Which is the 1st aromatic acid disorder discovered?
Answers
Aromatic amino acid decarboxylase (AAAD), also called DOPA decarboxylase, catalyzes the conversion of L-DOPA to dopamine
AAAD is a preferred name because the enzyme also catalyzes the decarboxylation of 5-hydroxytryptophan to 5-hydroxytryptamine, or serotonin. AAAD is a pyridoxine-dependent dimer of 53 kDa that is widely distributed in the body. AAAD has been identified in monoaminergic neurons and neurons that do not contain other monoamine synthetic enzymes, as well as in glia, kidney and blood vessels. The Km for L-DOPA is 165 µM and the Vmax is 1.5 nmol/min/mg protein (Siow & Dakshinamurti, 1990). Despite its high activity and seemingly constitutive nature, the enzyme is subject to regulation and has important clinical and physiological roles. AAAD is regulated at pre- and posttranslational levels by a number of receptors, pharmacological agents and protein kinases (Berry et al., 1996). The enzyme is solely responsible for the synthesis of ‘trace amines’ such as 2-phenylethylamine, tryptamine and tyramine. Trace amines may act as endogenous modulators of central transmission. They activate G-protein–coupled trace amine receptors (Bunzow et al., 2001), and many are substrates for monoamine transporters. AAAD is of clinical importance in Parkinson’s disease, in which it becomes the rate-limiting step for the conversion of therapeutically administered L-DOPA to dopamine. The pathology of Parkinson’s disease includes a degeneration of dopaminergic cells in the substantia nigra, resulting in a progressive loss of dopamine in the basal ganglia (see Chap. 49). In Parkinson’s disease AAAD activity in cells other than dopaminergic neurons becomes therapeutically important. Inhibition of peripheral AAAD is critical to increase the CNS bioavailability of L-DOPA. L-DOPA is commonly combined with CNS-impermeable inhibitors of AAAD, such as carbidopa or benserazide. AAAD can be inhibited experimentally by methyldopa, hydralazine and aminooxyacetic acid.