Catecholamines, catechol ring

Epinephrine. Epinephrine (Adrenalin) finds use in a number of situations because of its potent stimulatory effects on both a- and /3-adrcncrgic receptors. Like the other catecholamines, epinephrine is light sensitive and easily oxidized on exposure to air because of the catechol ring system. The development of a pink to brown color indicates oxidative breakdown. To minimize oxidation, solutions of the drug are. stabilized by the addition of reducing agents such as sodium bisulfite. As the free amine, it is used in aqueous solution for inhalation. Like other amines, it forms salts with acids, for example, those now used include the hydrochloride and the bitartratc. Epinephrine is destroyed readily in alkaline solutions and by metals (c.g.. Cu, Fe, Zn), weak... 

Recent studies have focused on the molecular interactions of the endogenous catecholamines, epinephrine and norepinephrine, with the and a,i,-AR subtypes (Cavalli et al., 1996 Hwa and Perez, 1996). Epinephrine and norepinephrine contain a protonated nitrogen atom separated from the aromatic catechol ring by a p-hydroxylethyl chain. The molecular requirement for catecholamine binding to the AR should include the electrostatic interaction between the receptor and the amino group of the ligand. 

Tyrosine also has an important role in the central nervous system and melanocyte and is the precursor of both melanins and catecholamines (epinephrine and norepinephrine). The conversion to these products takes place in the appropriate tissues, usually melanocyte, the central nervous system, or the adrenal gland. In each of these tissues, the enzyme tyrosinase catalyzes the conversion of tyrosine to dihydroxyphenylalanine (DOPA) by hydroxylating the ring adjacent to the parahydroxy group. This is a catechol ring. If this were an amine instead of an amino acid, it would be a catecholamine. The DOPA is a precursor of catecholamines in the adrenal gland and central nervous system. In melanocyte, the DOPA is converted to melanine. In the disease albinism, the tyrosinase in the... 

A combination of decarboxylation and hydroxyla-tion of the ring of tyrosine produces derivatives of o-dihydroxybenzene (catechol), which play important roles as neurotransmitters and are also precursors to melanin, the black pigment of skin and hair. Catecholamines may be formed by decarboxylation of tyrosine into tyramine (step e, Fig. 25-5) and subsequent oxidation. However, the quantitatively more important route is hydroxylation by the reduced pterin-dependent tyrosine hydroxylase (Chapter 18) to 3,4-dihydroxyphenylalanine, better known as dopa. The latter is decarboxylated to dopamine.1313 Hydroxylation of dopamine by an ascorbic acid and... 

Epinephrine (see Figure 1) is synthesized in several steps from either phenylalanine or tyrosine (both amino acids). Two adjacent hydroxyl groups are placed on the aromatic ring, leading to the ring structure called catechol. These hydroxylations form the intermediate L-dopa, which in turn is converted to dopamine (a neurotransmitter), norepinephrine (also a neurotransmitter), and finally epinephrine. Epinephrine together with norepinephrine and dopamine make up the family of biogenic amines called catecholamines. 

An oxidatively induced ring closure occurs during the oxidation of various catecholamines (33)72 at a carbon paste electrode. Whereas the oxidation in 1 M H2SO4 yielded the 1,2-benzoquinone (34), sufficient free amine of 34 was present at pH 3 to allow an internal Michael addition of the adrenaline quinone. As would be expected, the resulting catechol (35) is more easily oxidizable than adrenaline and is converted into the quinone adrenochrome (36) by chemical oxidation by adrenaline quinone. 

Di- and polytopic host-guest systems have provided a convenient starting point for the construction of larger assemblies and many systems of this type are now known. For example, in an early study Kimura et synthesised the catecholamine complex 17. The crown ether unit of this ditopic host was known to be an effective receptor for primary alkyl ammonium salts, whereas the partially protonated form of the hexamine ring had been documented to bind anionic substrates (such as car-boxy lates) or electron-donor substrates (such as catechols). Accordingly, this host forms stable 1 1 complexes with zwitterionic guests such as amino acids, pep-... 

NE is synthesized by tyrosine hydroxylation (meta ring position) followed by decarboxylation and side chain p carbon hydroxylation. The synthesis of this catecholamine is regulated by tyrosine hydroxylase. Tyrosine hydroxylation is also a key step in the synthesis of two other important catecholamines, dopamine and epinephrine. NE is packaged via active transport into synaptic (or chromaffin) vesicles prior to release by neuronal depolarization. The effects of NE are mediated by adrenergic receptors (a or P) which are G protein coupled resulting in either increases or decreases in smooth muscle tone as well as increases in cardiac rate and contractility. These effects arise out of receptor mediated increases in intracellular Ca and activation or inhibition of various protein kinases. The effects of NE are terminated essentially as a result of its active transport into the presynaptic nerve ending via an energy and Na" dependent process which utilizes the norepinephrine transporter (NET). Ultimately, NE and other catecholamines are metabolized by monoamine oxidase (MAO) and catechol-O-methyltransferase (COMT). 

Description Catecholamine is the name of a group of compounds that contain a catechol nucleus (a benzene ring with two adjacent hydroxyl substituents) and an amine group. This group includes the mammalian neurotransmitters or hormones, such as dopamine, norepinephrine, and epinephrine, and nonmammalian compounds such as octopa-mine. Each compound has its own synonyms. Representative Chemical Dopamine Chemical Abstracts Service Registry Number CAS 51-61-6... 

Fig 26.13. Structure of epinephrine and norepinephrine. Epinephrine and norepinephrine are synthesized from tyrosine and act as both hormones and neurotransmitters. They are catecholamines, the term catechol referring to a ring structure containing two hydroxyl groups. 

The first and rate-limiting step in the synthesis of these neuroffansmitters from tyrosine is the hydroxylation of the tyrosine ring by tyrosine hydroxylase, a teffahy-drobiopterin (BH4)-requiring enzyme. The product formed is dihydroxyphenylala-nine or DOPA. The phenyl ring with two adjacent OH groups is a catechol, and hence dopamine, norepinephrine, and epinephrine are called catecholamines. 

From tyrosine, a series of enzymatic reactions including ring hydroxyla-tion, deciurboxylation, deamination, and D-methylation are responsible for over 20 majof metabolites of neurochemical interest. All of the above metabolites retain at least an electroactive phent nudeus, and most provide enhanced detectability via vanillyl or catechol functional groups. Table III provides cyclic voltammctric data in 90% 0.1 M citrate (pH 4)/10% methanol for a series of these metabolites. Substituent effects are evident. Gener-aUy the catecholamines with their OKlihydroxyphenyl structures are easiest to oxidize, followed by vanillyl dmvatives such as normetanephrine and vanillylmandelic acid. Simple phenols such as tyrosine remain the most difficult to oxidize in this series. 

---