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Electron Paramagnetic Resonance of Copper Proteins
Published in René Lontie, Copper Proteins and Copper Enzymes, 1984
In general, copper proteins in their native state may contain either or both copper(I) or copper(II). Since copper(I) is not a paramagnetic ion, this form will only concern us in passing in this review. However, the copper(II) ion is paramagnetic and should give an EPR signal. The copper(II) ions in proteins have been broadly classified as type 1, type 2, and type 3 on the basis of their EPR signals, and this classification has been reviewed recently by Fee3 and Boas et al.4 Type 1 and type 2 are distinguished by their EPR spectral behavior, while type 3 does not give an EPR signal in the native state for reasons which we discuss below. Appendix 1 lists some of the naturally occurring copper proteins and gives representative values of the g and hyperfine parameters associated with their EPR spectra.
Determination of ultra-trace metal-protein interactions in co-formulated monoclonal antibody drug product by SEC-ICP-MS
Published in mAbs, 2023
Laurence Whitty-Léveillé, Zachary L. VanAernum, Jorge Alexander Pavon, Christa Murphy, Katie Neal, William Forest, Xinliu Gao, Wendy Zhong, Douglas D. Richardson, Hillary A. Schuessler
During our analysis, we observed an artificially high peak area at t = 0 sample in the copper chromatograms in the free copper region (~5.5 min), as depicted in Figure 4a. Further study suggested that the presence of histidine in the formulation buffer resulted in copper ions leaching from the HPLC system. Indeed, among the amino acids, L-histidine is one of the strongest copper-chelating ligands, as demonstrated by Deschamps and coworkers.50 Prior to the addition of a wash step, the peak area of copper did not correlate with the total copper content obtained by bulk ICP-MS/MS analysis (Table 1), with the highest peak area being for t = 0 sample (Figure 4a). As samples were injected, the peak area decreased, indicating that less copper was stripped from the HPLC components as the system was continuously flushed with mobile phase. In an attempt to counteract this phenomenon, we added an L-histidine washing step before and between runs to remove any contribution of copper leaching from the instrument. The implementation of the histidine wash step solved this issue and generated results that agreed with the trends observed by bulk ICP-MS/MS analysis (Table 1), as illustrated in Figure 4b. It was then possible to observe that the copper-protein interaction peak area increased from t = 0 to 5 days in the mAb eluting range and further stabilized after 5 days. Similar to chromium, cobalt and nickel, a peak increase for copper was detected in the free metal species region at the later eluting range.
Novel compound heterozygous PANK2 gene mutations in a Chinese patient with atypical pantothenate kinase-associated neurodegeneration
Published in International Journal of Neuroscience, 2018
Yuan Cheng, Yu-tao Liu, Zhi-hua Yang, Jing Yang, Chang-he Shi, Yu-ming Xu
The proband was a 26-year-old male with only mild symptoms. At the age of 25 years, he developed a progressive prosopospasm and slurred speech. The patient’s tongue movement was markedly slow and he had a right-deflected staphyle. Limb reflexes were brisk and gait was stiff, with the patient tending to walk on his toes. The patient’s cognition appeared normal. Laboratory testing revealed low levels of copper-protein, globulin and total protein, and increased alanine aminotransferase. Remaining physical and laboratory examinations showed normal results. T2-weighted brain MRI showed a characteristic eye-of-the-tiger sign (Figure 1). The patient’s father and mother were not consanguineous (Figure 2). They were healthy and did not exhibit gait difficulty or dysarthria. The biochemistry, haematology, and clinical features of the parents and sister were normal.
Iron and manganese-related CNS toxicity: mechanisms, diagnosis and treatment
Published in Expert Review of Neurotherapeutics, 2019
Pan Chen, Melissa Totten, Ziyan Zhang, Hana Bucinca, Keith Erikson, Abel Santamaría, Aaron B. Bowman, Michael Aschner
Iron is the second most abundant metal on the earth crust, while manganese is the fifth. They both are transition metals and have similar characteristics and functions. For example, they share similar brain distribution and common cellular transporters, including divalent metal transporter 1 (DMT1) [1], the transferrin (Tf)/transferrin receptor (TfR) system [2–5] and the Fe exporter, Ferroportin (Fpn) [6]. They are essential cofactors for many proteins involved in the normal function of the brain. Fe is critical for oxygen transport, storage and activation, electron transport, DNA synthesis, mitochondrial respiration, myelin synthesis, neurotransmitter synthesis and metabolism [7–9]. Mn plays important roles in antioxidant defense, energy production, immune response and regulation of neuronal activities [10–12]. Ingestion is the primary route for Fe and Mn uptake [9,10]. In adults, approximately 1–2 mg of Fe [13] and 1.8–2.3 mg of Mn [10] are absorbed daily. The systemic absorption of Fe takes place in the lumen of the small intestine through enterocytes [14]. After absorption by enterocytes, Fe interacts with transporter proteins, such as Tf/TfR and iron regulatory proteins (IRPs), and enters blood stream [8,9,15]. The brain-iron intake process involves multiple steps and is similar to Fe intake of enterocytes in the small intestine. The Tf/TfR system plays an important role in brain Fe uptake, which facilitates Fe transport across the blood-brain barrier (BBB) and neurons [14,16]. Astrocytes have a pivotal role in the regulation of Fe homeostasis, acquiring Fe by DMT1 [14,16]. Ferroportin mediates Fe export in neurons, while ceruloplasmin plays an important role in astrocytes. As a copper protein, ceruloplasmin can oxidize Fe (II) to Fe (III) and its deficiency leads to neurodegeneration secondary to Fe accumulation [16]. Mn shares similar transport mechanisms to Fe, except IRP [10,12].