Electron Paramagnetic Resonance of Copper Proteins
René Lontie in 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.
Copper Metabolism and Diseases of Copper Metabolism
René Lontie in Copper Proteins and Copper Enzymes, 1984
While virtually nothing is known about copper proteins in cellular organelles other than the properties of mitochondrial cytochrome c oxidase, cytosolic copper proteins have been the subject of several investigations. The major cytoplasmic copper protein of the resting liver and most other organs is the Cu/Zn-SOD; mammalian mitochondria contain relatively high concentrations of the Mn-SOD.160,161 In the kidney, metallothionein predominates (vide infra). SOD enzymes are ubiquitous and have protective functions in catalysing the dismutation of superoxide radical, an intermediate of many enzymatic reactions involving oxygen.160,161 The predicted toxicity of intracellular and the precise physiologic role of SOD are still being considered.162
Antioxidant Activity of Ceruloplasmin
Robert A. Greenwald in CRC Handbook of Methods for Oxygen Radical Research, 2018
Ceruloplasmin is the major copper-containing protein of extracellular fluids. It has a molecular weight of approximately 134,000 with six or seven copper ions per molecule. Six of these coppers are tightly bound to ceruloplasmin and can only be released at low pH in the presence of a reducing agent. However, ceruloplasmin may be able to supply copper within cells for incorporation into other copper proteins such as superoxide dismutase (SOD) or cytochrome oxidase.1,2 This copper-donor role is sometimes referred to as a copper “transport” function. However, ceruloplasmin does not specifically bind and transport loosely bound copper in the way that transferrin binds and transports iron.
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.
Histidine residues at the copper-binding site in human tyrosinase are essential for its catalytic activities
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Hyangsoon Noh, Sung Jun Lee, Hyun-Joo Jo, Hye Won Choi, Sungguan Hong, Kwang-Hoon Kong
Melanin biosynthesis is a complicated pathway involving chemical and enzymatic reactions and is limited to melanocytes in mammals. Tyrosinase (monophenol monooxygenase, EC 1.14.18.1) plays a pivotal role in the melanin synthesis pathway. Moreover, tyrosinase is the only human melanogenic enzyme with well-established in vivo catalytic enzyme activity1, catalysing several steps in melanin synthesis and generated by the hydroxylation of l-tyrosine2–4. Tyrosinase is a copper-containing metalloprotein belonging to the type-3 copper protein family, together with haemocyanins and catechol oxidases. These proteins are abundant in mammals, bacteria, fungi, and plants, and the active sites are highly conserved among the different species5. By synthesising melanin, tyrosinase exerts a protective function in UV-induced damage6 but can also cause hyperpigmentation, leading to aesthetic problems and melanoma. Moreover, the lack of tyrosinase activity is associated with oculocutaneous albinism (OCA) in many animal species, including humans7,8. As such, human tyrosinase is a quite attractive target for medical and industrial applications. Particularly, the screening of potent antagonists of tyrosinase and their subsequent development to drugs have attracted substantial interest in the cosmetic industry.
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].
Related Knowledge Centers
- Copper
- Cysteine
- Cytochrome C Oxidase
- Electron Transfer
- Histidine
- Oxygen
- Prosthetic Group
- Protein
- Adenosine Triphosphate
- Trigonal Planar Molecular Geometry