Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.10.3.3 (ascorbate oxidase)
 778 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A comprehensive survey of the interaction of the copper proteins and oxygen is presented including a correlation of structure, function, and other properties of the known copper oxidases and of hemocyanin. The origin of their blue color and the structure of copper complexes and copper proteins are related to the oxidation state of copper ion and relevant electronic transitions probably arising from the formation of charge transfer complexes. The oxygen reactions of hemocyanin, ceruloplasmin, and cytochrome oxidase show half-saturation values far below the other Cu enzymes. The formation of hydrogen peroxide as a reaction product is associated with the presence of one Cu atom per oxidase molecule or catalytic system. Water is the corresponding product of the other Cu oxidases with four or more Cu atoms per molecule, except for monoamine oxidase. Mechanisms for the oxidase action of the two and four electron transfer Cu oxidases and tyrosinase are proposed. These reactions account for the number, the oxidation-reduction potential, and the oxidation state of Cu in the resting enzyme, the cyclical change from Cu(II) to Cu(I), the diatomic nature of O(2), the sequence of the oxidation and reduction reactions, and other salient features. The catalytic reactions involved in the oxidation of ascorbic acid by plant ascorbate oxidase, ceruloplasmin, and Cu(II) are compared. Finally the substrate specificity, inhibitory control, and the detailed mechanism of the oxidase activity of ceruloplasmin are summarized.
J Gen Physiol 1965 Sep
PMID:Copper proteins and oxygen. Correlations between structure and function of the copper oxidases. 428 28

1. A method is described for the preparation of a highly purified ascorbic acid oxidase containing 0.24 per cent copper. 2. Using comparable activity measurements, this oxidase is about one and a half times as active on a dry weight basis as the hitherto most highly purified preparation described by Lovett-Janison and Nelson. The latter contained 0.15 per cent copper. 3. The oxidase activity is proportional to the copper content and the proportionality factor is the same as that reported by Lovett-Janison and Nelson. 4. When dialyzed free of salt, the blue concentrated oxidase solutions precipitate a dark green-blue protein which carries the activity. This may be prevented by keeping the concentrated solutions about 0.1 M in Na(2)HPO(4). 5. When highly diluted for activity measurements the oxidase rapidly loses activity (irreversibly) previous to the measurement, unless the dilution is made with a dilute inert protein (gelatin) solution. Therefore activity values obtained using such gelatin-stabilized dilute solutions of the oxidase run considerably higher than values obtained by the Lovett-Janison and Nelson technique. 6. The effect of pH and substrate concentration on the activity of the purified oxidase in the presence and absence of inert protein was studied.
J Gen Physiol 1944 Jan 20
PMID:THE PREPARATION AND PROPERTIES OF HIGHLY PURIFIED ASCORBIC ACID OXIDASE. 1987 82

1. In the absence of protective agents, highly purified ascorbic acid oxidase is rapidly inactivated during the enzymatic oxidation of ascorbic acid under optimum experimental conditions. This inactivation, called reaction inactivation to distinguish it from the loss in enzyme activity that frequently occurs in diluted solutions of the oxidase prior to the reaction, is indicated by incomplete oxidation of the ascorbic acid as measured by oxygen uptake; i.e., "inactivation totals." 2. A minor portion of the reaction inactivation appears to be due to environmental factors such as rate of shaking of the manometers, pH of the system, substrate concentration, and oxidase concentration. The presence of inert protein (gelatin) in the system ameliorates the environmental inactivation to a considerable extent, and variation of the above factors in the presence of gelatin has much less effect on the inactivation totals than in the absence of gelatin. 3. A major portion of the reaction inactivation of the oxidase appears to be due to some factor inherent in the ascorbic acid-ascorbic acid oxidase-oxygen system, possibly a highly reactive "redox" form of oxygen other than H(2)O(2) or H(2)O. The inactivation cannot be attributed to dehydroascorbic acid, the oxidation product of ascorbic acid. 4. Small amounts of native catalase, native peroxidase, native or denatured methemoglobin, and hemin when added to the system, markedly protect the oxidase against inactivation. Cytochrome c has no such protective action. Likewise proteins such as egg albumin, gelatin, denatured catalase, or denatured peroxidase show no such protective action. 5. None of the protective agents mentioned above affect the initial rate of oxygen uptake or change the total oxygen absorbed for complete oxidation of the ascorbic acid, and hence do not act by removal of hydrogen peroxide, per se. 6. Sodium azide and hydroxylamine hydrochloride which inhibit catalase and peroxidase activity also inhibit the protective action of these iron-porphyrin enzymes.
J Gen Physiol 1944 Jan 20
PMID:ON THE INACTIVATION OF ASCORBIC ACID OXIDASE. 1987 83

Multicopper oxidases (MCOs) are a specific group of enzymes that contain multiple copper centers through which different substrates are oxidized. Main members of MCO family include ferroxidases, ascorbate oxidases, and laccases. MCO type of ferroxidases is key to iron transport across the plasma membrane. In Drosophila, there are four potential multicopper oxidases, MCO1-4. No convincing evidence has been presented so far to indicate any of these, or even any insect multicopper oxidase, to be a ferroxidase. Here we show Drosophila MCO3 (dMCO3) is highly likely a bona fide ferroxidase. In vitro activity assay with insect-cell-expressed dMCO3 demonstrated it has potent ferroxidase activity. Meanwhile, the ascorbate oxidase and laccase activities of dMCO3 are much less significant. dMCO3 expression in vivo, albeit at low levels, appears mostly extracellular, reminiscent of mammalian ceruloplasmin in the serum. A null dMCO3 mutant, generated by CRISPR/Cas9 technology, showed disrupted iron homeostasis, evidenced by increased iron level and reduced metal importer Mvl expression. Notably, dMCO3-null flies phenotypically are largely normal at normal or iron stressed-conditions. We speculate the likely existence of a similar iron efflux apparatus as the mammalian ferroportin/ferroxidase in Drosophila. However, its importance to fly iron homeostasis is greatly minimized, which is instead dominated by another iron efflux avenue mediated by the ZIP13-ferritin axis along the ER/Golgi secretion pathway.
Biochim Biophys Acta Gen Subj 2018 08
PMID:Drosophila multicopper oxidase 3 is a potential ferroxidase involved in iron homeostasis. 2968 24