ). This fact raises some even more intriguing perspectives as to its potential pathophysiological role, especially concerning a range of neuropsychiatric disorders.…”

Comparative sequencing and association studies of aromatic L-amino acid decarboxylase in schizophrenia and bipolar disorder

“…1 AADC does not catalyse the rate limiting step in either pathway, but is rate limiting in the synthesis of 2-phenylethylamine (2PE) which is a positive modulator of dopaminergic transmission and a candidate natural psychotogenic compound. 1 We and others have proposed that polymorphism in AADC resulting in altered 2PE activity might contribute to the pathogenesis of psychosis. 1,2 In order to test this hypothesis, we have used denaturing high performance liquid chromatography (DHPLC) 3 to screen 3943 bases of the AADC gene and its promoter regions for variants that might affect protein structure or expression in 15 unrelated people with schizophrenia, and 15 unrelated people with bipolar disorder.…”

Quantitative expression analysis and prognostic significance of L-DOPA decarboxylase in colorectal adenocarcinoma

“…This is especially apparent with lung cancers of small-cell origin, although variants showing no protein expression have been observed as well (Berry et al, 1996). Remarkable increase in DDC activity, in comparison with normal tissue levels, is also seen in primary intestinal cancer and its related metastases in the spleen and liver (Gilbert et al, 1995).…”

“…L-DOPA decarboxylase is a PLP-dependent enzyme participating in the catecholamine biosynthesis pathway, responsible principally for the synthesis of the key neurotransmitters DA and 5-HT (Christenson et al, 1972). Biogenic amines are generally considered to participate in various processes, such as angiogenesis, cell proliferation, differentiation and apoptosis (Berry et al, 1996;Medina et al, 1999;Lang et al, 2005), which implies a potentially significant role of DDC in cancer pathobiology and progression. Interestingly enough, it has recently been shown that catecholamines, including DA itself, inhibit erythrocyte apoptosis by preventing scramblase activation and subsequent phosphatidylserine exposure on the cell membrane (Lang et al, 2005), which in turn triggers clearance of apoptotic cells by macrophages.…”

“…Remarkable increase in DDC activity, in comparison with normal tissue levels, is also seen in primary intestinal cancer and its related metastases in the spleen and liver (Gilbert et al, 1995). The significance of this increase in DDC activity and resultant monoamine synthesis by the cancer cells is still unknown (Berry et al, 1996), yet it is closely related to the implication of DDC in cancer.…”