Oxidation of catecholamines

The deep red to violet colored compounds obtained on oxidation of catecholamines are known as the aminochromes1 and have attracted... 

A. Oxidations of Catecholamines in Dilute Solution 1. General Comments... 

The oxidation of catecholamines in the presence of tyrosinases and polyphenolases has been widely studied, and the subject has been adequately discussed in the literature. References 12 and 31-41 will serve as a guide to further reading on the subject. 

The chemical transformations that occur on ultraviolet irradiation of adrenaline and noradrenaline solutions have been investigated by Walaas, who showed that the initial photoactivation of the catecholamine molecule is a direct effect (i.e., it is not dependent on the presence of trace metals) and that the activated species, probably free radical in nature, are readily autoxidizable in air.61 Walaas suggests that the activation of catecholamines by ultraviolet radiation may involve electronic changes similar to those initially occurring during the metal-catalyzed oxidation of catecholamines at an intermediate pH.14,61... 

The formation of aminochromes by the oxidation of catecholamines is usually a very rapid process. However, recent work has suggested that some of the highly reactive intermediate species, which are formed during the initial stages of the catecholamine oxidations and which have been largely overlooked in the past, may be of considerable physiological importance. 

More definite evidence for the transient existence of the un-cyclized l-(jS-aminoethyl)-3,4-benzoquinones has been obtained recently by Kodja and Bouchilloux,77 78 who noted that a transient yellow color (Amax ca. 385 mp) was occasionally observed during the enzymic oxidations of catecholamines (particularly in unbuffered systems at low temperatures). This phenomenon was probably due to the formation of the transient o-quinones. (The absorption maximum of o-benzoquinone, the effective chromophore of the open-chain quinones, is known to occur at ca. 390 mp.79) An absorption maximum at 390 mp is characteristic of the formation of the dopa-quinone chromophore during oxidation of small C -terminal tyrosine peptides in the presence of tyrosinase.37 48 Similar spectroscopic features were observed when the oxidations were carried out with lead dioxide in sulfuric acid solutions (pH> 1). If the initial oxidation was carried out for a short period of time, it was possible to regenerate the original catecholamines by reduction (e.g. with sodium bisulfite, potassium iodide, and zinc powder) and to show that the 385 mp peak disappeared.77,78 Kodja and Bouchilloux were also able to identify 2,4-dinitrophenylhydrazones of several of the intermediate non-cyclized quinones by paper chromatography and spectroscopy (Amax n weakly acid solution ca. 350 mp with a shoulder at ca. 410 mp).77,78... 

Another theory of mental illness postulates endogenous alkaloid formation. Aldehydes formed by oxidation of catecholamines as well as formaldehyde and acetaldehyde are present in tissues in small amounts. Condensation with amines could generate Schiff bases and alkaloids as in Fig. 25-10. This "plant chemistry" is spontaneous and can apparently take place in the brain, where it may have a potent effect. 

Monoamine oxidase, tyrosine hydroxylase, and L-amino acid oxidase generate hydrogen peroxide as their reaction product. Hydrogen peroxide is also produced by auto-oxidation of catecholamines in the presence of vitamin C. Moreover, phospholipase A2 (PLA2), cyclooxygenase (COX), and lipoxygenase (LOX), the enzymes associated with arachidonic acid release and the arachidonic acid cascade,... 

Auto-oxidation of catecholamines also leads to formation of the polymeric pigment neuromelanin that increases with age and is responsible for the dark coloration of DA-pro-ducing cells in the substantia nigra and the norepinephrine neurons of the locus coeruleus (42). A physiological role for this polymer is not established, and there is no evidence to support its involvement either in normal loss of DA neurons with aging or in the pathophysiology of PD. 

Scheme 5. Electrochemical oxidation of catecholamines to melanoid pigments (257).

Kruk, L, 1985, The identification by electron spin resonance spectroscopy of singlet oxygen formed in the photo-oxidation of catecholamines, Z Phys. Chem. (Leipzig) 226, 1239-1242. 

The oxidation of catecholamines like epinephrine has been widely used as source for superoxide dismutase assays. Upon oxidation the catecholamines are transformed to the coloured product adrenochrome. The rate of oxidation by superoxide is inhibited in the presence of superoxide dismutases Likewise the autoxidation of catecholamines at alkaline pH-values is diminished Intriguingly, low molecular mass copper complexes which display superoxide dismutase activity accelerate the autoxidation Therefore, the interaction between superoxide and catecholamines and its inhibition by SOD is thought not to be a simple chemical reactionRecently, this reaction was investigated in more detail Whilst adrenalin autoxidation is very specifically inhibited by SOD, the reaction with other catecholamines like noradrenalin or dihydroxyphenylalanine, having no free amino group, is much less specific. Only 20 % inhibition by CujZnjSuperoxide dismutase are observed. The autoxidation reaction itself is very complex (Scheme 2) and still not fully understood. 

The oxidation of catecholamines by the hydroperoxidase activity of lipoxygenase (EC 1.13.11.12) is documented by Rosei et al. (1994) and NOnez-Delicado et al. (1996). o-Diphenols are easily studies spectrophotometrically since, when oxidised, they render coloured compounds, quinones, or their corresponding aminochromes. In the case of isoprenaline the maximum of the oxidation product was developed at 490 nm (NOnez-Delicado et al. 1999), which corresponds to that of the aminochrome product (Jim nez et al. 1985, NOnez-Delicado et al. 1996). 

Sutor, B., and ten Bruggencate, G., 1990, Ascorbic acid A useful reductant to avoid oxidation of catecholamines in electrophysiological experiments in vitro Neurosci. Lett. 116 287-292. 

Now the next question Is, what substances are causing the different peaks Many workers have assumed that peak I Is caused by the oxidation of catecholamines such as noradrenaline. However there Is a problem In that the oxidation potentials for ascorbic acid and the catecholamines are not very different. A further problem we have found Is that oxidation potentials measured In the brain and measured In vitro can be very different. Exposing a carbon paste electrode to rats brain makes It more active. In Table 4 we give results for the... 

The oxidation of catecholamines is catalysed by a number of enzymes which are widely distributed in the plant and animal kingdoms. The quinonoid pathway may exist as a minor but normal metabolic pathway for these substances in mammals. This question will be discussed in more detail later (see p. 318). In general, the enzymes responsible for the oxidation of the catecholamines, such as tyrosinase and ceruloplasmin, contain copper. 

Borg [79] studied (a) the ceric sulphate oxidation of adrenaline, noradrenaline and DOPA in add solution (b) the ferricyanide oxidation of adrenaline and DOPA in alkaline solution and (c) the permanganate oxidation of adrenaline at neutral pH. Free radical intermediates, which were thought to be semiquinones formed in the first step of the oxidation, were detected in the reaction mixtures by means of e.p.r. spectroscopy. They were shown to have arisen before the aminochrome stage as the e.p.r. spectrum of oxidised adrenochrome was different from that observed in the initial stages of the oxidation of adrenaline. Thus the first stage in the oxidation of catecholamines involves the formation of a semiquinone [79]. 

The aminochromes readily undergo substitution reactions with molecular iodine or bromine to form 7-iodo- or 7-bromo-derivatives [26-29] (p. 294). The oxidation of catecholamines with iodine or iodates usually results in the formation of 7-iodoaminochromes with the unhalogenated aminochrome being formed as an intermediate in the reaction (26-29, 179]. 

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