3,4-Dihydroxy-L-phenylalanine

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. 

Tyrosine hydroxylase is the rate-limiting enzyme for the biosynthesis of catecholamines. Tyrosine hydroxylase (TH) is found in all cells that synthesize catecholamines and is a mixed-function oxidase that uses molecular oxygen and tyrosine as its substrates and biopterin as its cofactor [1], TH is a homotetramer, each subunit of which has a molecular weight of approximately 60,000. It catalyzes the addition of a hydroxyl group to the meta position of tyrosine, thus forming 3,4-dihydroxy-L-phenylalanine (l-DOPA). 

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]. 

Fig. 6.2.3a-c AADC assay using HPLC and EC detection of dopamine, a Standard mixture b serum control sample c serum AADC deficiency. DA Dopamine, L-Dopa 3,4-dihydroxy-l-phenylalanine... 

DIHYDROXY-l-PHENYLALANINE see DNA200 1-3,4-DIHYDROXYPHENYLALANIXE see DNA200 (-)-3-(3,4-DIHYDROXYPHENYL)-l-ALANINEsee DXA200... 

An enantioselective oxidation of 3,4-dihydroxy-L-phenylalanine catalyzed by an W-lauxoyl-L- or -D-histidine-Cu(II) complex in the presence of cetyltrimethyl-ammonium bromide as cosurfactant was described by Yamada et al. [54]. 

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)... 

Hydroxy-L-tryptophan 3,4-Dihydroxy-L-phenylalanine (L-dopa) Selenium-Containing Amino Acids Nonprotein Amino Acids in Seeds of the Cucurbitaceae Compounds Involved in Iron Metabolism in Plants Ethylene and Its Precursors... 

The chemo-enzymatic syntheses (O Fig. 41.33) of the aromatic amino acids, 3,4-dihydroxy-L-phenylalanine (DOPA), L-tyrosine, L-tryptophan, 5-hydroxy-L-tryptophan (5-HTP), and analogues thereof, "C-labeled either in the carboxylic- or P-position (Bjurling and Langstrom 1989 Bjurling et al. 1990a, b Sasaki et al. 1999 Harada et al. 1999 Ikemoto et al. 1999) are other important achievements. 

The importance of the labeling position is shown in O Fig. 41.34 where DOPA (3,4-dihydroxy-L-phenylalanine) labeled either in the carboxylic position or the P-position is used to visualize endocrine tumors (Bergstrdm et al. 1996). 

AAc Acrylic acid CMC Carboxymethyl cellulose DHA Dihydroxyacetone DMA Dopamine methacrylamide DORA 3,4-dihydroxy-L-phenylalanine... 

Mussel-derived adhesive protein is known to be the most powerful natural adhesive, and has both flexibility and elasticity [84, 85]. In 1981, Waite and Tanzer discovered 3,4-dihydroxy-L-phenylalanine (DORA) as a key component for the wet-resistant adhesion of mussel adhesive proteins [86]. Non-toxic and non-immu-nogenic effects of mussel proteins have been reported [87-89]. More interestingly, it maintains its adhesion in wet environment, and adheres to virtually any types of synthetic and natnral snrfaces [90]. However, expensive extraction, which requires 10,000 mussels to obtain 1 g of one type of adhesive proteins, and unsuccessful large-scale production limit its practical applications [84]. 

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