Catecholamine autoxidation

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). 

The effect of non-participating ligands on the copper catalyzed autoxidation of cysteine was studied in the presence of glycylglycine-phosphate and catecholamines, (2-R-)H2C, (epinephrine, R = CH(OH)-CH2-NHCH3 norepinephrine, R = CH(OH)-CH2-NH2 dopamine, R = CH2-CH2-NH2 dopa, R = CH2-CH(COOH)-NH2) by Hanaki and co-workers (68,69). Typically, these reactions followed Michaelis-Menten kinetics and the autoxidation rate displayed a bell-shaped curve as a function of pH. The catecholamines had no kinetic effects under anaerobic conditions, but catalyzed the autoxidation of cysteine in the following order of efficiency epinephrine = norepinephrine > dopamine > dopa. The concentration and pH dependencies of the reaction rate were interpreted by assuming that the redox active species is the [L Cun(RS-)] ternary complex which is formed in a very fast reaction between CunL and cysteine. Thus, the autoxidation occurs at maximum rate when the conditions are optimal for the formation of this species. At relatively low pH, the ternary complex does not form in sufficient concentration. 

There is still not complete agreement as to whether catecholamines undergo a true autoxidation in dilute aqueous solution at neutral... 

Xanthine oxidase/xanthine Electrolytic reduction of Oj Photoreduction of riboflavin Autoxidation of pyrogallol Autoxidation of catecholamines >5°) NADH oxidation by phenazine methosul-fate... 

Autoxidation of catecholamines ->5oi Autoxidation of sulfite Oxidation of hydroxylamine ... 

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 detection limit of the autoxidation assay is 0.5 nM superoxide dismutase The oxidation of adrenalin is followed at 480 nm spectrometrically. 850 pi 100 mM carbonate buffer, pH 10 and 100 pi water or sample are mixed. The reaction is started with 50 pi catecholamine stabilized at pH 2. AA/min is followed. Due to its convenience, this method can be employed in homogenates and other biological samples However, the assay can interfere with reduced glutathione, causing an... 

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]. 

Enzymatic oxidation of 2,4,5-trihydroxyphenylethylamine (20) gave a relatively stable red product, exhibiting absorption maxima at ca. 272 nm and 490 nm [59], which was probably the p-quinonoid indoline derivative (26)[59, 61-63]. Melanins were eventually obtained, in all cases on autoxidation (pH 8) and enzymatic oxidation (pH 6-8) of the dimeric catecholamines (21, 22, 23, 24 and 25). 

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