Adrenaline catabolism

In contrast, much is known about the catabolism of catecholamines. Adrenaline (epinephrine) released into the plasma to act as a classical hormone and noradrenaline (norepinephrine) from the parasympathetic nerves are substrates for two important enzymes monoamine oxidase (MAO) found in the mitochondria of sympathetic neurones and the more widely distributed catechol-O-methyl transferase (COMT). Noradrenaline (norepinephrine) undergoes re-uptake from the synaptic cleft by high-affrnity transporters and once within the neurone may be stored within vesicles for reuse or subjected to oxidative decarboxylation by MAO. Dopamine and serotonin are also substrates for MAO and are therefore catabolized in a similar fashion to adrenaline (epinephrine) and noradrenaline (norepinephrine), the final products being homo-vanillic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) respectively. 

One of the best characterized physiological functions of (6R)-tetrahydrobio-pterin (BH4, 43) is the action as a cofactor for aromatic amino acid hydroxylases (Scheme 28). There are three types of aromatic amino acid hydroxylases phenylalanine hydroxylase [PAH phenylalanine monooxygenase (EC 1.14.16.1)], tyrosine hydroxylase [TH tyrosine monooxygenase (EC 1.14.16.2)] and tryptophan hydroxylase [TPH tryptophan monooxygenase (EC 1.14.16.4)]. PAH converts L-phenylalanine (125) to L-tyrosine (126), a reaction important for the catabolism of excess phenylalanine taken from the diet. TH and TPH catalyze the first step in the biosyntheses of catecholamines and serotonin, respectively. Catecholamines, i.e., dopamine, noradrenaline and adrenaline, and serotonin, are important neurotransmitters and hormones. TH hydroxylates L-tyrosine (126) to form l-DOPA (3,4-dihydroxyphenylalanine, 127), and TPH catalyzes the hydroxylation of L-tryptophan (128) to 5-hydroxytryptophan (129). The hydroxylated products, 127 and 129, are decarboxylated by the action of aromatic amino acid decarboxylase to dopamine (130) and serotonin (131), respectively. 

There are two principal catabolic routes for de-sfrucfion of these catecholamines as is illustrated for adrenaline in Fig. 25-5. Monoamine oxidase (MAO)... 

S5mthesized via tyramine (Fig. 30-26), apparently functions in place of noradrenaline. Note fhe precursor-product relationship between dopamine, noradrenaline, and adrenaline. The synthetic pathways to these neurotransmitters involve decarboxylation and hydroxylahon, types of reacfion imporfanf in formation of other transmitters as well. The most important process for ferminafing fhe acfion of released catecholamine transmitters is reuptake by the neurons. High-affinity uptake systems transport the catecholamine molecules back into the neurons and then into the synaptic vesicles. The uptake is specifically blocked by the drug reserpine (Fig. 25-12).7 The dopamine transporter is a major binding site for cocaine (see Fig. 30-28).7 7-7Si Catecholamine trans-miffers are catabolized by two enzymes. One is the... 

The major enzymes in catecholamine catabolism are catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO). COMT transfers a methyl group from S-adenosyhnethionine (SAM) (Chapter 47) to the oxygen at position 3 of the aromatic ring (Fig. 48.1). The pathway taken is a lottery depending on whether the noradrenaline and adrenaline are first of aU methylated (by COMT) or alternatively oxidatively deaminated (by MAO). If chance determines methylation has priority, then the methylated amines normetadrenaline and metadrenaline are formed prior to the MAO reaction and subsequent oxidation to HMMA (hydroxymethoxyman-... 

L-Phenylalanine, Phe L-a-amino-P-phenylpropio-nic acid, an aromatic proteogenic amino acid, Af, 165.2. Phe is essential in the animal diet, and it is both glucogenic and ketogenic The first stage in the catabolism of Phe is hydroxylation to L-tyrosine, which is the precursor of Melanin (see), the neurotransmitter Dopamine (see), the hormones Adrenalin, Noradrenalin and Thyroxin (see separate entries), and other compounds. Tliis first step is catalysed by Phe hydroxylase (a monooxygenase), EC 1.14.16.1. Excess L-tyrosine is broken down to fumarate and acetoacetate (Fig. 1). 

The catabolism of adrenaline takes place in a way analogous to that of noradrenaline. After 0-methylation to metanephrine, or by... 

There are two principle mechanisms for the catabolism of adrenaline and noradrenaline ... 

The major pathway for the catabolism of tyrosine is through C-2 and C-5 hydroxylation of the phenyl ring, giving rise to the intermediate homogentisic acid, and the cleavage of the phenyl ring of this compound, eventually to form fumaric and acetoacetic acid. The route through hydroxylation at C-3 and C-4 to yield 3,4-dihydroxyphenylalanine, the adrenalin compounds, and melanin is quantitatively less important. This pathway is discussed in Chapter 15. 

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