Aromatic L-amino acid decarboxylase modulation and Parkinson's disease.
Aromatic L-amino acid decarboxylase (AAAD) is the second enzyme in the sequence leading to the synthesis of the catecholamines and serotonin, and it is the rate-limiting enzyme for the synthesis of the trace amines. In the striatum AAAD activity is increased by neuronal firing and diminished or enhanced by activation or blocking dopamine (DA) D1 or D2 receptors, respectively. At least two biochemical mechanisms appear responsible for modulation, short-term involving second messengers and possible phosphorylation, and long-term involving protein synthesis. In Parkinson's disease AAAD is the rate-controlling enzyme for the synthesis of DA when L-DOPA is administered and any change of AAAD activity could have clinical consequences. Indeed, the "on-off phenomenon" where there are fluctuations between off-periods of marked akinesia over several hours with on-periods of improved motility may be related to oscillating or poorly modulated AAAD activity and conversion of L-DOPA to DA. Studies are presented demonstrating how AAAD activity can be enhanced in an animal model of Parkinson's disease and how rapid fluctuations of AAAD can be provoked via second messenger system activation.
Neff
N H
NH
Department of Pharmacology, Ohio State University College of Medicine, Columbus 43210, USA.
Hadjiconstantinou
M
M
D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism*; D003342:Corpus Striatum / Q000201:enzymology; D006801:Humans; D010300:Parkinson Disease / Q000201:enzymology*; D012160:Retina / Q000201:enzymology
D001142:Aromatic-L-Amino-Acid Decarboxylases