Superoxide dismutase copper complexes

Advances include radioprotective drugs applied during radiotherapy of neoplastic diseases. Effects similar to the enzyme superoxide dismutase have been found in copper complexes of Schiffs bases (derived from different amino acids and salicylaldehyde). Activity of complexes is dependent on their structures. The structural changes of their chelate rings are responsible for their effects on free radicals produced in organisms during radiation. Complexes have square pyramidal pentacoordination, which is similar to the coordination polyhedron in the active center of the Cu-dependent superoxide dismutase. The complexes used as radio-protective drugs play an important role in radiotherapy. They protect healthy tissues and cells from injurious radiation. ° ... 

More copper is found in the brain and heart than in any other tissue except for liver, where it is stored as copper thionein and released as ceruloplasmin or in the form of a complex with serum albumin. The high metabolic rate of the heart and brain requires relatively large amounts of copper metalloenzymes including tyrosinase, cytochrome c oxidase, dopamine-/3-hydroxylase, pyridoxal-requiring monamine oxidases, and Cu-Zn superoxide dismutase. Copper deficiency, which can occur for reasons analogous to those discussed above for Fe and Zn, leads to brain disease in infants, anemia (since cytochrome oxidase is required for blood formation), and heart disease. Few details are known about the molecular basis for copper uptake from foods. 

MTip and 1/T2 are the paramagnetic contribution to longitudinal and transverse relaxation rates of F (1/Ti and I/T2), Tjm is the longitudinal relaxation time of F in the first coordination shell of the paramagnetic center, copper(II), Tm the residence time that is the time a F ion is bound to copper(II) before it exchanges and (M ) is the stability constant of the superoxide dismutase-F complex. 

Kensler, T.W. and Trush, M.A, (1983). Inhibition of oxygen radical metabolism in phorbol ester-activated polymorphonuclear leukocytes by an antitumor promoting copper complex with superoxide dismutase-mimetic activity. Biochem. Pharmacol. 32, 3485-3487. 

Copper is part of several essential enzymes including tyrosinase (melanin production), dopamine beta-hydroxylase (catecholamine production), copper-zinc superoxide dismutase (free radical detoxification), and cytochrome oxidase and ceruloplasmin (iron conversion) (Aaseth and Norseth 1986). All terrestrial animals contain copper as a constituent of cytochrome c oxidase, monophenol oxidase, plasma monoamine oxidase, and copper protein complexes (Schroeder et al. 1966). Excess copper causes a variety of toxic effects, including altered permeability of cellular membranes. The primary target for free cupric ions in the cellular membranes are thiol groups that reduce cupric (Cu+2) to cuprous (Cu+1) upon simultaneous oxidation to disulfides in the membrane. Cuprous ions are reoxidized to Cu+2 in the presence of molecular oxygen molecular oxygen is thereby converted to the toxic superoxide radical O2, which induces lipoperoxidation (Aaseth and Norseth 1986). 

Transition metal hydroperoxo species are well established as important intermediates in the oxidation of hydrocarbons (8,70,71). As they relate to the active oxygenating reagent in cytochrome P-450 monooxygenase, (porphyrin)M-OOR complexes have come under recent scmtiny because of their importance in the process of (poiphyrin)M=0 formation via 0-0 cleavage processes (72-74). In copper biochemistry, a hydroperoxo copper species has been hypothesized as an important intermediate in the catalytic reaction of the copper monooxygenase, dopamine P-hydroxylase (75,76). A Cu-OOH moiety has also been proposed to be involved in the disproportionation of superoxide mediated by the copper-zinc superoxide dismutase (77-78). Thus, model Cun-OOR complexes may be of... 

Sulfur ligands, 633-655 coordination ability, 516 Sulfur monoxide metal complexes instability, 636 Superoxide dismutase, 773 copper complexes, 772 Superoxo complexes, 315-330 binuclear, 323, 325 reactions, 330 bridged... 

Gold sodium thiomalate provides a stimulus for liver, kidney and possibly other cells to change the body distribution of zinc and copper. Proteins such as metalloproteins, superoxide dismutase and metallothioneins19 help the cell carry out this task. These essential metals are important in the physiological processes relevant to rheumatoid arthritis, and thus it also appears possible that the gold complexes may mediate their antiarthritic activity through an effect on the metabolism of zinc and copper. 

In in vitro studies penicillamine inhibited angiotensin-con-verting enzyme (ACE) and carboxypeptidase (930). Penicillamine interferes with the functions of the copper-containing enzyme ceruloplasmin, and some of the penicillamine- and copper-containing complexes formed in vivo have a superoxide dismutase effect (931). In patients with scleroderma, penicillamine normalized collagen metabolism, by inhibiting beta-galactosidase activity (932). 

Barik A, Mishra B, Shen L, Mohan H, Kadam RM, Dutta S, Zhang HY, Priyadarsini KI. 2005. Evaluation of a new copper(II)-curcumin complex as superoxide dismutase mimic and its free radical reactions. Free Radio Biol Med 39 811-822. 

The most common metal encountered in electron transfer systems is iron, although copper and manganese play vital functions. Merely to emphasise the complexity of the catalysts that are used in biology, the structures of the active sites of ascorbate oxidase (Fig. 10-11) and superoxide dismutase (Fig. 10-12) are presented. It is clear that we have only just begun to understand the exact ways in which metal ions are used to control the reactivity of small molecules in biological systems. 

Copper, silver and gold - The paramagnetism of Cu11 has limited the use of NMR for the direct study of copper complexes, but information is readily obtained from studies of ligand nuclei. For example, the broadening of the NMR signal by copper in copper-zinc and copper-cobalt superoxide dismutases (SODs) has been used to determine the distance between the copper and the proton on bound formate (Sette et al., 1992). Also, broadening of the formate 13C NMR resonance reveals information about the orientation of the formate. 

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