Dopamine from tyrosine

Decarboxylations of amino acids are involved in the production of serotonin from tryptophan and of dopamine from tyrosine. 

Isoquinoline alkaloids are derived from tyrosine through the intermediacy of 3,4-dihydroxyphenylethylamine (dopamine) and a carbonyl unit of various origins. The genesis of tyramine, and dopamine from tyrosine has been described previously (see Chapter 28). In contrast to benzylisoquinoline alkaloids (see below), the formation of isoquinoline alkaloids usually involves the amine and an a-ketoacid instead of an amine and aldehyde. However, several compounds can... 

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. 

Catecholamines. The catecholamines, epinephrine (EPl adrenaline) (85), norepinephrine (NE noradrenaline) (86) (see Epinephrine and norepinephrine), and dopamine (DA) (2), are produced from tyrosine by the sequential formation of L-dopa, DA, NE, and finally EPl. EPl and NE produce their physiological effects via CC- and -adrenoceptors, a-Adrenoceptors can be further divided into CC - and a2-subtypes which in turn are divided... 

Dopamine. Dopamine (DA) (2) is an intermediate in the synthesis of NE and Epi from tyrosine. DA is localized to the basal ganglia of the brain and is involved in the regulation of motor activity and pituitary hormone release. The actions of DA are terminated by conversion to dihydroxyphenylacetic acid (DOPAC) by monoamine oxidase-A and -B (MAO-A and -B) in the neuron following reuptake, or conversion to homovanillic acid (HVA) through the sequential actions of catechol-0-methyl transferase (COMT) and MAO-A and -B in the synaptic cleft. 

Catecholamines are biogenic amines with a catechol (o-dihydroxy-benzol) structure. They are synthesized in nerve endings from tyrosine and include dopamine, noradrenaline (norepinephrine) and adrenaline (epinephrine). 

Three amines—dopamine, norepinephrine, and epinephrine—are synthesized from tyrosine in the chromaffin cells of the adrenal medulla. The major product of the adrenal medulla is epinephrine. This compound constimtes about 80% of the catecholamines in the medulla, and it is not made in extramedullary tissue. In contrast, most of the norepinephrine present in organs innervated by sympathetic nerves is made in situ (about 80% of the total), and most of the rest is made in other nerve endings and reaches the target sites via the circu-... 

Dopamine (5-hydroxylase is a copper-containing enzyme involved in the synthesis of the catecholamines norepinephrine and epinephrine from tyrosine in the adrenal medulla and central nervous system. During hy-droxylation, the Cu+ is oxidized to Cu " reduction back... 

Dopamine is formed from tyrosine by hyclroxylation with tyrosine hydroxylase and the removal of a CO2 group by aromatic amino acid decarboxylase. The catecholamine is found in high concentrations in parts of the brain—the caudate nucleus, the median eminence, the tuberculum olfactorium, and the nucleus accumbens. Dopamine appears to act as an inhibitory neurotransmitter. 

The answers are 327-a, 328-c 329-d. (Hardman, pp 120, 250, 582-583.) Epinephrine is made from tyrosine in a series of steps through L-dopa, dopamine, NE, and finally epinephrine. The conversion of tyrosine to dopa by tyrosine hydroxylase is the rate-limiting step in this pathway. Epinephrine constitutes about 80% of the catecholamines in the adrenal medulla. The enzyme that synthesizes epinephrine from NE is also found in certain areas of the CNS. 

Known most famously for their part in the fight or flight response to a threat, challenge or anger, adrenaline (epinephrine) and dopamine from the adrenal medulla and noradrenaline (norepinephrine), mainly from neurones in the sympathetic nervous system are known collectively as catecholamines. Synthesis follows a relatively simple pathway starting with tyrosine (Figure 4.7). 

A more recent strategy deveioped for Parkinson s disease is dopamine replacement, which began with L-dihydroxyphenyiaianine (L-DOPA or ievodopa). L-DOPA is converted from tyrosine by the enzyme tyrosine... 

The results with methylphenidate, however, are more impressive. Two of three studies found a significant effect and the third found improvement on the patients subjective evaluation. Although amphetamine and methylphenidate are similar in their pharmacology, they differ in some respects. Amphetamine releases dopamine from newly synthesized pools (a-methyl-p-tyrosine-sensitive pool) whereas methylphenidate releases dopamine from storage sites (reserpine-sensitive sites). This pharmacological difference could be related to the apparent greater efficacy of methylphenidate. 

Morphine and codeine biosynthesis (Samuelsson, 1999 Herbert et al., 2000 Novak et al., 2000) Studies on the biosynthesis of morphine have been carried out mainly on cell cultures mainly of Coptis japonica and species of Thalictrum. Two enzymes (tyrosine decarboxylase and phenolase) catalyze the formation of dopamine from one molecule tyrosine. Dopamine is also the key intermediate in the biosynthesis of mescaline. 

Other important nitrogen-containing compounds made from amino acids include the catecholamines (dopamine, norepinephrine, and epinephrine), which are synthesized from tyrosine creatine, which is synthesized from arginine and glycine histamine, which is synthesized from histidine and serotonin, which is synthesized from tryptophan. 

Dopamine, a catecholamine, is synthesized in the terminals of dopaminergic neurons from tyrosine, which is transported across the blood-brain barrier by an active process (Figure 23.7). The rate-limiting step in the synthesis of dopamine is the conversion of 1-tyrosine to 1-dihydroxy-phenyta-lanine (1-dopa), catalyzed by the enzyme tyrosine hydroxylase, which is present within catechola-minergic neurons. 

Dopamine, which is essential for the control of movement, is made from tyrosine (or phenylalanine, because tyrosine is a direct product of phenylalanine metabolism). 

Dopamine may alternatively be formed from tyrosine via hydroxylation of L-dopa which is decarboxylated. However, inverse isotope dilution experiments to study the formation of dopamine and dopa have shown that this is probably a minor pathway in peyote (176). It has been shown that L-tyrosine is incorporated into alkaloids in peyote three times more efficiently than into protein (344). 4-Hydroxy-3-methoxyphenethylamine can be methylated to 3,4-dimethoxy-phenethylamine (homoveratrylamine), which may be viewed as a dead-end product in Scheme 2 (10, 203). Phenylalanine is probably not a precursor of the... 

The most abundant alkaloid in Coryphantha macromeris, normacromerine, has been shown to originate from tyrosine (330). Tyramine and JV-methyltyramine are efficiently incorporated into normacromerine while octopamine and dopamine are poor precursors. Norepinephrine, epinephrine, normetanephrine, and meta-nephrine have all been shown to be biosynthetically incorporated into normacromerine, and they have also been shown to be naturally occurring trace intermediates in this cactus species (331, 334). Normacromerine is only slowly converted to macromerine in C. macromeris (332). The results indicate that alternative pathways to normacromerine exist precise conclusions regarding the biosynthesis of normacromerine must await further studies. 

Epinephrine [ep ee NEF rin] is one of five catecholamines—epinephrine, norepinephrine, dopamine, dobutamine, and isoproterenol—commonly used in therapy. The first three catecholamines occur naturally, the latter two are synthetic compounds (see Figure 6.7). Epinephrine is synthesized from tyrosine in the adrenal medulla and released, along with small quantities of norepinephrine, into the blood stream. Epinephrine interacts with both a and p receptors. At low doses, p effects (vasodilation) on the vascular system predominate, whereas at high doses, a effects (vasoconstrictor) are strongest. 

While both dopamine and norepinephrine are derived from tyrosine, serotonin (5-hydroxytryptamine, 5-HT) is derived from tryptophan. All three transmitters are very important... 

The catecholamines - dopamine, norepinephrine, and epinephrine are successively derived from tyrosine. S m-thesis occurs in the nerve terminals and in the adrenal gland. Tyrosine hydroxylase catalyzes the first step (Figure 10.2a) and is the major site of regulation (inhibition by dopamine and noradrenaline, activation by cAMP). This step gives rise to 3,4-dihydroxyphenylalanine (L-DOPA), which in turn is a substrate for L-aromatic acid decarboxylase. De-... 

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