519 resultados para Catabolismo de heme


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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

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Vertebrate hemoglobin, contained in erythrocytes, is a globular protein with a quaternary structure composed of 4 globin chains (2 alpha and 2 beta) and a prosthetic group named heme bound to each one. Having myoglobin as an ancestor, hemoglobin acquired the capacity to respond to chemical stimuli that modulate its function according to tissue requirements for oxygen. Fish are generally submitted to spatial and temporal O2 variations and have developed anatomical, physiological and biochemical strategies to adapt to the changing environmental gas availability. Structurally, most fish hemoglobins are tetrameric; however, those from some species such as lamprey and hagfish dissociate, being monomeric when oxygenated and oligomeric when deoxygenated. Fish blood frequently possesses several hemoglobins; the primary origin of this finding lies in the polymorphism that occurs in the globin loci, an aspect that may occasionally confer advantages to its carriers or even be a harmless evolutionary remnant. on the other hand, the functional properties exhibit different behaviors, ranging from a total absence of responses to allosteric regulation to drastic ones, such as the Root effect.

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Enzimas Peroxidases são heme-proteínas encontradas nos diferentes organismos vivos, especialmente vegetais, apresentam importante papel fisiológico/bioquímico como proteção contra microorganismos invasores. A soja, um dos mais importantes produtos para o agronegócio brasileiro apresenta na casca de suas sementes (subproduto) alta atividade de peroxidase, denominada soybean peroxidase,com potencial de utilização em métodos analíticos clínicos. A proposta do trabalho foi aplicar o planejamento fatorial para otimização das condições extração da enzima, definição das condições ótimas de atividade (pH e temperatura), utilizando metodologia de superfície de resposta. Os dados obtidos com clara definição foram: i) extração em pó cetonico, ii) meio reacional: pH 3,3, volume da amostra contendo a enzima 330 µL - 340 µL, peróxido de hidrogênio 4,2 mmol.L-1 150 µL, tempo de reação 20 segundos, temperatura 50º C, substrato guaiacol 30mmol.L-1 300 µL, e 0,1 mol.L-1 de NaCl. O uso da dessa metodologia para definição das condições de extração e estudos cinético-enzimáticos da peroxidase de soja foram eficientes e mais precisos, comparado a metodologia de variações/repetições (tentativa e erro).

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5-Aminolevulinic acid (ALA), a heme precursor that accumulates in acute intermittent porphyria patients and lead-exposed individuals, has previously been shown to autoxidize with generation of reactive oxygen species and to cause in vitro oxidative damage to rat liver mitochondria. We now demonstrate that chronically ALA-treated rats (40 mg/kg body wt every 2 days for 15 days) exhibit decreased mitochondrial enzymatic activities (superoxide dismutase, citrate synthase) in liver and soleus (type I, red) and gastrocnemius (type IIb, white) muscle fibers. Previous adaptation of rats to endurance exercise, indicated by augmented (cytosolic) CuZn-superoxide dismutase (SOD) and (mitochondrial) Mn-SOD activities in several organs, does not protect the animals against liver and soleus mitochondrial damage promoted by intraperitoneal injections of ALA. This is suggested by loss of citrate synthase and Mn-SOD activities and elevation of serum lactate levels, concomitant to decreased glycogen content in soleus and the red portion of gastrocnemius (type IIa) fibers of both sedentary and swimming-trained ALA-treated rats. In parallel, the type IIb gastrocnemius fibers, which are known to obtain energy mainly by glycolysis, do not undergo these biochemical changes. Consistently, ALA-treated rats under swimming training reach fatigue significantly earlier than the control group. These results indicate that ALA may be an important prooxidant in vivo.

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Background. Iron-deficiency anemia currently is the most frequently occurring nutritional disorder worldwide. Previous Brazilian studies have demonstrated that drinking water fortified with iron and ascorbic acid is an adequate vehicle for improving the iron supply for children frequenting day-care centers. Objective. The objective of this study was to clarify the role of ascorbic acid as a vehicle for improving iron intake in children in day-care centers in Brazil. Methods. A six-month study was conducted on 150 children frequenting six day-care centers divided into two groups of three day-care centers by drawing lots: the iron-C group (3 day-care centers, n = 74), which used water fortified with 10 mg elemental iron and 100 mg ascorbic acid per liter, and the comparison group (3 day-care centers, n = 76), which used water containing only 100 mg ascorbic acid per liter. Anthropometric measurements and determinations of capillary hemoglobin were performed at the beginning of the study and after six months of intervention. The food offered at the day-care centers was also analyzed. Results. The fo od offered at the day-care center was found to be deficient in ascorbic acid, poor in heme iron, and adequate in non-heme iron. Supplementation with fortified drinking water resulted in a decrease in the prevalence of anemia and an increase in mean hemoglobin levels associated with height gain in both groups. Conclusions. Fortification of drinking water with iron has previously demonstrated effectiveness in increasing iron supplies. This simple strategy was confirmed in the present study. The present study also demonstrated that for populations receiving an abundant supply of non-heme iron, it is possible to control anemia in a simple, safe, and inexpensive manner by adding ascorbic acid to drinking water. © 2005, The United Nations University.

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Background: Hematophagous insects digest large amounts of host hemoglobin and release heme inside their guts. In Rhodnius prolixus, hemoglobin-derived heme is detoxified by biomineralization, forming hemozoin (Hz). Recently, the involvement of the R. prolixus perimicrovillar membranes in Hz formation was demonstrated. Methodology/Principal Findings: Hz formation activity of an α-glucosidase was investigated. Hz formation was inhibited by specific α-glucosidase inhibitors. Moreover, Hz formation was sensitive to inhibition by Diethypyrocarbonate, suggesting a critical role of histidine residues in enzyme activity. Additionally, a polyclonal antibody raised against a phytophagous insect α-glucosidase was able to inhibit Hz formation. The α-glucosidase inhibitors have had no effects when used 10 h after the start of reaction, suggesting that α-glucosidase should act in the nucleation step of Hz formation. Hz formation was seen to be dependent on the substrate-binding site of enzyme, in a way that maltose, an enzyme substrate, blocks such activity. dsRNA, constructed using the sequence of α-glucosidase gene, was injected into R. prolixus females' hemocoel. Gene silencing was accomplished by reduction of both α-glucosidase and Hz formation activities. Insects were fed on plasma or hemin-enriched plasma and gene expression and activity of α-glucosidase were higher in the plasma plus hemin-fed insects. The deduced amino acid sequence of α-glucosidase shows a high similarity to the insect α-glucosidases, with critical histidine and aspartic residues conserved among the enzymes. Conclusions/Significance: Herein the Hz formation is shown to be associated to an a-glucosidase, the biochemical marker from Hemipteran perimicrovillar membranes. Usually, these enzymes catalyze the hydrolysis of glycosidic bond. The results strongly suggest that α-glucosidase is responsible for Hz nucleation in the R. prolixus midgut, indicating that the plasticity of this enzyme may play an important role in conferring fitness to hemipteran hematophagy, for instance. © 2009 Mury et al.

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Mammals keep their body temperature (Tb) relatively constant even under a wide range of ambient temperature variation. However, in some particular situations it may be beneficial to increase or to decrease Tb. For instance, under hypoxic conditions, a regulated drop in Tb (anapyrexia) takes place which has been reported to be crucial for survival in a number of different species. This review highlights major advances in the research about nitric oxide (NO) and carbon monoxide (CO-where data are relatively less abundant), before focusing on the role played by these gaseous neuromediators in thermoregulation, under the conditions of euthermia and anapyrexia. Available data are consistent with the notion that both NO and CO, acting on the CNS, participate in thermoregulation, with NO decreasing Tb and CO increasing it. However further studies are required before definitive conclusions can be made as to their physiological mechanisms of action.

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Vampire bats are notorious for being the sole mammals that strictly feed on fresh blood for their survival. While their saliva has been historically associated with anticoagulants, only one antihemostatic (plasminogen activator) has been molecularly and functionally characterized. Here, RNAs from both principal and accessory submaxillary (submandibular) salivary glands of Desmodus rotundus were extracted, and ~. 200. million reads were sequenced by Illumina. The principal gland was enriched with plasminogen activators with fibrinolytic properties, members of lipocalin and secretoglobin families, which bind prohemostatic prostaglandins, and endonucleases, which cleave neutrophil-derived procoagulant NETs. Anticoagulant (tissue factor pathway inhibitor, TFPI), vasodilators (PACAP and C-natriuretic peptide), and metalloproteases (ADAMTS-1) were also abundantly expressed. Members of the TSG-6 (anti-inflammatory), antigen 5/CRISP, and CCL28-like (antimicrobial) protein families were also sequenced. Apyrases (which remove platelet agonist ADP), phosphatases (which degrade procoagulant polyphosphates), and sphingomyelinase were found at lower transcriptional levels. Accessory glands were enriched with antimicrobials (lysozyme, defensin, lactotransferrin) and protease inhibitors (TIL-domain, cystatin, Kazal). Mucins, heme-oxygenase, and IgG chains were present in both glands. Proteome analysis by nano LC-MS/MS confirmed that several transcripts are expressed in the glands. The database presented herein is accessible online at http://exon.niaid.nih.gov/transcriptome/D_rotundus/Supplemental-web.xlsx. These results reveal that bat saliva emerges as a novel source of modulators of vascular biology. Biological significance: Vampire bat saliva emerges as a novel source of antihemostatics which modulate several aspects of vascular biology. © 2013.

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Pós-graduação em Genética - IBILCE

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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

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Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)