Ferricyanide reductase of rose plasma membranes is regulated by nitrogen supply

Summary The ability of suspension-cultured rose (Rosa damascena Mill. cv Gloire de Guilan) cells to reduce ferricyanide is decreased by 50% during an overnight incubation in a low-nutrient (1 mM CaCl₂, 0.1 mM KCl) solution. This loss is not observed when nitrate and/or glutamate is added to the low-nutrient medium, but it occurs in medium containing all the components needed for normal growth except nitrate plus glutamate. Thus, the cells possess both constitutive and inducible enzymes for the reduction of ferricyanide, and nitrate or glutamate is both necessary and sufficient to stimulate the production of the inducible enzyme.     

The action of excessive,inorganic silicon (Si) on the mineral metabolism of calcium (Ca) and magnesium (Mg)

The influence of silicon treatment on the levels of calcium and magnesium in blood serum and tissues was studied in rats. The concentrations of both elements were estimated in samples of sera and tissues of rats receiving per os a soluble, inorganic silicon compound—sodium metasilicate nonahydrate (Na₂SiO₃·9H₂O (REACHIM, USSR)), dissolved in the animals' drinking water. A decrease of magnesium concentration in serum was observed with accompanying elevation of registered calcemia. Moreover, a reduction of tissue calcium levels was found with a simultaneous increase of magnesium tissue pool. The results provide evidence for silicon involvement in mineral metabolism. It could result in a modification of pathological processes concerning bone tissue.     

Concurrent quantitative HPLC–mass spectrometry profiling of small selenium species in human serum and urine after ingestion of selenium supplements

Selenium metabolic patterns in the human body originating from five distinct selenium dietary sources, selenate, selenite, selenomethionine (SeMet), methylselenocysteine (MeSeCys) and selenized yeast, were investigated by performing concurrent HPLC–mass spectrometric analysis of human serum and urine. Total selenium and selenium species time profiles were generated by sampling and analyzing serum and urine from volunteers treated with selenium supplements, up to 5 and 24 h following ingestion, respectively. We found that an increase in total serum selenium levels, accompanied by elevated selenium urinary excretion, was the common pattern for all treatments, except for that of selenite supplementation. Selenosugar 1 was a universal serum metabolite in all treatments, indicating that ingested selenium is favorably metabolized to the sugar. Except for selenite and selenized yeast ingestion, these patterns were reflected in the urine time series of the different treatments. Selenosugar 1 was the major selenium species present in urine in all treatments except for the selenate treatment, accounting for about 80% of the identified excreted species within 24 h of ingestion. Furthermore, the urinary metabolite trimethylselenonium ion (TMSe) was detected for the first time in human background serum by using HPLC coupled to elemental and molecular mass spectrometry. The concurrent monitoring of non-protein selenium species in both body fluids provides the relation between bioavailability and excretion of the individual ingested species and of their metabolic products, while the combined use of elemental and molecular mass spectrometry enables the accurate quantitation of structurally confirmed species. This successfully applied approach is anticipated to be a useful tool for more extensive future studies into human selenium metabolism.     

Identification and in silico prediction of metabolites of tebufenozide derivatives by major human cytochrome P450 isoforms

Cytochrome P450 (CYP) enzymes constitute a superfamily of heme-containing monooxygenases. CYPs are involved in the metabolism of many chemicals such as drugs and agrochemicals. Therefore, examining the metabolic reactions by each CYP isoform is important to elucidate their substrate recognition mechanisms. The clarification of these mechanisms may be useful not only for the development of new drugs and agrochemicals, but also for risk assessment of chemicals. In our previous study, we identified the metabolites of tebufenozide, an insect growth regulator, formed by two human CYP isoforms: CYP3A4 and CYP2C19. The accessibility of each site of tebufenozide to the reaction center of CYP enzymes and the susceptibility of each hydrogen atom for metabolism by CYP enzymes were evaluated by a docking simulation and hydrogen atom abstraction energy estimation at the density functional theory level, respectively. In this study, the same in silico prediction method was applied to the metabolites of tebufenozide derivatives by major human CYPs (CYP1A2, 2C9, 2C19, 2D6, and 3A4). In addition, the production rate of the metabolites by CYP3A4 was quantitively analyzed by frequency based on docking simulation and hydrogen atom abstraction energy using the classical QSAR approach. Then, the obtained QSAR model was applied to predict the sites of metabolism and the metabolite production order by each CYP isoform.     

AMPK,a Regulator of Metabolism and Autophagy,Is Activated by Lysosomal Damage via a Novel Galectin-Directed Ubiquitin Signal Transduction System

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Relationship between fern development and CAM in Pyrrosia piloselloides (L.) Price

Pyrrosia piloselloides (L.) Price is a constitutive CAM plant in the sporophytic phase of its life-cycle. Newly developed sporophytes, still attached to the gametophytes, showed signs of CAM expression in terms of diurnal changes in titratable acidity of the tissues. The gametophytes did not exhibit CAM. This revised version was published online in June 2006 with corrections to the Cover Date.     

The SGLT2 inhibitor dapagliflozin promotes systemic FFA mobilization,enhances hepatic β-oxidation,and induces ketosis

Sodium-glucose cotransporter 2 (SGLT2) inhibitors have been shown to increase ketone bodies in patients with type 2 diabetes; however, the underlying mechanisms have not been fully elucidated. Here we examined the effect of the SGLT2 inhibitor dapagliflozin (1 mg/kg/day, formulated in a water, PEG400, ethanol, propylene glycol solution, 4 weeks) on lipid metabolism in obese Zucker rats. Fasting FFA metabolism was assessed in the anesthetized state using a [9,10-³H(N)]-palmitic acid tracer by estimating rates of plasma FFA appearance (R_a), whole-body FFA oxidation (R_ox), and nonoxidative disposal (R_st). In the liver, clearance (K_β-ox) and flux (R_β-ox) of FFA into β-oxidation were estimated using [9,10-³H]-(R)-bromopalmitate/[U-¹⁴C]palmitate tracers. As expected, dapagliflozin induced glycosuria and a robust antidiabetic effect; treatment reduced fasting plasma glucose and insulin, lowered glycated hemoglobin, and increased pancreatic insulin content compared with vehicle controls. Dapagliflozin also increased plasma FFA, R_a, R_ox, and R_st with enhanced channeling toward oxidation versus storage. In the liver, there was also enhanced channeling of FFA to β-oxidation, with increased K_β-ox, R_β-ox and tissue acetyl-CoA, compared with controls. Finally, dapagliflozin increased hepatic HMG-CoA and plasma β-hydroxybutyrate, consistent with a specific enhancement of ketogenesis. Since ketogenesis has not been directly measured, we cannot exclude an additional contribution of impaired ketone body clearance to the ketosis. In conclusion, this study provides evidence that the dapagliflozin-induced increase in plasma ketone bodies is driven by the combined action of FFA mobilization from adipose tissue and diversion of hepatic FFA toward β-oxidation.     

Inhibition of Mitochondrial Complex II by the Anticancer Agent Lonidamine

The antitumor agent lonidamine (LND; 1-(2,4-dichlorobenzyl)-1H-indazole-3-carboxylic acid) is known to interfere with energy-yielding processes in cancer cells. However, the effect of LND on central energy metabolism has never been fully characterized. In this study, we report that a significant amount of succinate is accumulated in LND-treated cells. LND inhibits the formation of fumarate and malate and suppresses succinate-induced respiration of isolated mitochondria. Utilizing biochemical assays, we determined that LND inhibits the succinate-ubiquinone reductase activity of respiratory complex II without fully blocking succinate dehydrogenase activity. LND also induces cellular reactive oxygen species through complex II, which reduced the viability of the DB-1 melanoma cell line. The ability of LND to promote cell death was potentiated by its suppression of the pentose phosphate pathway, which resulted in inhibition of NADPH and glutathione generation. Using stable isotope tracers in combination with isotopologue analysis, we showed that LND increased glutaminolysis but decreased reductive carboxylation of glutamine-derived α-ketoglutarate. Our findings on the previously uncharacterized effects of LND may provide potential combinational therapeutic approaches for targeting cancer metabolism.