Dopamine autoxidation

Chiueh, C.C., Miyake, J., Peng, M.T. Role of dopamine autoxidation, hydroxyl radical generation, and calcium overload in underlying mechanisms involved in MPTP-induced parkinsonism. Adv. Neurol. 60 251, 1993. 

Dopamine, a strong water-soluble antioxidant, was identified in banana fruit (Musa cavendishii) by Kanazawa and Sakakibara (2000). Banana fruit contained high levels in the pulp and peel 2.5-10 mg/100 g and 80-560 mg/100 g, respectively. A banana water extract was reported to suppress the autoxidation of linoleic acid by 65-70% after a 5-day incubation in an emulsion system, as determined from peroxide value and thiobarbituric acid reactivity (Kanazawa and Sakakibara 2000). 

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. 

The autoxidation of ascorbate, a cosubstrate of dopamine P-monooxygenase, induces the degradation of most proteins including catalase and dopamine p-monooxygenase, but with the exception of (Cu,Zn)-SOD. Catalase protects dopamine P-monooxy-genase and is therefore generally added in the assay systems . The apparent activation or rather the stabilization of the enzyme (6.5 pg) by small amounts of catalase (3.1 pg) was enhanced by native but not by boiled SOD (100 pg) and also by similar amounts of serumalbumin (100 pg) or of boiled catalase (65 pg)... 

The effect of SOD points to the intervention of Oj in the autoxidation of ascorbate. Proteins in large amounts could react with the strong oxidizing agent formed in this Udenfriend s system , thus protecting the enzyme. The ineffectiveness of boiled SOD could be due to its amino-acid composition (See Sect. 4.1.2). While O did not inactivate dopamine P-monooxygenase the rate pf inactivation in the presence of... 

Graham DG, Tiffany SM, Bell WR, Jr, Gutknecht WF. 1978. Autoxidation versus covalent binding of quinones as the mechanism of toxicity of dopamine, 6-hydro-xydopamine, and related compounds toward Cl300 neuroblastoma cells in vitro. Mol Pharmacol 14 644-653. 

Fomstedt, B. Bmn, A. Rosengren, E. and Carlsson, A. The apparent autoxidation rate of catechols in dopamine-rich regions of human brains increases with the degree of depigmentation of substantia nigra. J Neural Trans 1 279-295, 1989. 

Fomstedt, B. Pilebad, E. and Carlsson, A. In vivo autoxidation of dopamine in guinea-pig striatum increases with age. JNeurochem 55 655-659, 1990. 

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). 

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]. 

The autoxidations of dopamine (19) and DOPA (3) were carried out in phosphate buifer at pH 8-0, and the (much faster) enzymatic oxidations were carried out at pH 6-8, also in a phosphate buffer. In the latter case, the... 

The work of Swan and his collaborators also demonstrated, contrary to the expectations of the Raper-Mason hypothesis, that the melanin pigment derived from dopamine (16) by autoxidation differs substantially from a similarly derived dopa-melanin. In particular more uncyclised chains and intermonomer carbon-nitrogen linkages were shown to be present in the dopamine pigment. 

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