Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P02794 (ferritin)
 17,525 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Protein ferroxidase site(s), which catalyze the reaction between ferrous ion and dioxygen, have long been thought to play a role in core formation in ferritin; however, the mechanism of the reaction has never been studied in detail. In the present work, the enzymatic activity of ferritin was examined using oximetry, the net Fe2+ oxidation reaction being as follows. [formula: see text] The reaction exhibits saturation kinetics with respect to both Fe2+ and O2 (apparent Michaelis constants: Km,Fe = 0.35 +/- 0.01 mM and Km,O2 = 0.14 +/- 0.03 mM). The enzyme has a turnover number kcat = 80 +/- 3 min-1 at 20 degrees C with maximal activity at pH 7. The kinetics are discussed in terms of two mechanisms, one involving monomeric and the other dimeric iron protein complexes. In both instances Fe(II) oxidation occurs in 1-electron steps. Zinc(II) is a competitive inhibitor of iron(II) oxidation at Zn2+/apoprotein ratios > or = 6 (inhibitor constant KI,Zn = 0.067 +/- 0.011 mM) but appears to be a noncompetitive inhibitor at lower ratios (< or = 2), indicating the presence of more than one type of zinc binding site on the protein. At increments of 50 Fe2+/protein or less, all of the iron is oxidized via the protein ferroxidase site(s), independent of the amount of core already present. However, when larger increments are employed, some iron oxidation appears to occur on the surface of the mineral core. The results of these studies emphasize the role of the protein shell in all phases of core growth and confirm the presence of a functionally important catalytic site in ferritin in addition to other binding sites on the protein for iron.
J Biol Chem 1992 Dec 15
PMID:Ferroxidase kinetics of horse spleen apoferritin. 146 15

Current concepts as to the cause of Parkinson's disease (PD) suggest an inherited predisposition to environmental or endogenous toxic agents. Study of the substantia nigra after death in PD has highlighted three major changes: (1) evidence of oxidative stress and depletion of reduced glutathione; (2) high levels of total iron, with reduced ferritin buffering; and (3) mitochondrial complex I deficiency. Which of these is the primary event, generating a secondary cascade of changes culminating in nigral cell death, is unknown. In presymptomatic Lewy body-positive control brains, the nigra shows depletion of reduced glutathione content and, possibly, a reduction of complex I activity. Whatever the significance of these various abnormalities, be they causal or secondary, they provide novel targets for the development of new strategies to treat the cause of PD.
Neurology 1992 Dec
PMID:New insights into the cause of Parkinson's disease. 146 74

The ability to incorporate iron in vitro was studied in homopolymers of human ferritin L-chain, human ferritin H-chain and its variants and in homopolymer mixtures. The H-chain variants carried amino acid substitutions in the ferroxidase centre and/or in carboxy residues on the cavity surface. Iron incorporation was examined by gel electrophoresis of the reaction products by staining for iron and protein. It was found that inactivation of the ferroxidase centre combined with the substitution of four carboxy groups on the cavity abolished the ability of H-chain ferritin to incorporate iron. Competition experiments with limited amounts of iron showed that, at neutral pH, L-chain ferritin is more efficient in forming iron cores than the H-chain variants altered at the ferroxidase activity or in the cavity. Competition experiments at pH 5.5 demonstrated that L-chain apoferritin is able to incorporate iron only when in the presence of H-chain variants with ferroxidase activity. The results indicate that L-chain apoferritin has a higher capacity than the H-chain apoferritin to induce iron-core nucleation, whereas H-chain ferritin is superior in promoting Fe(II) oxidation. The finding of cooperative roles of the H- and L-chains in ferritin iron uptake provides a clue to understanding the biological function of isoferritins.
Biochem J 1992 Dec 01
PMID:Evidence of H- and L-chains have co-operative roles in the iron-uptake mechanism of human ferritin. 146 63

Superoxide and hydrogen peroxide are reactive oxygen species (ROS) primarily produced by phagocytic cells as a consequence of the process of phagocytosis. This defensive role, may, however, become one of attack when production of ROS is excessive and overwhelms cellular scavenging systems. This happens in situations such as acute inflammation and results in host cell membrane damage, which is particularly prevalent in the presence of transition metal catalysts such as iron and copper. The skin is uniquely vulnerable to this attack being rich in polyunsaturated fatty acids and exposed to high oxygen tensions and ultraviolet light, both of which promote production of ROS. Additionally, the respiratory burst of infiltrating polymorphonuclear leukocytes and macrophages in inflamed skin will produce high local levels of superoxide that can release "catalytic iron" from storage proteins such as ferritin. The role of iron and ROS in the pathogenesis of inflammatory skin disease is discussed as is the possibility of novel therapeutic strategies based on their removal.
J Invest Dermatol 1992 Dec
PMID:Skin inflammation: reactive oxygen species and the role of iron. 146 83

Oxidant stress, due to the formation of hydrogen peroxide and oxygen-derived free radicals, can cause cell damage due to chain reactions of membrane lipid peroxidation. Because the substantia nigra is rich in dopamine, which can undergo both enzymatic oxidation via monoamine oxidase and nonenzymatic autoxidation, hydrogen peroxide and oxyradicals (superoxide anion radical and hydroxyl radical) are generated in this midbrain nucleus. Although proof that oxidant stress actually causes the loss of monoaminergic neurons in patients with Parkinson's disease is lacking, there is a considerable body of evidence from studies in both animals and humans that support the concept. (1) Neurotoxins that selectively destroy the dopaminergic neurons in the nigra, such as 6-hydroxydopamine and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), appear to act via oxidant stress. (2) The substantia nigra of patients with Parkinson's disease reveals evidence of oxidant stress by the findings of increased lipid peroxidation and decreased reduced glutathione. (3) Total iron is increased and ferritin is reduced in the substantia nigra pars compacta in patients with Parkinson's disease. This combination suggests that this transition metal is in a low molecular weight form, capable of catalyzing nonenzymatic oxidative reactions, especially the conversion of hydrogen peroxide to hydroxyl radical, which is the most reactive of the oxygen radicals. (4) Neuromelanin, a product of dopamine autoxidation, can serve as a reservoir for iron, promoting the generation of oxyradicals. (5) Antioxidant defense mechanisms appear to be reduced in the parkinsonian substantia nigra with the findings of decreased activities of glutathione peroxidase and catalase.(ABSTRACT TRUNCATED AT 250 WORDS)
Ann Neurol 1992 Dec
PMID:The oxidant stress hypothesis in Parkinson's disease: evidence supporting it. 147 73

The iron storage protein, ferritin, is widely distributed in the living kingdom. Here the complete cDNA and derived amino-acid sequence of pea seed ferritin are described, together with its predicted secondary structure, namely a four-helix-bundle fold similar to those of mammalian ferritins, with a fifth short helix at the C-terminus. An N-terminal extension of 71 residues contains a transit peptide (first 47 residues) responsible for plastid targetting as in other plant ferritins, and this is cleaved before assembly. The second part of the extension (24 residues) belongs to the mature subunit; it is cleaved during germination. The amino-acid sequence of pea seed ferritin is aligned with those of other ferritins (49% amino-acid identity with H-chains and 40% with L-chains of human liver ferritin in the aligned region). A three-dimensional model has been constructed by fitting the aligned sequence to the coordinates of human H-chains, with appropriate modifications. A folded conformation with an 11-residue helix is predicted for the N-terminal extension. As in mammalian ferritins, 24 subunits assemble into a hollow shell. In pea seed ferritin, its N-terminal extension is exposed on the outside surface of the shell. Within each pea subunit is a ferroxidase centre resembling those of human ferritin H-chains except for a replacement of Glu-62 by His. The channel at the 4-fold-symmetry axes defined by E-helices, is predicted to be hydrophilic in plant ferritins, whereas it is hydrophobic in mammalian ferritins.
Biochem J 1992 Dec 15
PMID:Amino-acid sequence and predicted three-dimensional structure of pea seed (Pisum sativum) ferritin. 147 6

Six of 14 patients with acute myeloblastic leukemia (AML) complicated reactive histiocytosis during initial remission induction therapy. All six patients had a high fever without signs of infection during initial chemotherapy, and periods of myelosuppression were prolonged. Histiocytes with a mature appearance, some of which phagocyted erythrocytes, thrombocytes or neutrophils, increased in the bone marrow. All of 3 patients tested showed high serum levels of ferritin. Two of 3 patients treated with 125 mg/day methylprednisolone achieved complete remission. In the remaining 3 patients, one patient achieved complete remission, but the others died of fungal pneumonia or sepsis. Thus, reactive histiocytosis is one of the severe complications in patients with AML undergoing chemotherapy.
Rinsho Ketsueki 1992 Dec
PMID:[Reactive histiocytosis during initial remission induction therapy for acute myeloblastic leukemia]. 147 93

This study was undertaken to determine tissue and serum ferritin levels in different stages of breast carcinoma. Eighty-nine cases have been evaluated, the groups investigated being breast carcinoma, benign breast disease and healthy controls. Ferritin levels in both the sera and the tissue cytosols were measured by an enzyme immunoassay method, while total proteins were assayed by Lowry's procedure and the ferritin concentrations given in ng ferritin/mg cytosol protein. No significant difference has been determined for serum ferritin between any of the groups studied, while the tissue cytosol ferritins were found to be 91.6 +/- 50.9, 565.0 +/- 48.3, 142.7 +/- 93.3, 683.3 +/- 212.9 and 655.5 +/- 100.4 ng/mg cytosol protein for the benign, malign (global), malign (stage I), malign (stage II) and malign (stage III) groups, respectively. The differences between the malign groups and the benign group were found to be highly significant (P < 0.001) except for the stage I subgroup, which was fairly significant (P < 0.05). A sensitivity of 90% was evaluated for tissue cytosol ferritin in breast carcinoma, the 'intra-patient' sensitivity being 100%. In conclusion, we state that tissue ferritin is more valuable than serum ferritin as a tumour marker of diagnosis for breast carcinoma.
Cancer Lett 1992 Dec 24
PMID:Cytosol and serum ferritin in breast carcinoma. 148 58

Nutritional status was assessed in a group of patients with Parkinson's disease. Weight loss since the onset of disease occurred in 52% of the patients and 22% had lost more than 12.8 kg. Although 67% of patients experienced eating difficulties of some kind, dietary intakes of protein and energy were not significantly lower than recommended intakes. Plasma levels of albumin (44.2 g/l vs 45.7 g/l), vitamin A (2.61 vs 2.94 mumol/l), vitamin E (22.0 vs 32.0 mumol/l), iron (15.3 vs 18.3 mumol/l) and zinc (14.2 vs 18.7 mumol/l) were significantly lower (P < 0.05) in the patients than in healthy controls. Levels of ferritin, total iron-binding capacity and copper were similar between groups. The potential significance of low levels of vitamin E and zinc are discussed in relation to oxidative stress in the pathogenesis of this disease.
Eur J Clin Nutr 1992 Dec
PMID:Diet, body size and micronutrient status in Parkinson's disease. 148 17

Measurements of nutritionally relevant biochemical and endocrine variables were made on 60 apparently healthy children (group A) whose parents suffered from leprosy and who had been separated at the age of 4 years and brought up in preventoria. Most of the measurements were also made on a comparison group of healthy children from the same poor socio-economic class (group B). In both groups the serum concentrations of cholesterol and triglycerides were well below those found in Western populations. Almost all the children in both groups were anaemic, but serum iron and ferritin levels were satisfactory. Folate and vitamin B12 levels were measured in group A only and were low in a significant proportion. Deficiency of these water-soluble vitamins may be a cause of the anaemia. Low albumin levels were found in 40% of group A children, compared with 2% in group B. The concentrations of calcium and magnesium were lower and that of phosphate higher in group A than in B. In both groups one-third of the children had low levels of serum zinc. Fifteen per cent of group A children had biochemical evidence of vitamin A deficiency, but none were deficient in vitamin E. Levels of total T3 and total T4 were below the lower limit of normal in a substantial proportion of children in both groups. Concentrations of parathyroid hormone were increased in parallel with the low values for serum calcium. Radiological studies of ossification centres in 57 group A children showed delayed maturation in 11 cases. The relevance of these findings to previous studies of the children of lepers in India is discussed.
Eur J Clin Nutr 1992 Dec
PMID:Nutritional status of children of urban leprosy patients staying at preventoria based on biochemical parameters. 148 18


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