Dihydroxy phenylalanine decarboxylase

L-Dopa. Dopamine itself cannot penetrate the blood-brain barrier however, its natural precursor, L-dihydroxy-phenylalanine (levodopa), is effective in replenishing striatal dopamine levels, because it is transported across the blood-brain barrier via an amino acid carrier and is subsequently decarboxy-lated by DOPA-decarboxylase, present in striatal tissue. Decarboxylation also takes place in peripheral organs where dopamine is not needed, likely causing undesirable effects (tachycardia, arrhythmias resulting from activation of Pi-adrenoceptors [p. 114], hypotension, and vomiting). Extracerebral production of dopamine can be prevented by inhibitors of DOPA-decarboxylase (car-bidopa, benserazide) that do not penetrate the blood-brain barrier, leaving intracerebral decarboxylation unaffected. Excessive elevation of brain dopamine levels may lead to undesirable reactions, such as involuntary movements (dyskinesias) and mental disturbances. 

The enzyme AADC is involved in different metabolic pathways synthesizing two important neurotransmitters dopamine and serotonin [24]. AADC decarboxylates L-dihydroxy-phenylalanine to form dopamine and 5-hydroxytryptophan to produce serotonin. Tryptophan decarboxylase activity is detected in many brain neurons and non-nervous tissue cells. 

Hydroxy tyramine (VIII) is a catechol derivative and a product of both animal and plant origin. It can be isolated from the mammalian heart (41) and human urine (42). It occurs as an intermediate of the coloring matter in the broom Cytisus scuparius Link (43). Conceivably hydroxy-tyramine is derived from 3,4-dihydroxy phenylalanine by decarboxylation. The specific enzyme, dihydroxyphen3dalanine decarboxylase, for catalysis is present in mammalian kidneys (44, 45) and in the rat liver (46). 

Methyldopa (L-a-methyl-3-4-dihydroxy-phenylalanine) is an effective inhibitor of 1-aromatic amino acid (dopa) decarboxylase (Sourkes 1954), There is no evidence that methyldopa is an immunogen methyldopa-specific antibodies have not been reported and there is no evidence of antibody production specific for first-phase metabolites. 

Tyrosine is either used for the biosynthesis of proteins, thyroxine, epinephrine, or melanin, or catabo-lized to yield fumaryl acetoacetate. The biosynthesis of proteins and thyroxine is discussed elsewhere this discussion is restricted to epinephrine and melanin synthesis and tyrosine catabolism. Dopa 3,4-dihydroxy-phenylalanine is an intermediate common to epinephrine and melanin. To yield epinephrine, dopa is first decarboxylated by an enzyme called dopa decarboxylase. This enzyme is present in several mammalian tissues, including the adrenal medulla, where the reaction yields hydroxytryptamine chloride. From this... 

The neurotransmitter must be present in presynaptic nerve terminals and the precursors and enzymes necessary for its synthesis must be present in the neuron. For example, ACh is stored in vesicles specifically in cholinergic nerve terminals. It is synthesized from choline and acetyl-coenzyme A (acetyl-CoA) by the enzyme, choline acetyltransferase. Choline is taken up by a high affinity transporter specific to cholinergic nerve terminals. Choline uptake appears to be the rate-limiting step in ACh synthesis, and is regulated to keep pace with demands for the neurotransmitter. Dopamine [51 -61-6] (2) is synthesized from tyrosine by tyrosine hydroxylase, which converts tyrosine to L-dopa (3,4-dihydroxy-L-phenylalanine) (3), and dopa decarboxylase, which converts L-dopa to dopamine. 

Whilst the term biogenic amine strictly encompasses all amines of biological origin, for the purpose of this article it will be employed to refer to the catecholamine (dopamine, noradrenaline) and serotonin group of neurotransmitters. These neurotransmitters are generated from the amino acid precursors tyrosine and tryptophan, respectively, via the action of the tetrahydrobiopterin (BH4)-dependent tyrosine and tryptophan hydroxylases. Hydroxylation of the amino acid substrates leads to formation of 3,4-dihydroxy-l-phenylalanine ( -dopa) and 5-hydroxytryptophan, which are then decarboxylated via the pyridoxalphosphate-dependent aromatic amino acid decarboxylase (AADC) to yield dopamine and serotonin [4]. In noradrenergic neurones, dopamine is further metabolised to noradrenaline through the action of dopamine-jS-hydroxylase [1]. 

Methyldopa (a-methyl-3,4-dihydroxy-L-phenylalanine), an analog of 3,4-dihydroxyphenylalanine (DOPA), is metabolized by the L-aromatic amino acid decarboxylase in adrenergic neurons to a-methyldopamine, which then is converted to a-methylnorepinephrine. a-Methylnorepi-nephrine is stored in the secretory vesicles of adrenergic neurons, substituting for norepinephrine (NE) itself. Thus, when the adrenergic neuron discharges its neurotransmitter, a-methylnorepinephrine is released instead of norepinephrine. 

DOPA decarboxylase 3,4-dihydroxy-L-phenylalanine carboxy-lyase (EC4.1.1.26)... 

Oates, J. A., Gillespie, L., Udenfriend, S. and Sjoerdsma, A., Decarboxylase inhibition and blood pressure reduction by a-methyl-3,4-dihydroxy-DL-phenylalanine, Science 131, 1890 (1960). 

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