Aminokyseliny jsou molekuly obsahující aminoskupinu (-NH2), karboxylovou skupinu (-COOH) a postranní řetězec. Aminokyseliny hrají ústřední roli jako stavební bloky proteinů i jako intermediáty metabolismu. Dvacet aminokyselin nalezených v proteinech je nositelem jejich obrovské chemické rozmanitosti. Přírodní aminokyseliny v proteinech jsou alfa-aminokyseliny, tzn. že jejich aminoskupina je lokalizována na uhlíku v blízkosti karboxylové skupiny, označované jako pozice alfa. Existují však aminokyseliny, jejichž aminoskupina je lokalizována na vzdálenějších uhlících: beta, gama atd. Takovou aminokyselinou je i beta-alanin. Beta-alanin je přírodní aminokyselina, která však není využívána při biosyntéze žádných důležitých proteinů a enzymů. Přesto je beta-alanin nejrozšířenější beta-aminokyselinou. Byl nalezen u živočichů, rostlin, hub i bakterií, neboť je zabudován do látek jejich primárního i sekundárního metabolismu. U savců je beta-alanin součástí přirozeně se vyskytujících dipeptidů karnosinu a anserinu, které jsou důležitými molekulami jejich primárního metabolismu, a také kyseliny pantotenové (vitamin B5), která sama je součástí koenzymu A. Některé sekundární metabolity beta-alaninu jsou biologicky velmi aktivní sloučeniny, které byly nejprve nalezeny v rostlinách a suchozemských bakteriích a později, počínaje rokem 1980, v mořských houbách a cyanobakteriích (sinicích), které se staly významným předmětem výzkumu. Tyto organismy velmi často obsahují cyklické a acyklické peptidy a depsipeptidy s neobvyklými aminokyselinani. Přírodní látky se zabudovaným beta-alaninem představují substance zajímající jak akademické, tak průmyslové chemiky, farmakology a toxikology. Neobyčejně významné jsou tyto látky pro všechny, kteří se zajímají o bioorganickou a biologickou chemii.

Amino acids are molecules having amino groups (-NH2), carboxylic groups (-COOH) and side chains. Amino acids play a central role as structural blocks of proteins and as intermediate metabolism products. Twenty amino acids present in proteins are carriers of their enormous chemical diversity. Natural amino acids in proteins are alpha-amino acids, which means that their amino group is located at the carbon atom bearing the carboxylic group, referred to as alpha position. However, there are also amino acids, whose amino group is located at more distant carbon atoms: beta, gamma, etc. This type of amino acid is also beta-alanine. Beta-alanine is a natural amino acid, which is, however, not used in the biosynthesis of important proteins and enzymes. In spite of this, betaalanine is the most frequently occurring beta-amino acid. It was found in animals, plants, fungi and bacteria, since it is incorporated into substances of their primary and secondary metabolism. In mammals, beta-alanine is a part of natural dipeptides carnosine and anserine, which are important molecules in their primary metabolism and also in pantothenic acid (vitamin B5), which is a part of coenzyme A. Certain secondary metabolites of beta-alanine are biologically highly active compounds, which were first found in fungi and terrestrial bacteria and later, starting from 1980, in sponges and cyanobacteria, which became considerable subjects of research. These organisms very frequently contain cyclic and acyclic peptides and depsipeptides with unusual amino acids. Natural compounds with incorporated beta-alanine are substances, which are of interest to academic as well as industrial chemists, pharmacologists and toxicologists. These substances

• MeSH
• alanin analogy a deriváty   biosyntéza   metabolismus   MeSH
• aminokyseliny metabolismus   škodlivé účinky   terapeutické užití   MeSH
• anserin metabolismus   terapeutické užití   MeSH
• cyklické peptidy farmakologie   metabolismus   terapeutické užití   MeSH
• depsipeptidy farmakologie   metabolismus   terapeutické užití   farmakologie   metabolismus   terapeutické užití   MeSH
• karnosin farmakologie   metabolismus   terapeutické užití   MeSH
• neurotoxiny metabolismus   otrava   škodlivé účinky   MeSH
• peptidy farmakologie   metabolismus   terapeutické užití   MeSH
• příroda MeSH
• rostliny metabolismus   otrava   MeSH
• sinice chemie   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH

Mycotoxins are secondary metabolites produced by several species of fungi, including the Fusarium, Aspergillus, and Penicillium species. Currently, more than 300 structurally diverse mycotoxins are known, including a group called minor mycotoxins, namely enniatins, beauvericin, and fusaproliferin. Beauvericin and enniatins possess a variety of biological activities. Their antimicrobial, antibiotic, or ionoforic activities have been proven and according to various bioassays, they are believed to be toxic. They are mainly found in cereal grains and their products, but they have also been detected in forage feedstuff. Mycotoxins in feedstuffs of livestock animals are of dual concern. First one relates to the safety of animal-derived food. Based on the available data, the carry-over of minor mycotoxins from feed to edible animal tissues is possible. The second concern relates to detrimental effects of mycotoxins on animal health and performance. This review aims to summarize current knowledge on the relation of minor mycotoxins to livestock animals.

• MeSH
• depsipeptidy toxicita   MeSH
• dobytek MeSH
• jedlá semena toxicita   MeSH
• kontaminace potravin analýza   MeSH
• krmivo pro zvířata toxicita   MeSH
• mykotoxiny * MeSH
• terpeny MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Beauverolides (beauveriolides) are abundant, biologically active cyclodepsipeptides produced by many entomopathogenic fungi, including those that are used as biopesticides. Beauverolides act as cholesterol acyltransferase inhibitors in humans; thus, their mode of action has been the subject of pharmacological and clinical research. The cost-effective analytical methods are needed for fast, routine laboratory analysis of beauverolides. We isolated beauverolides from the fungal strain Isaria fumosorosea PFR 97-Apopka and opened the rings of the isolated beauverolides using a pyridine alkaline medium. We separated fractions of cyclic and linearized beauverolides by thin-layer chromatography, and found the chloroform-acetate (9:1, v/v) and chloroform-acetonitrile-acetate (8:1:1, v/v/v) mobile phases, respectively, to be the most efficient. We examined all the fractions by liquid chromatography-mass spectrometry using ion trap and Orbitrap high resolution mass spectrometry. For rapid screening of the contents of cyclic, and, particularly, linearized beauverolides, we developed a novel analytical method that consisted of using capillary electrophoresis coupled with contactless conductivity detection. Furthermore, we improved the separation of the peptides by applying capillary micellar electrokinetic chromatography with the N-cyclohexyl-2-aminoethanesulfonic acid:SDS:NaOH buffer, pH 9.8 as the background electrolyte. The described novel methods allow fast and cost-effective separation of chemically related groups of beauverolides.

• MeSH
• anticholesteremika chemie   izolace a purifikace   MeSH
• chromatografie kapalinová MeSH
• Cordyceps chemie   MeSH
• depsipeptidy chemie   izolace a purifikace   MeSH
• hmotnostní spektrometrie MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

This study examined the effect of two natural toxins (a venom from the parasitic wasp Habrobracon hebetor and destruxin A from the entomopathogenic fungus Metarhizium anisopliae), and one pathogen (the entomopathogenic fungus Isaria fumosorosea) on the activity of basic digestive enzymes in the midgut of the cockroach Periplaneta americana. Simultaneously, the role of adipokinetic hormones (AKH) in the digestive processes was evaluated. The results showed that all tested toxins/pathogens elicited stress responses when applied into the cockroach body, as documented by an increase of AKH level in the central nervous system. The venom from H. hebetor showed no effect on digestive enzyme activities in the ceca and midgut in vitro. In addition, infection by I. fumosorosea caused a decrease in activity of all enzymes in the midgut and a variable decrease in activity in the ceca; application of AKHs did not reverse the inhibition. Destruxin A inhibited the activity of all enzymes in the midgut but none in the ceca in vitro; application of AKHs did reverse this inhibition, and no differences between both cockroach AKHs were found. Overall, the results demonstrated the variable effect of the tested toxins/pathogens on the digestive processes of cockroaches as well as the variable ability of AKH to counteract these effects.

• MeSH
• aktivace enzymů MeSH
• depsipeptidy toxicita   MeSH
• gastrointestinální trakt enzymologie   MeSH
• hmyzí hormony farmakologie   MeSH
• kyselina pyrrolidonkarboxylová analogy a deriváty   farmakologie   MeSH
• oligopeptidy farmakologie   MeSH
• Periplaneta účinky léků   enzymologie   MeSH
• vosí jedy toxicita   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Beauvericin (BEA) is a cyclic hexadepsipeptide, which derives from Cordyceps cicadae. It is also produced by Fusarium species, which are parasitic to maize, wheat, rice and other important commodities. BEA increases ion permeability in biological membranes by forming a complex with essential cations, which may affect ionic homeostasis. Its ion-complexing capability allows BEA to transport alkaline earth metal and alkali metal ions across cell membranes. Importantly, increasing lines of evidence show that BEA has an anticancer effect and can be potentially used in cancer therapeutics. Normally, BEA performs the anticancer effect due to the induced cancer cell apoptosis via a reactive oxygen species-dependent pathway. Moreover, BEA increases the intracellular Ca2+ levels and subsequently regulates the activity of a series of signalling pathways including MAPK, JAK/STAT, and NF-κB, and finally causes cancer cell apoptosis. In vivo studies further show that BEA reduces tumour volumes and weights. BEA especially targets differentiated and invasive cancer types. Currently, the anticancer activity of BEA is a hot topic; however, there is no review article to discuss the anticancer activity of BEA. Therefore, in this review, we have mainly summarized the anticancer activity of BEA and thoroughly discussed its underlying mechanisms. In addition, the human exposure risk assessment of BEA is also discussed. We hope that this review will provide further information for understanding the anticancer mechanisms of BEA.

• MeSH
• depsipeptidy farmakologie   toxicita   MeSH
• Fusarium chemie   MeSH
• hodnocení rizik MeSH
• lidé MeSH
• mykotoxiny farmakologie   toxicita   MeSH
• protinádorové látky farmakologie   toxicita   MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Since apicomplexans represent exclusively parasitic unicellular organisms with medical and economic impacts, the principles of their motility have been studied intensively. By contrast, the movement in apicomplexan basal groups, such as gregarines, remains to be elucidated. The present study focuses on Gregarina garnhami parasitising the digestive tract of the locust Schistocerca gregaria, and investigates the involvement of cytoskeletal elements (the ectoplasmic network and myonemes) and the secretion of mucosubstances during eugregarine gliding motility. Combined microscopic analyses were used to verify the role of actin filaments and membranes' organisation in G. garnhami motility. A freeze-etching analysis of membranes revealed the size, density, and arrangement of intramembranous particles along with the distribution and size of pores and ducts. Experimental assays using actin-modifying drugs (jasplakinolide, cytochalasin D) confirmed that actin most likely plays a role in cell motility, principally in its filamentous form (=F-actin). Myonemes, localised in the border between the ectoplasm and endoplasm, correspond to the concentric bundles of F-actin. Microscopic analyses confirmed that changes in gamonts motility corresponding to the changes in the organisation and density of myonemes and the ectoplasmic network in drug-treated cells, suggesting that these structures might serve as contractile elements facilitating gliding motility in G. garnhami.

• MeSH
• aktiny metabolismus   MeSH
• Apicomplexa účinky léků   MeSH
• cytochalasin D farmakologie   MeSH
• depsipeptidy farmakologie   MeSH
• inhibitory syntézy nukleových kyselin farmakologie   MeSH
• insekticidy farmakologie   MeSH
• pohyb účinky léků   MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• alanin analogy a deriváty   MeSH
• aminokyseliny chemie   izolace a purifikace   MeSH
• anserin analogy a deriváty   MeSH
• biochemické jevy účinky léků   MeSH
• cyklické peptidy MeSH
• depsipeptidy MeSH
• houby izolace a purifikace   metabolismus   MeSH
• karnosin analogy a deriváty   MeSH
• leucin analogy a deriváty   MeSH
• rostliny MeSH
• savci MeSH
• sinice izolace a purifikace   metabolismus   MeSH

Fusarium toxins, Alternaria toxins, and ergot alkaloids represent common groups of mycotoxins that can be found in cereals grown under temperate climatic conditions. Because most of them are chemically and thermally stable, these toxic fungal secondary metabolites might be transferred from grains into the final products. To get information on the commensurate contamination of various cereal-based products collected from the Czech retail market in 2010, the occurrence of "traditional" mycotoxins such as groups of A and B trichothecenes and zearalenone, less routinely determined Alternaria toxins (alternariol, alternariol monomethyl ether and altenuene), ergot alkaloids (ergosine, ergocryptine, ergocristine, and ergocornine) and "emerging" mycotoxins (enniatins A, A1, B, and B1 and beauvericin) were monitored. In a total 116 samples derived from white flour and mixed flour, breakfast cereals, snacks, and flour, only trichothecenes A and B and enniatins were found. Deoxynivalenol was detected in 75% of samples with concentrations ranging from 13 to 594 μg/kg, but its masked form, deoxynivalenol-3-β-d-glucoside, has an even higher incidence of 80% of samples, and concentrations ranging between 5 and 72 μg/kg were detected. Nivalenol was found only in three samples at levels of 30 μg/kg. For enniatins, all of the samples investigated were contaminated with at least one of four target enniatins. Enniatin A was detected in 97% of samples (concentration range of 20-2532 μg/kg) followed by enniatin B with an incidence in 91% of the samples (concentration range of 13-941 μg/kg) and enniatin B1 with an incidence of 80% in the samples tested (concentration range of 8-785 μg/kg). Enniatin A1 was found only in 44% of samples at levels ranging between 8 and 851 μg/kg.

• MeSH
• depsipeptidy analýza   MeSH
• glukosidy analýza   MeSH
• hmotnostní spektrometrie MeSH
• jedlá semena chemie   MeSH
• kontaminace potravin analýza   MeSH
• mouka analýza   MeSH
• mykotoxiny analýza   MeSH
• trichotheceny analýza   MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Beauverolides represent a group of fungal cyclotetradepsipeptides, with only recently recognized potential for human medicine. Reflecting recent preclinical data, this project focuses at the use of beauverolides in modulation of pathologies associated with human metabolic syndrome and with immune system dysregulation. Current massive application of beauverolides in agriculture and forestry raises also the question on potential adverse effects of these applications on the humans, which were never addressed in detail. Thus, we would like to also focus on the association of current use of beauverolides with adverse effects on humans. Beauverolides will be produced under a spectrum of diverse cultivation conditions, which will result in a diversification of their chemical composition. Obtained fungal products will be purified and biochemically characterized in detail, and tested using the battery of biological tests, including those involving human cell lines primary cell isolates. Besides that, the exact mechanisms of metabolisation of beauverolides will be addressed as well.

Reflektujíc nedávný objev potenciálního využití beauverolidů (cyklotetradepsipeptidů produkovaných entomopatogenními houbami) v lékařství, předkládaný projekt navrhuje výzkum beauverolidů z pohledu jejich využitelnosti pro ovlivnění patologických stavů spojených s metabolickým syndromem a s deregulací buněk imunitního systému. Dopady stávající masivní aplikace beauverolidů v zemědělství a lesnictví na člověka dosud nebyly studovány. Zároveň bychom tedy v rámci předkládaného projektu rádi zjistili, zda stávající způsoby využití beauverolidů nejsou spojeny s nežádoucími účinky na člověka. Prostřednictvím modifikací v kultivačních podmínkách zdrojových organismů předpokládáme produkci širokého spektra beauverolidů navzájem odlišného chemického složení, které budou přečištěny, podrobně biochemicky charakterizovány, a následně testovány pomocí baterie biologických testů na lidských buněčných liniích a primárních buněčných izolátech. Zkoumán bude i způsob metabolizace beauverolidů.

• MeSH
• Beauveria izolace a purifikace   MeSH
• depsipeptidy MeSH
• imunitní systém mikrobiologie   patologie   MeSH
• kultivované buňky mikrobiologie   MeSH
• lidé MeSH
• metabolický syndrom mikrobiologie   patologie   MeSH
• Check Tag
• lidé MeSH

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• mikrobiologie, lékařská mikrobiologie
• botanika
• NLK Publikační typ
• závěrečné zprávy o řešení grantu AZV MZ ČR

Mycotoxin contamination of dietary supplements represents a possible risk for human health, especially in the case of products intended for people suffering from certain health conditions. The aim of this study was to assess the extent of this problem based on analyses of a wide set of herbal-based dietary supplements intended for various purposes: (i) treatment of liver diseases (milk thistle); (ii) reduction of menopause effects (red clover, flax seed, and soy); and (iii) preparations for general health support (green barley, nettle, goji berries, yucca, etc.) The analytical method including 57 mycotoxins was based on a QuEChERS-like (quick, easy, cheap, effective, rugged, safe) approach and ultrahigh performance liquid chromatography coupled with tandem mass spectrometry. The main mycotoxins determined were Fusarium trichothecenes, zearalenone and enniatins, and Alternaria mycotoxins. Co-occurrence of enniatins, HT-2/T-2 toxins, and Alternaria toxins was observed in many cases. The highest mycotoxin concentrations were found in milk thistle-based supplements (up to 37 mg/kg in the sum).

• MeSH
• depsipeptidy analýza   MeSH
• kontaminace potravin analýza   MeSH
• lidé MeSH
• mykotoxiny analýza   MeSH
• potravní doplňky analýza   MeSH
• rizikové faktory MeSH
• rostlinné přípravky chemie   MeSH
• tandemová hmotnostní spektrometrie metody   MeSH
• trichotheceny analýza   MeSH
• vysokoúčinná kapalinová chromatografie metody   MeSH
• zearalenon analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH