Catecholamines auto-oxidation

During ischaemia, the activity of cellular antioxidant systems may be reduced (Ferrari et al. 1985 GaUnanes etal. 1992). In addition, a number of cellular pathways that produce free radicals are primed during ischaemia such as the xanthine/xanthine oxidase system (McCord, 1987), catecholamine auto-oxidation (Jackson et al., 1986) and the arachadonic acid pathway (Halliwell and Gutteridge, 1989). Thus, during early reperfusion there is a burst of free radical production (see Fig. 4.1) that may overwhelm the antioxidant systems of the cells. 

Phenylephrine (27) is a low-potency sympathomimetic amine used as a decongestant. Solutions become coloured due to an auto-oxidation accelerated by light. In a series of experiments, aqueous solutions of the hydrochloride were left under a UV lamp until a tan colour developed. HPLC analysis showed four main products of which one was identified as adrenaline (19). Even after prolonged irradiation, there was never more than 2% adrenaline in the solution. It was assumed that the catecholamine was removed as it formed by further reaction to adrenochrome and melanine, which accounted for the colour [34],... 

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. 

The dioximato-manganese(II) catalyst (3) increases the auto-oxidation rate of epinephrine (a catecholamine derivative) in Na2C03-NaHC03 buffer at room temperature. The proposed mechanism presumes the binding of O2 to the Mn complex, followed by the formation of a ternary intermediate active catalyst-02-substrate complex which disproportionates in the rate-determining step to the product adrenochrome. ... 

As a part of their research prograirune on the chemistry of melanins. Swan and his group in Newcastle have recently studied the tyrosine catalysed and auto-oxidation of dopamine (19) and DOPA (3) and a number of related compounds [57-60]. This group has also investigated the oxidation of 2,4,5-trihydroxyphenylethylamine (20) and synthesised a number of dimeric catecholamines 5,5, 6,6 -tetrahydroxy biphenyl-3,3 -ylenedi(ethyla-mine) (21) 5,5, 6,6 -tetrahydroxybiphenyl-2,2 -ylenedi(ethylamine) (22) 5,5, 6,6 -tetrahydroxybiphenyl-2,3 -ylenedi(ethylamine) (23) 2,3-bis(3,4-dihydroxyphenyl)butane-l,4-diamine (24) and 5,5, 6,6 -tetrahydroxybi-phenyl-3,3 -ylenedialanine (25) [58] and studied their tyrosinase catalysed oxidation, autoxidation, and oxidation with silver oxide, to melanins [59]. 

Graham et al. (1978) conclude that 6-hydroxy-dopamine and 2,4,5-trihydroxyphenylalanine kill cells through the production of H2O2, 02 and HO, while for dopamine and dopa the reaction of qui-none oxidation products with nucleophiles probably also contributes to their cytotoxicity. 0-methyl-ated catecholamines are less susceptible to auto-xidation than their nonmethylated precursors (Miller etal. 1996). Melatonin, which has been shown to be a powerful, endogenous hydroxyl radical scavenger (Tan et al. 1993), is capable of scavenging free radicals produced during catecholamine autoxidation (Miller et al. 1996). 

On the other hand, another study of complex formation between adrenaline (or noradrenaline) and Cu " showed that with catecholamine Cu ratios 2, 2 1 complexes involving the o-diphenol system were formed, which were fairly stable with respect to oxidation. With a catecholamine Cu ratio of approximately 1 1 however, it was believed that a 1 1 complex was formed initially, but this rearranged to a 4 4 complex including both the phenolic group and the side chain. This may then auto-oxidise and interaction between the Cu and the side chain may be responsible for the... 

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