Non-heme iron Dotaz Zobrazit nápovědu
In this minireview, we provide an account of the current state-of-the-art developments in the area of mono- and binuclear non-heme enzymes (NHFe and NHFe2) and the smaller NHFe(2) synthetic models, mostly from a theoretical and computational perspective. The sheer complexity, and at the same time the beauty, of the NHFe(2) world represents a challenge for experimental as well as theoretical methods. We emphasize that the concerted progress on both theoretical and experimental side is a conditio sine qua non for future understanding, exploration and utilization of the NHFe(2) systems. After briefly discussing the current challenges and advances in the computational methodology, we review the recent spectroscopic and computational studies of NHFe(2) enzymatic and inorganic systems and highlight the correlations between various experimental data (spectroscopic, kinetic, thermodynamic, electrochemical) and computations. Throughout, we attempt to keep in mind the most fascinating and attractive phenomenon in the NHFe(2) chemistry, which is the fact that despite the strong oxidative power of many reactive intermediates, the NHFe(2) enzymes perform catalysis with high selectivity. We conclude with our personal viewpoint and hope that further developments in quantum chemistry and especially in the field of multireference wave function methods are needed to have a solid theoretical basis for the NHFe(2) studies, mostly by providing benchmarking and calibration of the computationally efficient and easy-to-use DFT methods.
- MeSH
- kvantová teorie * MeSH
- lidé MeSH
- nehemové proteiny obsahující železo chemie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
Iron is a trace element that is vital for life. It is a component of innumerable hemoproteins and many essential non-heme iron proteins that are involved in oxygen binding and metabolism and electron transfer. Nevertheless, iron can also be toxic to cells as it catalyses the production of oxygen radicals. Iron uptake, transport, storage and utilization are therefore strictly regulated to meet the body's iron needs and to avoid its potential toxicity. Any imbalance in iron homeostasis may lead to the development of pathological conditions associated with either iron overload or iron deficiency. In this paper, we review the current understanding of iron biology with a focus on erythroid iron demand. In addition, we will discuss molecular pathophysiology with implications for novel therapies of selected hereditary defects of iron homeostasis.
- MeSH
- biologický transport MeSH
- deficit železa MeSH
- dietní železo farmakokinetika MeSH
- duodenum fyziologie MeSH
- enterocyty metabolismus MeSH
- erytroidní buňky metabolismus MeSH
- erytropoéza fyziologie MeSH
- hemoproteiny fyziologie MeSH
- homeostáza genetika fyziologie MeSH
- intestinální absorpce MeSH
- kationické antimikrobiální peptidy fyziologie MeSH
- kyslík krev metabolismus MeSH
- lidé MeSH
- makrofágy metabolismus MeSH
- myši knockoutované MeSH
- myši MeSH
- nehemové proteiny obsahující železo fyziologie MeSH
- přetížení železem metabolismus MeSH
- proteiny vázající železo fyziologie MeSH
- vrozené poruchy metabolismu kovů genetika metabolismus MeSH
- železo metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Duodenal biopsies are considered a suitable source of enterocytes for studies of dietary iron absorption. However, the expression level of molecules involved in iron absorption may vary along the length of duodenum. We aimed to determine whether the expression of molecules involved in the absorption of heme and non-heme iron differs depending on the location in the duodenum. Analysis was performed with samples of duodenal biopsies from 10 individuals with normal iron metabolism. Samples were collected at the following locations: (a) immediately post-bulbar, (b) 1-2 cm below the papilla of Vater and (c) in the distal duodenum. The gene expression was analyzed at the mRNA and protein level using real-time PCR and Western blot analysis. At the mRNA level, significantly different expression of HCP1, DMT1, ferroportin and Zip8 was found at individual positions of duodenum. Position-dependent expression of other molecules, especially of FLVCR1, HMOX1 and HMOX2 was also detected but with no statistical significances. At the protein level, we observed statistically significantly decreasing expression of transporters HCP1, FLVCR1, DMT1, ferroportin, Zip14 and Zip8 with advancing positions of duodenum. Our results are consistent with a gradient of diminishing iron absorption along the duodenum for both heme and non-heme iron.
- MeSH
- duodenum * metabolismus MeSH
- hem metabolismus MeSH
- iontový transport MeSH
- lidé MeSH
- messenger RNA genetika metabolismus MeSH
- železo * metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Publikační typ
- abstrakt z konference MeSH
Železo je prvek nezbytný pro život. Je součástí celé řady hemových i nehemových proteinů, které se účastní důležitých buněčných procesů, jako jsou např. vazba a metabolismus kyslíku nebo redoxní reakce. Nadbytek železa však může být pro buňku toxický, protože katalyzuje tvorbu kyslíkových radikálů. V organismu se proto vyvinul přísně regulovaný mechanismus příjmu, transportu a skladování železa, na kterém se podílí mnoho proteinů s vysoce specializovanou funkcí. Jejich úloha a význam byly odhaleny především na základě analýz myších modelů. Mezi nejvýznamnější objevy v této oblasti patří objasnění úlohy hepcidinu jako humorálního faktoru kontrolujícího homeostázu železa. Ucelenější obraz potom vznikl díky detailní analýze nálezů u pacientů postižených vrozenými poruchami homeostázy železa. Tyto patologické stavy jsou asociovány jak s nadbytkem, tak s nedostatkem železa.
Iron is an essential element indispensable for life. It is involved in oxygen transport and metabolism and redox reactions as a component of many essential hemoproteins and non-heme iron proteins. However, unbound iron can be toxic to the cell as it catalyses the production of oxygen radicals. Iron uptake, transport, storage and utilization are therefore strictly regulated to meet the body's iron needs and to avoid its potential toxicity. Analyses of mouse models and patients affected by inherited or acquired iron homeostasis defects have helped to identify crucial proteins involved in this process. One of the most important discoveries is the identification of hepcidin as a key regulator of iron homeostasis.
- Klíčová slova
- hepcidin, mikrocytární anémie,
- MeSH
- anemie z nedostatku železa diagnóza klasifikace terapie MeSH
- deficit železa MeSH
- diferenciální diagnóza MeSH
- financování organizované MeSH
- hemochromatóza diagnóza etiologie terapie MeSH
- hemosideróza diagnóza etiologie terapie MeSH
- homeostáza fyziologie genetika MeSH
- kationické antimikrobiální peptidy izolace a purifikace metabolismus MeSH
- lidé MeSH
- poruchy metabolismu železa diagnóza etiologie terapie MeSH
- přetížení železem diagnóza klasifikace terapie MeSH
- sideroblastická anemie diagnóza klasifikace terapie MeSH
- talasemie diagnóza etiologie terapie MeSH
- železo chemie metabolismus MeSH
- Check Tag
- lidé MeSH
The purpose of the study was to investigate the expression of ferroportin protein following treatments that affect systemic hepcidin. Administration of erythropoietin to C57BL/6J mice decreased systemic hepcidin expression; it also increased heart ferroportin protein content, determined by immunoblot in the membrane fraction, to approximately 200% of control values. This increase in heart ferroportin protein is very probably caused by a decrease in systemic hepcidin expression, in accordance with the classical regulation of ferroportin by hepcidin. However, the control of heart ferroportin protein by systemic hepcidin could apparently be overridden by changes in heart non-heme iron content since injection of ferric carboxymaltose to mice at 300 mg Fe/kg resulted in an increase in liver hepcidin expression, heart non-heme iron content, and also a threefold increase in heart ferroportin protein content. In a separate experiment, feeding an iron-deficient diet to young Wistar rats dramatically decreased liver hepcidin expression, while heart non-heme iron content and heart ferroportin protein content decreased to 50% of controls. It is, therefore, suggested that heart ferroportin protein is regulated primarily by the iron regulatory protein/iron-responsive element system and that the regulation of heart ferroportin by the hepcidin-ferroportin axis plays a secondary role.
Závěrečná zpráva o řešení grantu Interní grantové agentury MZ ČR
Přeruš. str. : tab., grafy ; 32 cm
In vitro utilization of haem and non-haem iron by Giardia intestinalis, the effect of iron deficiency on Giardia metabolism and the possible effect of Giardia on iron absorption by enterocytes using cultured intestinal cell line Caco -2 will be studied.
Projekt řeší zužitkovatelnost komplexů hemového a nehemového železa buňkami Giardia intestinalis, vliv nedostatku železa na metabolismus parazita a možný vliv parazita na vstřebávání železa enterocyty v modelovém systému in vitro.
- MeSH
- ferritin metabolismus MeSH
- Giardia lamblia metabolismus růst a vývoj MeSH
- nehemové proteiny obsahující železo MeSH
- železo metabolismus MeSH
- Konspekt
- Patologie. Klinická medicína
- NLK Obory
- parazitologie
- hematologie a transfuzní lékařství
- NLK Publikační typ
- závěrečné zprávy o řešení grantu IGA MZ ČR
