Copper availability contributes to iron perturbations in human nonalcoholic fatty liver disease

BACKGROUND ; AIMS: Iron perturbations are frequently observed in nonalcoholic fatty liver disease (NAFLD). We aimed to investigate a potential association of copper status with disturbances of iron homeostasis in NAFLD. METHODS: We retrospectively studied 140 NAFLD patients and 25 control subjects. Biochemical and hepatic iron and copper parameters were analyzed. Hepatic expression of iron regulatory molecules was investigated in liver biopsy specimens by reverse-transcription polymerase chain reaction and Western blot analysis. RESULTS: NAFLD patients had lower hepatic copper concentrations than control subjects (21.9 +/- 9.8 vs 29.6 +/- 5.1 microg/g; P = .002). NAFLD patients with low serum and liver copper concentrations presented with higher serum ferritin levels (606.7 +/- 265.8 vs 224.2 +/- 176.0 mg/L; P < .001), increased prevalence of siderosis in liver biopsy specimens (36/46 vs 10/47 patients; P < .001), and with elevated hepatic iron concentrations (1184.4 +/- 842.7 vs 319.9 +/- 451.3 microg/g; P = .020). Lower serum concentrations of the copper-dependent ferroxidase ceruloplasmin (21.7 +/- 4.1 vs 30.4 +/- 6.4 mg/dL; P < .001) and decreased liver ferroportin (FP-1; P = .009) messenger RNA expression were found in these patients compared with NAFLD patients with high liver or serum copper concentrations. Accordingly, in rats, a reduced dietary copper intake was paralleled by a decreased hepatic FP-1 protein expression. CONCLUSIONS: A significant proportion of NAFLD patients should be considered copper deficient. Our results indicate that copper status is linked to iron homeostasis in NAFLD, suggesting that low copper bioavailability causes increased hepatic iron stores via decreased FP-1 expression and ceruloplasmin ferroxidase activity thus blocking liver iron export in copper-deficient subjects.

Copper Commando Index – vol. 1

Index for volume 1 (Aug. 1942-Aug. 1945) lists personal names, places, subjects; page and issue numbers.

Constitution and Specific Gravity of the Ternary Mattes Cu2S-FeS-PbS.

The constitution of the ternary mattes CU2S-FeS-PbS has never been completely investigated. Fulton and Goodner 1) have investigated the binary mattes CU2S-FeS, CU2S-PbS, PbSFeS and have shown that the three binaries show eutectics. There has been no attempt however to draw the complete ternary diagram. The following work is intended to be a contribution toward the completion of this diagram by first of all pointing out those mattes which separate on melting into two layers, and second by determining the specific gravities of mattes of different compositions.

The Acropolitan - v. 1, no. 2

In this issue...Ore Dressing, John Quinn, Butte, Montana, copper, Mt. View mine, Anaconda Copper Mining Company

The Acropolitan - v. 2, no. 1

In this issue...Chancellor Brannon, Library, Dancing Club, Engineering Education, copper, Philipsburg Mining Co., Montana, Mines Gymnasium, Coach McAuliffe

The Acropolitan - v. 2, no. 4

In this issue... "M" Club, Mining District Basketball Tournament, Butte High School, Butte Central High School, Butte, Montana, Bob Nesbitt, Northern Pacific Railway, Co-ed Dance

The Acropolitan - v. 2, no. 5

In this issue...School of Mines Smoker, Handball Tournament, Anaconda Copper Mining Company, Thornton Hotel, President Coolidge, Clark Park, Butte, Montana, Professor Simons

The Acropolitan - v. 7, no. 2

In this issue...Dr. Coolbaugh, Montana Society of Engineers, Leonard Hoist House, Dancing Club, copper, Boulder Batholith, gold, Butte, Montana

The Acropolitan - v. 8, no. 2

in this issue...Annie Anderson, Hecla MIne, F. A. Thomson, Anaconda Copper Mining Company, Sigma RHO, Mines football, Montana State University

The Amplifier - v. 2, no. 2

In this issue...Rocky Mountain Mineral Conference, M club, Halloween Dance, Carroll College, Martin Merkle Orchestra, Copper Guard, Forest Service, American Chemical Society

The Amplifier - v. 2, no. 5

In this issue...Lois Fordmeir, Library, Mineral Club, Mining Engineering, Dale Barnum, Geological Society, Dillon, Montana, Lewis and Clark Caverns, Montana Power Company

The Amplifier - v. 2, no. 7

In this issue...YMCA, Gardner Denver Scholarship, Civic Center, Butte, Montana, Air Force, Russell Dugdale, Debate team, Anderson Carlisle Society, Student Wives

The Amplifier - v. 2, no. 12

In this issue...Copper Guards, Vegas Club, Marcus Daly, Military Ball, Sigma RHO, Jersey Standard Oil, Joy Manufacturing Company, Smith Act, Dave Shepard

The Amplifier - v. 2, no. 15

In this issue...Yellowstone, Butte, Montana, Shamrock Picnic grounds, Carroll College, Butte Copper Baseball League, Civic Center, Dean McAuliffe

Structural model of the CopA copper ATPase of Enterococcus hirae based on chemical cross-linking

The CopA copper ATPase of Enterococcus hirae belongs to the family of heavy metal pumping CPx-type ATPases and shares 43% sequence similarity with the human Menkes and Wilson copper ATPases. Due to a lack of suitable protein crystals, only partial three-dimensional structures have so far been obtained for this family of ion pumps. We present a structural model of CopA derived by combining topological information obtained by intramolecular cross-linking with molecular modeling. Purified CopA was cross-linked with different bivalent reagents, followed by tryptic digestion and identification of cross-linked peptides by mass spectrometry. The structural proximity of tryptic fragments provided information about the structural arrangement of the hydrophilic protein domains, which was integrated into a three-dimensional model of CopA. Comparative modeling of CopA was guided by the sequence similarity to the calcium ATPase of the sarcoplasmic reticulum, Serca1, for which detailed structures are available. In addition, known partial structures of CPx-ATPase homologous to CopA were used as modeling templates. A docking approach was used to predict the orientation of the heavy metal binding domain of CopA relative to the core structure, which was verified by distance constraints derived from cross-links. The overall structural model of CopA resembles the Serca1 structure, but reveals distinctive features of CPx-type ATPases. A prominent feature is the positioning of the heavy metal binding domain. It features an orientation of the Cu binding ligands which is appropriate for the interaction with Cu-loaded metallochaperones in solution. Moreover, a novel model of the architecture of the intramembranous Cu binding sites could be derived.