In natural environments, photosynthetic organisms adjust their metabolism to cope with the fluctuating availability of combined nitrogen sources, a growth-limiting factor. For acclimation, the dynamic degradation/synthesis of tetrapyrrolic pigments, as well as of the amino acid arginine, is pivotal; however, there has been no evidence that these processes could be functionally coupled. Using co-immunopurification and spectral shift assays, we found that in the cyanobacterium Synechocystis sp. PCC 6803, the arginine metabolism-related ArgD and CphB enzymes form protein complexes with Gun4, an essential protein for chlorophyll biosynthesis. Gun4 binds ArgD with high affinity, and the Gun4-ArgD complex accumulates in cells supplemented with ornithine, a key intermediate of the arginine pathway. Elevated ornithine levels restricted de novo synthesis of tetrapyrroles, which arrested the recovery from nitrogen deficiency. Our data reveal a direct crosstalk between tetrapyrrole biosynthesis and arginine metabolism that highlights the importance of balancing photosynthetic pigment synthesis with nitrogen homeostasis.

• Klíčová slova
• CP: Plants, Synechocystis, arginine metabolism, bilins, chlorophyll, genome-uncoupled-4, nitrogen homeostasis, tetrapyrrole biosynthesis,
• MeSH
• arginin metabolismus   MeSH
• chlorofyl metabolismus   MeSH
• dusík MeSH
• ornithin MeSH
• Synechocystis * metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• arginin MeSH
• chlorofyl MeSH
• dusík MeSH
• ornithin MeSH

Both Mycoplasma hominis and Trichomonas vaginalis utilize arginine as an energy source via the arginine dihydrolase (ADH) pathway. It has been previously demonstrated that M. hominis forms a stable intracellular relationship with T. vaginalis; hence, in this study we examined the interaction of two localized ADH pathways by comparing T. vaginalis strain SS22 with the laboratory-generated T. vaginalis strain SS22-MOZ2 infected with M. hominis MOZ2. The presence of M. hominis resulted in an approximately 16-fold increase in intracellular ornithine and a threefold increase in putrescine, compared with control T. vaginalis cultures. No change in the activity of enzymes of the ADH pathway could be demonstrated in SS22-MOZ2 compared with the parent SS22, and the increased production of ornithine could be attributed to the presence of M. hominis. Using metabolic flow analysis it was determined that the elasticity of enzymes of the ADH pathway in SS22-MOZ2 was unchanged compared with the parent SS22; however, the elasticity of ornithine decarboxylase (ODC) in SS22 was small, and it was doubled in SS22-MOZ2 cells. The potential benefit of this relationship to both T. vaginalis and M. hominis is discussed.

• MeSH
• arginin metabolismus   MeSH
• hydrolasy chemie   genetika   metabolismus   MeSH
• molekulární sekvence - údaje MeSH
• Mycoplasma hominis metabolismus   MeSH
• ornithindekarboxylasa chemie   genetika   metabolismus   MeSH
• protozoální proteiny chemie   genetika   metabolismus   MeSH
• sekvence aminokyselin MeSH
• sekvenční seřazení MeSH
• Trichomonas vaginalis enzymologie   genetika   metabolismus   mikrobiologie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• arginin MeSH
• arginine deiminase MeSH Prohlížeč
• hydrolasy MeSH
• ornithindekarboxylasa MeSH
• protozoální proteiny MeSH

BACKGROUND: Multiple prokaryotic lineages use the arginine deiminase (ADI) pathway for anaerobic energy production by arginine degradation. The distribution of this pathway among eukaryotes has been thought to be very limited, with only two specialized groups living in low oxygen environments (Parabasalia and Diplomonadida) known to possess the complete set of all three enzymes. We have performed an extensive survey of available sequence data in order to map the distribution of these enzymes among eukaryotes and to reconstruct their phylogenies. RESULTS: We have found genes for the complete pathway in almost all examined representatives of Metamonada, the anaerobic protist group that includes parabasalids and diplomonads. Phylogenetic analyses indicate the presence of the complete pathway in the last common ancestor of metamonads and heterologous transformation experiments suggest its cytosolic localization in the metamonad ancestor. Outside Metamonada, the complete pathway occurs rarely, nevertheless, it was found in representatives of most major eukaryotic clades. CONCLUSIONS: Phylogenetic relationships of complete pathways are consistent with the presence of the Archaea-derived ADI pathway in the last common ancestor of all eukaryotes, although other evolutionary scenarios remain possible. The presence of the incomplete set of enzymes is relatively common among eukaryotes and it may be related to the fact that these enzymes are involved in other cellular processes, such as the ornithine-urea cycle. Single protein phylogenies suggest that the evolutionary history of all three enzymes has been shaped by frequent gene losses and horizontal transfers, which may sometimes be connected with their diverse roles in cellular metabolism.

• Klíčová slova
• Arginine deiminase, Carbamate kinase, Metamonada, Ornithine transcarbamylase, Phylogeny, Preaxostyla, Protists,
• MeSH
• Archaea metabolismus   MeSH
• arginin metabolismus   MeSH
• Diplomonadida enzymologie   MeSH
• Eukaryota klasifikace   genetika   metabolismus   MeSH
• fylogeneze MeSH
• hydrolasy metabolismus   MeSH
• metabolické sítě a dráhy * MeSH
• molekulární evoluce * MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• arginin MeSH
• arginine deiminase MeSH Prohlížeč
• hydrolasy MeSH

Metabolic rewiring is a characteristic hallmark of cancer cells. This phenomenon sustains uncontrolled proliferation and resistance to apoptosis by increasing nutrients and energy supply. However, reprogramming comes together with vulnerabilities that can be used against tumor and can be applied in targeted therapy. In the last years, the genetic background of tumors has been identified thoroughly and new therapies targeting those mutations tested. Nevertheless, we propose that targeting the phenotype of cancer cells could be another way of treatment aiming to avoid drug resistance and non-responsiveness of cancer patients. Amino acid metabolism is part of the altered processes in cancer cells. Amino acids are building blocks and also sensors of signaling pathways regulating main biological processes. In this comprehensive review, we described four amino acids (asparagine, arginine, methionine, and cysteine) which have been actively investigated as potential targets for anti-tumor therapy. Asparagine depletion is successfully used for decades in the treatment of acute lymphoblastic leukemia and there is a strong implication to apply it to other types of tumors. Arginine auxotrophic tumors are great candidates for arginine-starvation therapy. Higher requirement for essential amino acids such as methionine and cysteine point out promising targetable weaknesses of cancer cells.

• Klíčová slova
• Amino acid metabolism, Arginine, Asparagine, Cancer, Cysteine, Methionine, Targeted therapy,
• MeSH
• aminokyseliny metabolismus   MeSH
• arginin metabolismus   terapeutické užití   MeSH
• asparagin * metabolismus   terapeutické užití   MeSH
• cystein metabolismus   MeSH
• lidé MeSH
• methionin MeSH
• nádory * metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• aminokyseliny MeSH
• arginin MeSH
• asparagin * MeSH
• cystein MeSH
• methionin MeSH

Arginine repressor of E. coli is a multifunctional hexameric protein that provides feedback regulation of arginine metabolism upon activation by the negatively cooperative binding of L-arginine. Interpretation of this complex system requires an understanding of the protein's conformational landscape. The ~50 kDa hexameric C-terminal domain was studied by 100 ns molecular dynamics simulations in the presence and absence of the six L-arg ligands that bind at the trimer-trimer interface. A rotational shift between trimers followed by rotational oscillation occurs in the production phase of the simulations only when L-arg is absent. Analysis of the system reveals that the degree of rotation is correlated with the number of hydrogen bonds across the trimer interface. The trajectory presents frames with one or more apparently open binding sites into which one L-arg could be docked successfully in three different instances, indicating that a binding-competent state of the system is occasionally sampled. Simulations of the resulting singly-liganded systems reveal for the first time that the binding of one L-arg results in a holoprotein-like conformational distribution.

• MeSH
• apoproteiny chemie   metabolismus   MeSH
• arginin chemie   metabolismus   MeSH
• konformace proteinů MeSH
• ligandy MeSH
• proteiny z Escherichia coli chemie   metabolismus   MeSH
• represorové proteiny chemie   metabolismus   MeSH
• simulace molekulární dynamiky MeSH
• simulace molekulového dockingu MeSH
• vazba proteinů MeSH
• vazebná místa MeSH
• vodíková vazba MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH
• Názvy látek
• apoproteiny MeSH
• arginin MeSH
• ArgR protein, E coli MeSH Prohlížeč
• ligandy MeSH
• proteiny z Escherichia coli MeSH
• represorové proteiny MeSH

Although dendritic cells (DCs) control the priming of the adaptive immunity response, a comprehensive description of their behavior at the protein level is missing. The introduction of the quantitative proteomic technique of metabolic labeling (SILAC) into the field of DC research would therefore be highly beneficial. To achieve this, we applied SILAC labeling to primary bone marow-derived DCs (BMDCs). These cells combine both biological relevance and experimental feasibility, as their in vitro generation permits the use of (13)C/(15)N-labeled amino acids. Interestingly, BMDCs appear to exhibit a very active arginine metabolism. Using standard cultivation conditions, ∼20% of all protein-incorporated proline was a byproduct of heavy arginine degradation. In addition, the dissipation of (15)N from labeled arginine to the whole proteome was observed. The latter decreased the mass accuracy in MS and affected the natural isotopic distribution of peptides. SILAC-connected metabolic issues were shown to be enhanced by GM-CSF, which is used for the differentiation of DC progenitors. Modifications of the cultivation procedure suppressed the arginine-related effects, yielding cells with a proteome labeling efficiency of ≥90%. Importantly, BMDCs generated according to the new cultivation protocol preserved their resemblance to inflammatory DCs in vivo, as evidenced by their response to LPS treatment.

• MeSH
• arginin metabolismus   MeSH
• buňky kostní dřeně metabolismus   MeSH
• dendritické buňky metabolismus   MeSH
• faktor stimulující granulocyto-makrofágové kolonie metabolismus   MeSH
• kultivované buňky MeSH
• molekulární sekvence - údaje MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• prolin metabolismus   MeSH
• proteom * MeSH
• sekvence aminokyselin MeSH
• tandemová hmotnostní spektrometrie MeSH
• vysokoúčinná kapalinová chromatografie MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• arginin MeSH
• faktor stimulující granulocyto-makrofágové kolonie MeSH
• prolin MeSH
• proteom * MeSH

In ergosterol-containing energized yeast plasma membrane vesicles nystatin (5-10 micrograms/mg total lipid) caused a massive efflux of pre-accumulated arginine while the membrane potential (the principal driving force; -110 mV) decreased by only 10-30 mV. Neither the substrate fluxes nor the membrane potential was influenced by nystatin when the permease was reconstituted in ergosterol-free phospholipid vesicles. The same effect of nystatin was found with the reconstituted sugar transporter from Chlorella kessleri. It is suggested that nystatin binding to ergosterol in the vicinity of the permease releases the transport protein from its coupling to energy and converts it to a facilitator.

• MeSH
• arginin metabolismus   MeSH
• biologický transport MeSH
• buněčná membrána metabolismus   MeSH
• membránové potenciály MeSH
• metabolismus sacharidů * MeSH
• nystatin farmakologie   MeSH
• Saccharomyces cerevisiae metabolismus   MeSH
• transportní proteiny metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• arginin MeSH
• nystatin MeSH
• transportní proteiny MeSH

We investigated the effects of in vivo treatment with the angiotensin-converting enzyme inhibitor (ACE-I) captopril and/or of in vitro administration of L-arginine on the metabolism and ischemia-reperfusion injury of the isolated perfused rat myocardium. Captopril (50 mg/l in drinking water, 4 weeks) raised the myocardial content of glycogen. After 25-min global ischemia, captopril treatment, compared with the controls, resulted in lower rates of lactate dehydrogenase release during reperfusion (8.58 +/- 1.12 vs. 13.39 +/- 1.88 U/heart/30 min, p<0.05), lower myocardial lactate contents (11.34 +/- 0.93 vs. 21.22 +/- 4.28 micromol/g d.w., p<0.05) and higher coronary flow recovery (by 25%), and prevented the decrease of NO release into the perfusate during reperfusion. In control hearts L-arginine added to the perfusate (1 mmol/l) 10 min before ischemia had no effect on the parameters evaluated under our experimental conditions, presumably because of sufficient saturation of the myocardium with L-arginine. In the hearts of captopril-treated rats, L-arginine further increased NO production during reperfusion and the cGMP content before ischemia. Our results have shown that long-term captopril treatment increases the energy potential and has a beneficial effect on tolerance of the isolated heart to ischemia. L-arginine added into the perfusate potentiates the effect of captopril on the NO signaling pathway.

• MeSH
• arginin farmakologie   MeSH
• guanosinmonofosfát cyklický metabolismus   MeSH
• inhibitory ACE farmakologie   MeSH
• kaptopril farmakologie   MeSH
• krysa rodu Rattus MeSH
• myokard metabolismus   MeSH
• oxid dusnatý metabolismus   MeSH
• potkani Wistar MeSH
• reperfuzní poškození myokardu farmakoterapie   metabolismus   MeSH
• synergismus léků MeSH
• techniky in vitro MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• arginin MeSH
• guanosinmonofosfát cyklický MeSH
• inhibitory ACE MeSH
• kaptopril MeSH
• oxid dusnatý MeSH

The reversibility of arginine accumulation was followed in exponentially growing cells of Saccharomyces cerevisiae and in the same cells transferred to non-growing energized conditions. Under non-growing conditions the accumulated arginine is retained in the cells while in exponentially growing cells the accumulated radioactivity is released after the addition of high external concentrations of arginine. There are indications that the process is saturable. The accumulated arginine is not exchanged for other related amino acids (L-citrulline, L-histidine). Only L-lysine (a low-affinity substrate of the specific arginine permease) provokes partial radioactivity efflux from the cells. The switch of the arginine-related radioactive label efflux to its complete retention in the cells after changing the growth conditions occurs within a few minutes and is tentatively attributed to two concomitantly occurring events: (1) the actual presence of radioactive arginine (not its metabolite(s)) in the cell and (2) a modification of the specific arginine permease. The specific exchange of arginine described in the present study contrasts with the currently widely accepted opinion of unidirectionality of amino acid fluxes in yeast. The reasons why this phenomenon has not been observed before are discussed.

• MeSH
• arginin metabolismus   MeSH
• biologický transport MeSH
• citrulin metabolismus   MeSH
• fungální proteiny * MeSH
• geny hub MeSH
• lysin metabolismus   MeSH
• membránové transportní proteiny genetika   MeSH
• Saccharomyces cerevisiae genetika   růst a vývoj   metabolismus   MeSH
• transportní systémy aminokyselin * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• arginin MeSH
• CAN1 protein, Candida albicans MeSH Prohlížeč
• citrulin MeSH
• fungální proteiny * MeSH
• lysin MeSH
• membránové transportní proteiny MeSH
• transportní systémy aminokyselin * MeSH

BACKGROUND AND AIM: Patients with methylmalonic acidemia (MMA) and propionic acidemia (PA) and urea cycle disorders (UCD), treated with a protein restricted diet, are prone to growth failure. To obtain optimal growth and thereby efficacious protein incorporation, a diet containing the essential and functional amino acids for growth is necessary. Optimal growth will result in improved protein tolerance and possibly a decrease in the number of decompensations. It thus needs to be determined if amino acid deficiencies are associated with the growth retardation in these patient groups. We studied the correlations between plasma L-arginine levels, plasma branched chain amino acids (BCAA: L-isoleucine, L-leucine and L-valine) levels (amino acids known to influence growth), and height in MMA/PA and UCD patients. METHODS: We analyzed data from longitudinal visits made in stable metabolic periods by patients registered at the European Registry and Network for Intoxication Type Metabolic Diseases (E-IMD, Chafea no. 2010 12 01). RESULTS: In total, 263 MMA/PA and 311 UCD patients were included, all aged below 18 years of age. In patients with MMA and PA, height z-score was positively associated with patients' natural-protein-to-energy prescription ratio and their plasma L-valine and L-arginine levels, while negatively associated with the amount of synthetic protein prescription and their age at visit. In all UCDs combined, height z-score was positively associated with the natural-protein-to-energy prescription ratio. In those with carbamylphosphate synthetase 1 deficiency (CPS1-D), those with male ornithine transcarbamylase deficiency (OTC-D), and those in the hyperornithinemia-hyperammonemia-homocitrullinuria (HHH) syndrome subgroup, height z-score was positively associated with patients' plasma L-leucine levels. In those with argininosuccinate synthetase deficiency (ASS-D) and argininosuccinate lyase deficiency (ASL-D), height was positively associated with patients' plasma L-valine levels. CONCLUSION: Plasma L-arginine and L-valine levels in MMA/PA patients and plasma L-leucine and L-valine levels in UCD patients, as well as the protein-to-energy prescription ratio in both groups were positively associated with height. Optimization of these plasma amino acid levels is essential to support normal growth and increase protein tolerance in these disorders. Consequently this could improve the protein-to-energy intake ratio.

• Klíčová slova
• Body height, Branched-chain amino acids, Dietary and supplemental treatment, L-arginine, Organic acidurias, Urea cycle disorders,
• MeSH
• arginin krev   MeSH
• dieta MeSH
• dítě MeSH
• lidé MeSH
• longitudinální studie MeSH
• mladiství MeSH
• poruchy růstu dietoterapie   etiologie   MeSH
• předškolní dítě MeSH
• propionová acidemie komplikace   MeSH
• registrace MeSH
• tělesná výška MeSH
• větvené aminokyseliny krev   MeSH
• vrozené poruchy cyklu močoviny komplikace   MeSH
• vrozené poruchy metabolismu aminokyselin komplikace   dietoterapie   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• arginin MeSH
• větvené aminokyseliny MeSH