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Multi-copper oxidases and human iron metabolism.

ABSTRACT: Multi-copper oxidases (MCOs) are a small group of enzymes that oxidize their substrate with the concomitant reduction of dioxygen to two water molecules. Generally, multi-copper oxidases are promiscuous with regards to their reducing substrates and are capable of performing various functions in different species. To date, three multi-copper oxidases have been detected in humans--ceruloplasmin, hephaestin and zyklopen. Each of these enzymes has a high specificity towards iron with the resulting ferroxidase activity being associated with ferroportin, the only known iron exporter protein in humans. Ferroportin exports iron as Fe(2+), but transferrin, the major iron transporter protein of blood, can bind only Fe(3+) effectively. Iron oxidation in enterocytes is mediated mainly by hephaestin thus allowing dietary iron to enter the bloodstream. Zyklopen is involved in iron efflux from placental trophoblasts during iron transfer from mother to fetus. Release of iron from the liver relies on ferroportin and the ferroxidase activity of ceruloplasmin which is found in blood in a soluble form. Ceruloplasmin, hephaestin and zyklopen show distinctive expression patterns and have unique mechanisms for regulating their expression. These features of human multi-copper ferroxidases can serve as a basis for the precise control of iron efflux in different tissues. In this manuscript, we review the biochemical and biological properties of the three human MCOs and discuss their potential roles in human iron homeostasis.

SUBMITTER: Vashchenko G

PROVIDER: S-EPMC3738974 | biostudies-literature | 2013 Jun

REPOSITORIES: biostudies-literature

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Multi-copper oxidases and human iron metabolism.

Vashchenko Ganna G MacGillivray Ross T A RT

Nutrients 20130627 7

Multi-copper oxidases (MCOs) are a small group of enzymes that oxidize their substrate with the concomitant reduction of dioxygen to two water molecules. Generally, multi-copper oxidases are promiscuous with regards to their reducing substrates and are capable of performing various functions in different species. To date, three multi-copper oxidases have been detected in humans--ceruloplasmin, hephaestin and zyklopen. Each of these enzymes has a high specificity towards iron with the resulting f ...[more]

PMID: 23807651

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Project description:Wilson's disease (WD) is a rare hereditary disorder of copper metabolism. Some data suggest that iron metabolism is disturbed in WD and this may affect the course of the disease. The current study aimed to determine whether anti-copper treatment could affect iron metabolism in WD. One hundred thirty-eight WD patients and 102 controls were examined. Serum ceruloplasmin and copper were measured by colorimetric enzyme assay or atomic adsorption spectroscopy, respectively. Routine and non-routine parameters of iron metabolism were measured by standard laboratory methods or enzyme immunoassay, respectively. WD patients, both newly diagnosed and treated, had less serum copper and ceruloplasmin than controls (90.0, 63.0, 22.0 mg/dL, respectively, p < 0.001); in the treated patients blood copper and ceruloplasmin were lower than in untreated patients (p < 0.001). Untreated patients (n = 39) had a higher median blood iron (126.0 vs 103.5 ug/dL, p < 0.05), ferritin (158.9 vs 47.5 ng/mL, p < 0.001), hepcidin (32, 6 vs 12.1 ng/mL, p < 0.001) and sTfR (0.8 vs. 0.7 ug/mL, p < 0.001) and lower blood transferrin (2.4 vs. 2.7 g/L, p < 0.001), TIBC (303.0 vs 338.0 ug/dL, p < 0.001), hemoglobin (13.1 vs 13.9 g/dL, p < 0.01) and RBC (4.3 vs. 4.6, p < 0.002) than controls. Treated patients (n = 99) had a significantly lower median iron (88.0 vs. 126.0 ug/dL, p < 0.001), ferritin (77.0 vs. 158.9 ng/mL, p < 0.005) and hepcidin (16.7 vs. 32.6 ng/mL, p < 001) and higher transferrin (2.8 vs. 2.4 g/L, p < 0.005), TIBC (336.0 vs 303.0 ug/dL, p < 0.001), RBC (4.8 vs. 4.3 M/L, p < 0.001) and hemoglobin (14.4 vs. 13.1 g/dL, p < 0.001) than untreated; the median iron (p < 0.005) was lower, and ferritin (p < 0.005), RBC (p < 0.005) and hepcidin (p < 0.002) were higher in them than in the control group. Changes in copper metabolism are accompanied by changes in iron metabolism in WD. Anti-copper treatment improves but does not normalize iron metabolism.

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Multi-copper oxidases and human iron metabolism.

Publications

Multi-copper oxidases and human iron metabolism.

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