Glutamate Dehydrogenase Activity Research Articles

Water-Nutrient Coupling Strategies That Improve the Carbon, Nitrogen Metabolism, and Yield of Cucumber under Sandy Cultivated Land

The purpose of this study was to explore the carbon and nitrogen metabolism mechanisms of sand-cultivated cucumbers under different deficit irrigation–nitrogen management strategies and provide a theoretical basis for their greenhouse management. This study set up two factors, the deficit irrigation level and the nitrogen application rate, and conducted an experiment on deficit irrigation–nitrogen coupling of sand-cultivated cucumbers using a quadratic saturation D–optimal design. Seven treatments were set up in the experiment, to measure the soluble sugar and protein contents, as well as the activity of key enzymes for carbon and nitrogen metabolism at five different growth stages. The results indicate that the 80% irrigation with 623 kg N hm−2 (IN4) treatment significantly improved the soluble sugar, protein, and actual leaf nitrogen contents of cucumber at the five different growth stages and, as a result, achieved higher sucrose synthase (SS) and sucrose phosphate synthase (SPS) activities in the cucumber leaves. Furthermore, such improvements were due to the reduction in oxidative damage of sand–cultivated cucumber at various growth stages. The IN4 and 89% irrigation with 1250 kg N hm−2 (IN5) treatments significantly increased the activities of RuBisCO, catalase (CAT), peroxidise (POD), and superoxide dismutase (SOD) at various growth stages of sand-cultivated cucumber. The higher activities of glutamate dehydrogenase (GLDH), glutamate synthase (GOGAT), nitrate reductase (NR), glutamine synthase (GS), acid invertase enzyme (AIE), neutral invertase enzyme (NIE), and better antioxidative enzyme activities were recorded under the IN4 treatments at various growth stages, which effectively improve (69.6%) cucumber yield. The soil properties, carbon and nitrogen metabolism, and antioxidant metabolism were positively correlated with sand-cultivated cucumber yield in a greenhouse. We concluded that the IN4 treatment was the better deficit irrigation–nitrogen management strategy because it considerably improves carbon and nitrogen metabolism, antioxidant enzyme activities, and sand–cultivated cucumber yield in a greenhouse.

Dietary protein load affects the energy and nitrogen balance requiring liver glutamate dehydrogenase to maintain physical activity.

Provision of amino acids to the liver is instrumental for gluconeogenesis while it requires safe disposal of the amino group. The mitochondrial enzyme glutamate dehydrogenase (GDH) is central for hepatic ammonia detoxification by deaminating excessive amino acids towards ureagenesis and preventing hyperammonemia. The present study investigated the early adaptive responses to changes in dietary protein intake in control mice and liver-specific GDH knockout mice (Hep-Glud1-/-). Mice were fed chow diets with a wide coverage of protein contents; i.e. suboptimal 10%, standard 20%, over optimal 30%, and high 45% protein diets; switched every 4 days. Metabolic adaptations of the mice were assessed in calorimetric chambers before tissue collection and analyses. Hep-Glud1-/- mice exhibited impaired alanine induced gluconeogenesis and constitutive hyperammonemia. The expression and activity of GDH in liver lysates were not significantly changed by the different diets. However, applying an in situ redox-sensitive assay on cryopreserved tissue sections revealed higher hepatic GDH activity in mice fed the high-protein diets. On the same section series, immunohistochemistry provided corresponding mapping of the GDH expression. Cosinor analysis from calorimetric chambers showed that the circadian rhythm of food intake and energy expenditure was altered in Hep-Glud1-/- mice. In control mice, energy expenditure shifted from carbohydrate to amino acid oxidation when diet was switched to high protein content. This shift was impaired in Hep-Glud1-/- mice and consequently the spontaneous physical activity was markedly reduced in GDH knockout mice. These data highlight the central role of liver GDH in the energy balance adaptation to dietary proteins.

Feeding strategy and feed protein level affect the gut microbiota of common carp (Cyprinus carpio).

Common carp (Cyprinus carpio) were fed food with different protein concentrations following different feeding regimes, which were previously shown to affect growth, nitrogen excretion and amino acid catabolism. 16S rRNA gene amplicon sequencing was performed to investigate the gut microbiota of these fish. Lower dietary protein content increased microbial richness, while the combination of demand feeding and dietary protein content affected the composition of the gut microbiota. Hepatic glutamate dehydrogenase (GDH) activity was correlated to the composition of the gut microbiota in all dietary treatments. We found that demand-fed carp fed a diet containing 39% protein had a significantly higher abundance of Beijerinckiaceae compared to other dietary groups. Network analysis identified this family and two Rhizobiales families as hubs in the microbial association network. In demand-fed carp, the microbial association network had significantly fewer connections than in batch-fed carp. In contrast to the large effects of the feeding regime and protein content of the food on growth and nitrogen metabolism, it had only limited effects on gut microbiota composition. However, correlations between gut microbiota composition and liver GDH activity showed that host physiology and gut microbiota are connected, which warrants functional studies into the role of the gut microbiota in fish physiology.

Alpha-ketoglutarate supplementation in long-lived Drosophila melanogaster: Impact on lifespan and metabolic responses.

Studies on antiaging remedies in insect models sometimes show discrepancies in results. These discrepancies could be explained by different responses of short- and long-lived strains on the antiaging remedies. The purpose of the study was to test whether life-prolonging effects of alpha-ketoglutarate (AKG), observed in nematodes and fruit flies, would be reproduced in long-lived Drosophila melanogaster flies. Lifespan was assayed in flies kept in demographic cages. Fecundity, proportion of flies capable of negative geotaxis, starvation resistance, time of heat coma onset, levels of triacyglycerols, body glucose, glycogen, activities of glutamate dehydrogenase, catalase, glutathione-S-transferase, hexokinase, phosphofructokinase, pyruvate kinase, lactate, and glutamate dehydrogenases were assessed. Dietary AKG did not affect fly lifespan on the diet with 5% yeast and 5% sucrose (5Y:5S) and on the diet with 9% yeast and 1% sucrose (9Y:1S), but increased lifespan on the low-protein diet (1Y:9S). Twenty-five-day-old female flies fed a 5Y:5S diet with 10 mM AKG for 3 weeks, did not differ from the control group (without AKG) in climbing activity, resistance to heat stress, and starvation. The levels of glucose and glycogen were unaffected but the levels of triacylglycerols were lower in AKG-fed female flies. No differences in activities of glycolytic enzymes, NADPH-producing enzymes, glutamate dehydrogenase, oxygen consumption, and levels of oxidative stress markers were observed between the control and AKG-fed flies. However, AKG-fed flies had lower activities of catalase and glutathione-S-transferase. These results suggest that potential antiaging remedies, such as AKG, may not extend lifespan in long-living organisms despite influencing several metabolic parameters.

Expression of hepatic genes involved in bile acid metabolism in dairy cows with fatty liver

Bile acids are cholesterol-derived molecules that are primarily produced in the liver. In nonruminants with fatty liver, overproduction of bile acids is associated with liver injury. During the transition period, fatty liver is a metabolic disorder that can affect up to 50% of high-producing dairy cows. The purpose of this study was to provide a comprehensive evaluation on hepatic bile acid metabolism in dairy cows with fatty liver by assessing expression changes of genes involved in bile acid synthesis, export and uptake. The serum activities of aspartate aminotransferase, alanine aminotransferase and glutamate dehydrogenase and concentration of total bile acids were all greater, whereas serum concentration of total cholesterol was lower in cows with fatty liver than in healthy cows. Content of total bile acids was higher but total cholesterol was slightly lower in liver tissues from fatty liver cows than from healthy cows. The hepatic mRNA abundance of cholesterol 7a-hydroxylase (CYP7A1), hydroxy-delta-5-steroid dehydrogenase, 3 β- and steroid delta-isomerase 7 (HSD3B7) and sterol 12α-hydroxylase (CYP8B1), enzymes involved in the classic pathway of bile acid synthesis, was higher in fatty liver cows than in healthy cows. Compared with healthy cows, the hepatic mRNA abundance of alternative bile acid synthesis pathway-related genes sterol 27-hydroxylase (CYP27A1) and oxysterol 7α-hydroxylase (CYP7B1) did not differ in cows with fatty liver. The protein and mRNA abundance of bile acid transporter bile salt efflux pump (BSEP) were lower in the liver of dairy cow with fatty liver. Compared with healthy cows, the hepatic mRNA abundance of bile acid transporters solute carrier family 51 subunit α (SLC51A), ATP binding cassette subfamily C member 1 (ABCC1) and 3 (ABCC3) was greater in cows with fatty liver, whereas the solute carrier family 51 subunit β (SLC51B) did not differ. The expression of genes involved in bile acid uptake, including solute carrier family 10 member 1 (NTCP), solute carrier organic anion transporter family member 1A2 (SLCO1A2) and 2B1 (SLCO2B1) was upregulated in dairy cows with fatty liver. Furthermore, the hepatic protein and mRNA abundance of bile acid metabolism regulators farnesoid X receptor (FXR) and small heterodimer partner (SHP) were lower in cows with fatty liver than in healthy cows. Overall, these data suggest that inhibition of FXR signaling pathway may lead to the increased bile acid synthesis and uptake and decreased secretion of bile acids from hepatocytes to the bile, which elevates hepatic bile acids content in dairy cows with fatty liver. As the hepatotoxicity of bile acids has been demonstrated on nonruminant hepatocytes, it is likely that the liver injury is induced by increased hepatic bile acids content in dairy cows with fatty liver.

Does jasmonic acid mitigate the adverse effects of salt stress on wheat through the enhancement of ascorbate biosynthesis and the induction of glutamate dehydrogenase activity?

AbstractBackgroundSalt stress is one of the most common abiotic stresses, reducing plant growth and productivity. Thus, the development of suitable management practices to minimize the deleterious effects of salt stress has become necessary.AimsThis study was conducted to investigate the possible mechanisms underlying salt tolerance conferred by jasmonic acid (JA).MethodsSalt‐stressed wheat seedlings were supplemented with 1 mM JA and/or 1 mM ibuprofen (IBU), an inhibitor of endogenous JA biosynthesis, in the culture medium.ResultsThe obtained results showed that salt stress significantly decreased shoot and root dry weight production and relative water contents. This was associated with a noteworthy reduction in leaf and root ascorbate (AsA) concentrations, as well as glutamine synthetase (GS), glutamate synthase (GOGAT), and glutamate dehydrogenase (GDH) activities. Exogenously supplied JA did not affect GS and GOGAT activities in leaves and roots of salt‐treated seedlings. However, noticeable enhancements were observed in growth, AsA concentrations, as well as GDH activities. Likewise, the inhibition of JA biosynthesis by IBU application was accompanied by a significant decrease in seedlings’ growth associated with a noticeable reduction in AsA concentrations and GDH activities. The decreases in growth and GDH activities were also obtained following inhibition of AsA biosynthesis by lycorine (Lyc) application. By contrast, increased GDH activities and enhanced growth were obtained following exogenous AsA supplementation, with or without JA biosynthesis inhibition.ConclusionsThe findings implied that exogenous JA enhanced AsA biosynthesis and induced GDH activity, which further promoted the growth of wheat seedlings in salt‐stressed conditions. Therefore, the stimulation of AsA biosynthesis and GDH activity through JA application in the rhizosphere may be suggested as a vital strategy for strengthening the salt tolerance of wheat plants, at least at the seedling stage.

Effects of dietary pectin on the growth performance, intestinal barrier, and antioxidant status of juvenile rainbow trout (Oncorhynchus mykiss)

To evaluate the effects of dietary pectin on growth performance, intestinal barrier, and antioxidant status of juvenile rainbow trout (Oncorhynchus mykiss), 10-week feeding trial was conducted. Five isoproteic and isoenergetic diets were formulated to contain 0% (P0), 4% (P4), 8% (P8), and 16% (P16) pectin as well as 0.02% pectinase (PE) at the expense of wheat starch, respectively. Dietary inclusion of 416% pectin linearly promoted the feed intake and growth performance but depressed the feed efficiency, but significant differences were only observed between the P16 and P0 groups. Similarly, dietary inclusion of 816% pectin significantly increased the foregut trypsin and amylase activities but decreased the foregut and midgut sucrase activity. The midgut muc2 gene expression level was significantly down-regulated by the inclusion of 16% pectin. Dietary inclusion of 2% pectin increased the abundance of Proteobacteria and Stenotrophomonas but reduced the abundance of Actinobacteria, Bacteroides and Helicobacter; while the lowest values of observed species, Chao1 and ACE indices of intestinal flora were found in the P8 group. Fish fed with the P8 diet exhibited the lowest plasma catalase and midgut glutathione S-transferase activities as well as malondialdehyde content, but the highest midgut malondialdehyde content. Dietary inclusion of 816% pectin significantly depressed the plasma growth hormone (GH), insulin-like growth factor-1 (IGF-1) and mechanistic target of rapamycin contents as well as alanine aminotransferase activity, the hepatic adenosine monophosphate deaminase and glutamate dehydrogenase (GDH) activities. Dietary treatment with 0.02% pectinase did not affect the growth performance, but depressed the foregut sucrase activity, the midgut amylase and sucrase activities, increased the plasma GH and IGF-1 contents as well as hepatic GDH and aspartate aminotransferase activities. In conclusion, high-dose of dietary pectin (816%) may promote the feed intake and intestinal digestive enzyme activities and thereby improve the growth performance of rainbow trout.

Toxic Trio: Zinc, Copper, and Mercury's Effects on Earthworm Enzymes

The impact of heavy metal exposure on earthworm enzyme activities, specifically lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), malate dehydrogenase (MDH), glutamate dehydrogenase (GDH), xanthine oxidase (XOD), lipid peroxidation, superoxide dismutase (SOD), catalase, and glutathione-S-transferase (GST), was investigated in Perionyx excavatus. In control earthworms, LDH activities were 0.120 µmoles/mg protein/hour in the skin, 0.087 µmoles/mg protein/hour in the ovary, 0.062 µmoles/mg protein/hour in the testis, and 0.096 µmoles/mg protein/hour in the intestine. Exposure to mercuric chloride, copper sulfate, and zinc sulfate resulted in significant decreases in LDH activities by 10% to 19.35%, 4.16% to 22.58%, and 5.74% to 15%, respectively. Similarly, SDH activities declined by 10% to 23% with mercuric chloride, 6.89% to 17.91% with copper sulfate, and 4.13% to 16.66% with zinc sulfate treatments. MDH activities also decreased dramatically across all organs, with statistically significant reductions. GDH activities showed varied responses, while XOD activities uniformly decreased. Lipid peroxidation increased significantly after heavy metal exposure. SOD activities increased with mercuric chloride and copper sulfate, while catalase activities decreased with all three treatments. GST activities were significantly reduced by all treatments, particularly by mercuric chloride and copper sulfate. These findings underscore the substantial impact of heavy metal exposure on earthworm enzyme activities, suggesting potential cellular stress and metabolic disturbances.

Ammoniagenic Action of Valproate without Signs of Hepatic Dysfunction in Rats: Possible Causes and Supporting Evidence.

(1) Background: Valproic acid (VPA) is one of the frequently prescribed antiepileptic drugs and is generally considered well tolerated. However, VPA neurologic adverse effects in the absence of liver failure are fairly common, suggesting that in the mechanism for the development of VPA-induced encephalopathy, much more is involved than merely the exposure to hyperammonemia (HA) caused by liver insufficiency to perform detoxification. Taking into account the importance of the relationship between an impaired brain energy metabolism and elevated ammonia production, and based on the ability of VPA to interfere with neuronal oxidative pathways, the current study intended to investigate a potential regional ammoniagenic effect of VPA on rats' brains by determining activities of the enzymes responsible for ammonia production and neutralization. (2) Methods: Rats received a single intraperitoneal injection of VPA (50, 100, 250, 500 mg/kg). Plasma, the neocortex, the cerebellum, and the hippocampus were collected at 30 min after injection. The levels of ammonia, urea, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were measured in blood plasma. The activities of glutaminase and glutamate dehydrogenase (GDH) in mitochondria and the activities of AMP deaminase (AMPD), adenosine deaminase (ADA), and glutamine synthetase (GS) in cytosolic fractions isolated from rat brain regions were measured. Ammonia, ALT, and AST values were determined in the mitochondrial and cytosolic fractions. (3) Results: Multi-dose VPA treatment did not significantly affect the plasma levels of ammonia and urea or the ALT and AST liver enzymes. Significant dose-independent increases in the accumulation of ammonia were found only in the cytosol from the cerebellum and there was a strong correlation between the ammonia level and the ADA activity in this brain structure. A significant decrease in the AMPD and AST activities was observed, while the ALT activity was unaffected. Only the highest VPA dose (500 mg/kg) was associated with significantly less activity of GS compared to the control in all studied brain structures. In the mitochondria of all studied brain structures, VPA caused a dose-independent increases in ammonia levels, a high concentration of which was strongly and positively correlated with the increased GDH and ALT activity, while glutaminase activity remained unchanged, and AST activity significantly decreased compared to the control in all studied brain structures. (4) Conclusions: This study highlights the rat brain region-specific ammoniagenic effects of VPA, which may manifest themselves in the absence of hyperammonemia. Further research should analyze how the responsiveness of the different brain regions may vary in VPA-treated animals that exhibit compromised energy metabolism, leading to increased ammoniagenesis.

Ammonia assimilation coupled with rapid humification increases recalcitrant nitrogen reservoirs during bioaugmented mechanical composting

The bioaugmented mechanical composting (BMC) of kitchen waste with rapid heating, dehydration, and humification is promising for nitrogen conservation. The combination of ammonia assimilation and rapid humification in BMC may be a distinct nitrogen conservation pathway, converting NH4+-N to recalcitrant organic nitrogen reservoirs. However, questions remain regarding the existence of this pathway and its enhancing mechanism. Thus, nitrogen transformation during a BMC process and a conventional pile composting (CPC) process were compared in this study. Results indicated a significant increase (68.53–75.56%) in the proportion of initial total nitrogen in raw materials preserved in recalcitrant humins in BMC compared to CPC. The significantly higher activity of glutamate dehydrogenase (64.65 ± 7.10 U·mg−1) and glutamine synthase (29.92 ± 3.37 U·mg−1) associated with ammonia assimilation in BMC facilitated the conversion of NH4+ from ammonification into amino acids at the thermophilic phase. These amino acids were then rapidly polymerised with other humic precursors and gradually condensed into heterocyclic and quaternary nitrogen in humins. Further analysis of the bacterial communities and their potential functions revealed that Firmicutes (e.g., Bacillus) and Proteobacteria (e.g., Acinetobacter), which are capable of mineralisation, were enriched by rapid heating and dehydration in BMC. The resulting accumulated NADPH, α-ketoglutaric acid, and humic precursors activated thermophiles associated with ammonia assimilation (e.g., Ureibacillus, Kroppenstedtia, Virgibacillus, and Tepidimicrobium) and humification (e.g., Sacchsromonospora and Bacilli), accelerating nitrogen transformation. This study provides a theoretical foundation for the development of novel nitrogen conservation strategies of coupling ammonia assimilation with rapid humification through enhanced mineralisation during composting.

Identification of candidate genes and residues for improving nitrogen use efficiency in the N-sensitive medicinal plant Panax notoginseng

BackgroundNitrogen (N) metabolism-related key genes and conserved amino acid sites in key enzymes play a crucial role in improving N use efficiency (NUE) under N stress. However, it is not clearly known about the molecular mechanism of N deficiency-induced improvement of NUE in the N-sensitive rhizomatous medicinal plant Panax notoginseng (Burk.) F. H. Chen. To explore the potential regulatory mechanism, the transcriptome and proteome were analyzed and the three-dimensional (3D) information and molecular docking models of key genes were compared in the roots of P. notoginseng grown under N regimes.ResultsTotal N uptake and the proportion of N distribution to roots were significantly reduced, but the NUE, N use efficiency in biomass production (NUEb), the recovery of N fertilizer (RNF) and the proportion of N distribution to shoot were increased in the N0-treated (without N addition) plants. The expression of N uptake- and transport-related genes NPF1.2, NRT2.4, NPF8.1, NPF4.6, AVP, proteins AMT and NRT2 were obviously up-regulated in the N0-grown plants. Meanwhile, the expression of CIPK23, PLC2, NLP6, TCP20, and BT1 related to the nitrate signal-sensing and transduction were up-regulated under the N0 condition. Glutamine synthetase (GS) activity was decreased in the N-deficient plants, while the activity of glutamate dehydrogenase (GDH) increased. The expression of genes GS1-1 and GDH1, and proteins GDH1 and GDH2 were up-regulated in the N0-grown plants, there was a significantly positive correlation between the expression of protein GDH1 and of gene GDH1. Glu192, Glu199 and Glu400 in PnGS1 and PnGDH1were the key amino acid residues that affect the NUE and lead to the differences in GDH enzyme activity. The 3D structure, docking model, and residues of Solanum tuberosum and P. notoginseng was similar.ConclusionsN deficiency might promote the expression of key genes for N uptake (genes NPF8.1, NPF4.6, AMT, AVP and NRT2), transport (NPF1.2 and NRT2.4), assimilation (proteins GS1 and GDH1), signaling and transduction (genes CIPK23, PLC2, NLP6, TCP20, and BT1) to enhance NUE in the rhizomatous species. N deficiency might induce Glu192, Glu199 and Glu400 to improve the biological activity of GS1 and GDH, this has been hypothesized to be the main reason for the enhanced ability of N assimilation in N-deficient rhizomatous species. The key genes and residues involved in improving NUE provide excellent candidates for the breeding of medicinal plants.

Dietary N-carbamylglutamate (NCG) supplementation improves the survival, digestive and immunological parameters by promoting ammonia excretion in Chinese mitten crab (Eriocheir sinensis), under ammonia nitrogen stress

Ammonia nitrogen is one of the most common environmental stress factors in aquaculture. The aim of this experiment was to evaluate the effects of ammonia nitrogen stress on ammonia metabolism, digestion and immune function as well as the protective effects of dietary N-carbamylglutamate (NCG) in the Chinese mitten crab (Eriocheir sinensis). Two feeds were used, namely a control feed (regular commercial feed) and an NCG feed (NCG (302.96 ± 4.07) mg/kg added). Subsequently, animals fed by these two feeds were exposed to 30 mg/L or 60 mg/L ammonia nitrogen stress (named A30 or A60) for 21 days, respectively. The rate of hemolymph ammonia excretion was significantly increased in NCG group compared to C (control) group (P < 0.05). Hemolymph ammonia levels were significantly lower in NCG A30 (NCG feed and A30) and NCG A60 (NCG feed and A60) groups compared to A30 (control feed and A30) and A60 (control feed and A60) groups (P < 0.05). Glutamate dehydrogenase and glutamine synthetase activities in the gills and hepatopancreas of NCG A60 group were significantly increased compared with the A60 group, which promoted glutamine synthesis (P < 0.05). The cumulative mortality rate of Eriocheir sinensis in NCG A30 and NCG A60 groups were effectively reduced (P < 0.05). The arginine levels of hepatopancreas were significantly increased in NCG A60 group (P < 0.05). Under ammonia nitrogen stress, NCG significantly increased the activities of trypsin, pepsin, lipase and α-Amylase in NCG feed group, and promoted feeding (P < 0.05). In hemolymph, hepatopancreas and intestine, NCG significantly increased nitric oxide synthase activity, lysozyme and phenol oxidase activities compared to the ammonia nitrogen stress group (P < 0.05). The results indicated that, NCG added in feed could decelerate the toxic effects of ammonia on Eriocheir sinensis by promoting ammonia excretion and accelerating glutamine and endogenous arginine synthesis by metabolism. Moreover, the activity of digestive enzymes and immune-related enzymes is improved.

Surviving winter on the Qinghai-Xizang Plateau: Extensive reversible protein phosphorylation plays a dominant role in regulating hypometabolism in hibernating Nanorana parkeri.

Changes in protein abundance and reversible protein phosphorylation (RPP) play important roles in regulating hypometabolism but have never been documented in overwintering frogs at high altitudes. To test the hypothesis that protein abundance and phosphorylation change in response to winter hibernation, we conducted a comprehensive and quantitative proteomic and phosphoproteomic analysis of the liver of the Xizang plateau frog, Nanorana parkeri, living on the Qinghai-Xizang (Tibet) Plateau (QTP). In total, 5 170 proteins and 5 695 phosphorylation sites in 1 938 proteins were quantified. Based on proteomic analysis, 674 differentially expressed proteins (438 up-regulated, 236 down-regulated) were screened in hibernating N. parkeri versus summer individuals. Functional enrichment analysis revealed that higher expressed proteins in winter were significantly enriched in immune-related signaling pathways, whereas lower expressed proteins were mainly involved in metabolic processes. A total of 4 251 modified sites (4 147 up-regulated, 104 down-regulated) belonging to 1 638 phosphoproteins (1 555 up-regulated, 83 down-regulated) were significantly changed in the liver. During hibernation, RPP regulated a diverse array of proteins involved in multiple functions, including metabolic enzymatic activity, ion transport, protein turnover, signal transduction, and alternative splicing. These changes contribute to enhancing protection, suppressing energy-consuming processes, and inducing metabolic depression. Moreover, the activities of phosphofructokinase, glutamate dehydrogenase, and ATPase were all significantly lower in winter compared to summer. In conclusion, our results support the hypothesis and demonstrate the importance of RPP as a regulatory mechanism when animals transition into a hypometabolic state.

Source-sink coordinated peanut cultivar increases yield and kernel protein content through enhancing photosynthetic characteristics and regulating carbon and nitrogen metabolisms

The grain yield of crops is determined by the synergistic interaction between source activity and sink capacity. However, source-sink interactions are far from being fully understood of peanut. Therefore, a 2-year field study (2018–2019) was conducted to compare differences in photosynthetic characteristics, carbon and nitrogen metabolism, and yield and quality of different source–sink peanut varieties. Four representative source–sink types were examined: JH5 (source–sink coordination type), SH9 (sufficient source–large sink type), ZH24 (sufficient source–few sink type), and HY36 (large source–few sink type). The results showed that the photosynthetic potential of HY36 was higher than that of the other varieties after flowering because of a large source (leaves), whereas the chlorophyll content and net photosynthetic rate of HY36 were significantly lower than those of JH5 and ZH24. Proportions of dry matter transferred to pods were significantly different among four source–sink peanut varieties. From 50 days after flowering, the dry matter distribution ratio of pods exceeded that of stems and leaves in JH5, significantly earlier than other varieties, which prolong the duration of pod-filling period, followed by SH9 and ZH24. The activities of nitrate reductase, glutamine synthetase, glutamate dehydrogenase, and glutamate synthase in JH5 were the highest among the varieties, and thus, the highest protein content was also in JH5. The activities of sucrose synthase and sucrose phosphate synthase in ZH24 were significantly higher than those in HY36. The highest oil content was also in ZH24. Among pod sink characteristics and yield, SH9 had the longest flowering period and the highest gynophore formation rate but the lowest pod-bearing rate, and the effective proportion and pod fullness were also lower than those of other varieties. The highest pod rate was in ZH24. The effective proportion and pod fullness of JH5 were higher than those of the other varieties, and its yield was also the highest, followed by SH9 and ZH24, with the lowest yield in HY36. The obtained results indicate that the source–sink coordinated variety had high Pn and chlorophyll content in the late growth stage, a long functional period of leaves, and a high proportion of assimilates transported to pods, thus promoting effective proportions and pod fullness to improve peanut yield and protein content, suggesting that different cultivation and management measures should select for different peanut varieties to best coordinate the relationship between the source and sink.

Integrated comparative transcriptome and physiological analysis reveals the metabolic responses underlying genotype variations in NH4+ tolerance.

Several mechanisms have been proposed to explain NH4 + toxicity. However, the core information about the biochemical regulation of plants in response to NH4 + toxicity is still lacking. In this study, the tissue NH4 + concentration is an important factor contributing to variations in plant growth even under nitrate nutrition and NH4 + tolerance under ammonium nutrition. Furthermore, NH4 + led to the reprogramming of the transcriptional profile, as genes related to trehalose-6-phosphate and zeatin biosynthesis were downregulated, whereas genes related to nitrogen metabolism, camalexin, stilbenoid and phenylpropanoid biosynthesis were upregulated. Further analysis revealed that a large number of genes, which enriched in phenylpropanoid and stilbenoid biosynthesis, were uniquely upregulated in the NH4 +- tolerant ecotype Or-1. These results suggested that the NH4 +-tolerant ecotype showed a more intense response to NH4 + by activating defense processes and pathways. Importantly, the tolerant ecotype had a higher 15NH4 + uptake and nitrogen utilization efficiency, but lower NH4 +, indicating the tolerant ecotype maintained a low NH4 + level, mainly by promoting NH4 + assimilation rather than inhibiting NH4 + uptake. The carbon and nitrogen metabolism analysis revealed that the tolerant ecotype had a stronger carbon skeleton production capacity with higher levels of hexokinase, pyruvate kinase, and glutamate dehydrogenase activity to assimilate free NH4 +, Taken together, the results revealed the core mechanisms utilized by plants in response to NH4 +, which are consequently of ecological and agricultural importance.

Evaluation of the Moonlighting Histone H3 Specific Protease (H3ase) Activity and the Dehydrogenase Activity of Glutamate Dehydrogenase (GDH).

The N-terminus of Histone H3 is proteolytically processed in aged chicken liver. A histone H3 N-terminus specific endopeptidase (named H3ase) has been purified from the nuclear extract of aged chicken liver. By sequencing and a series of biochemical methods including the demonstration of H3ase activity in bacterially expressed GDH, it was established that the H3ase activity was a moonlighting protease activity of glutamate dehydrogenase (GDH). However, the active site for the H3ase in the GDH remains elusive. Here, using cross-linking studies of the homogenously purified H3ase, we show that the GDH and the H3ase remain in the same native state. Further, the H3ase and GDH activities could be uncoupled by partial denaturation of GDH, suggesting strong evidence for the involvement of different active sites for GDH and H3ase activities. Through densitometry of the H3ase clipped H3 products, the H3ase activity was quantified and it was compared with the GDH activity of the chicken liver nuclear GDH. Furthermore, the H3ase mostly remained distributed in the perinuclear area as demonstrated by MNase digestion and immuno-localization of H3ase in chicken liver nuclei, as well as cultured mouse hepatocyte cells, suggesting that H3ase demonstrated regulated access to the chromatin. The present study thus broadly compares the H3ase and GDH activities of the chicken liver GDH.

Is there any robust evidence showing that SGLT2 inhibitor predisposes to cancer?

The exact pathophysiological mechanisms of SGLT-2 inhibitors in the development, progression or treatment of malignancies are not fully understood, but multiple hypotheses have been proposed. SGLT-2 inhibitors have potential anti-proliferative roles due to several underlying pathophysiological mechanisms, such as inhibition of ATP production, activation of AMPK signalling, induction of apoptosis and ferroptosis, inhibition of glutamate dehydrogenase activity and inhibition of DNA and RNA synthesis. However, heterogeneity among tumour cells and SGLT-2 inhibitor drugs limit the generalizability of pre-clinical studies. This is a narrative review discussing the potential anti-cancer effects of SGLT-2 inhibitors, an oral glucose-lowering medication used in patients with type II diabetes mellitus. This review discusses underlying mechanisms, pre-clinical and clinical trial data, epidemiological data and future perspectives on the use of SGLT-2 inhibitors in cancer treatment. Type II diabetes is linked to various comorbidities and malignancies, but some glucose-slowering medications may have a preventive role in cancer. The use of SGLT-2 inhibitors was associated with bladder cancer based on mice studies. However, meta-analyses showed no significant increase in overall malignancy incidence of any specific type, except for empagliflozin and bladder cancer association. SGLT-2 inhibitors can potentially reduce the heart damage caused by doxorubicin and sunitinib, while enhancing the anti-cancer effects of doxorubicin. Combining SGLT-2 inhibitors with doxorubicin may allow higher doses of chemotherapy use. Multiple ongoing clinical trials are investigating the potential therapeutic potential of SGLT-2 inhibitors in various types of cancer. More large-scale pre-clinical and clinical studies are needed to explore their potential preventive and therapeutic roles of SGLT-2 inhibitors in cancer treatment. In this narrative review, our aim is to explore the pre-clinical and clinical data regarding the potential anti-cancer effects of SGLT-2 inhibitors including the hypothetical pathophysiological mechanisms.

Use of black soldier fly (Hermetia illucens) larvae meal in diets for gilthead seabream juveniles: Effects on growth-related gene expression, intermediary metabolism, digestive enzymes, and gut microbiota modulation

A study was conducted to evaluate the effects of dietary inclusion of defatted Hermetia illucens larvae meal (HM) on the expression of growth-related genes, plasma metabolites, activity of intermediary metabolism enzymes, and gut microbiota modulation in gilthead seabream (Sparus aurata) juveniles. Four experimental diets were formulated (43% crude protein, 18% crude lipids) with increasing levels of defatted HM: 0 (HM0), 15 (HM15), 30 (HM30), and 45% (HM45) replacing fishmeal (included at 34% in the control diet) at 0, 22, 60, and 100%, respectively. Fish were fed these diets for 67 days. At the end of the trial, the expression of muscle growth hormone receptors (ghr1 and ghr2), insulin-like growth factors (igf1 and igf2), cathepsins (cts-a and cts-b), and myogenic determination factor 1 (myod1) were not affected, while a downregulation of myogenic determination factor 2 (myod2) and upregulation of myostatin (mstn) was observed with HM inclusion. Plasma metabolites profile was unaffected by diet composition, except for a linear decrease trend in total lipids. A linear increase of liver alanine aminotransferase (ALT) and glutamate dehydrogenase (GDH) activity and a linear decrease of glucose 6-phosphate dehydrogenase (G6PDH), malic enzyme (ME), and (FAS) activity were observed with HM inclusion. The activity of β-hydroxy acyl-CoA dehydrogenase (HOAD) followed a quadratic trend, being higher in fish fed with diet HM15 than in the control. Likewise, amylase, trypsin, and chymotrypsin activity were higher in the posterior intestine of fish fed with diet HM15. Digesta of fish fed the HM-containing diets showed an increase in the number of operational taxonomic units, microbial richness, and diversity. Conversely, a reduction in these indexes was observed in the mucosa. Among the identified bacteria, Firmicutes represented the predominant phyla. The inclusion of HM increased the abundance of Oceanobacillus, Lederbergia, Bacillus, and Corynebacterium in the digesta while Lactobacillus and Caldalkalibacillus abundance was reduced. Overall, total FM replacement with defatted HM had no major effects on plasma metabolites and muscle growth-related genes but induced a few differences in intermediary metabolism and digestive enzymes activity. HM inclusion improved gut digesta microbiota richness and diversity, promoting the growth of potential beneficial bacteria.

LED red and blue light intensity affected productivity and nitrogen metabolisms of ryegrass

Light intensity plays a critical regulatory role in determining plant yield and quality, and energy consumption in plant factory with artificial light (PFAL). The effects of different light intensities (200, 300, 400, 500, and 600 µmol·m−2·s−1) of light-emitting diodes (LED) red and blue light with ratio 4:1 on growth, quality, nitrogen and amino acid metabolisms of ryegrass were investigated. The results showed the tiller number and shoot fresh weight in ryegrass were increased, while plant height and stem diameter remained stable with the improvement of light intensity. The highest levels of soluble protein, free amino acid, and DPPH free radical clearance rate in photon flux density (PPFD) at 500 µmol·m−2·s−1, and then significantly decreased with light intensity increased. The highest soluble sugar content was found at PPFD of 600 µmol·m−2·s−1, while malondialdehyde (MDA) content remained stable in all treatments. As the light intensity increased, nitrate content decreased, while nitrate reductase (NR) activity and the ammonium content increased. As light intensity was increased from 200 to 600 µmol·m−2·s−1, nitrite reductase (NiR) activity first decreased and then increased. Moreover, glutamate and cysteine contents increased first and then decreased, while glutamate synthase (GOGAT), glutamine synthase (GS), glutamate dehydrogenase (GDH), and cysteine synthases (CS) activities increased continuously with light intensity. Light intensity was significantly correlated with the parameters of growth, quality, nitrogen and amino acid metabolisms in ryegrass. It was recommended that PPFD at 400–500 µmol·m−2·s−1, photoperiod of 16 h/d was suitable for ryegrass high-efficient production in PFAL with relatively low energy cost.

A comparative analysis of fruit fly and human glutamate dehydrogenases in Drosophila melanogaster sperm development.

Glutamate dehydrogenases are enzymes that take part in both amino acid and energy metabolism. Their role is clear in many biological processes, from neuronal function to cancer development. The putative testis-specific Drosophila glutamate dehydrogenase, Bb8, is required for male fertility and the development of mitochondrial derivatives in spermatids. Testis-specific genes are less conserved and could gain new functions, thus raising a question whether Bb8 has retained its original enzymatic activity. We show that while Bb8 displays glutamate dehydrogenase activity, there are significant functional differences between the housekeeping Gdh and the testis-specific Bb8. Both human GLUD1 and GLUD2 can rescue the bb8 ms mutant phenotype, with superior performance by GLUD2. We also tested the role of three conserved amino acids observed in both Bb8 and GLUD2 in Gdh mutants, which showed their importance in the glutamate dehydrogenase function. The findings of our study indicate that Drosophila Bb8 and human GLUD2 could be novel examples of convergent molecular evolution. Furthermore, we investigated the importance of glutamate levels in mitochondrial homeostasis during spermatogenesis by ectopic expression of the mitochondrial glutamate transporter Aralar1, which caused mitochondrial abnormalities in fly spermatids. The data presented in our study offer evidence supporting the significant involvement of glutamate metabolism in sperm development.