Journal articles on the topic 'Phosphoenol pyruvate kinase (PEPCK)'
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1
Lewitt, MS, K. Brismar, J. Ohlson, and J. Hartman. "Lithium chloride inhibits the expression and secretion of insulin-like growth factor-binding protein-1." Journal of Endocrinology 171, no. 3 (December 1, 2001): R11—R15. http://dx.doi.org/10.1677/joe.0.171r011.
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Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates IGF availability for glucose homeostasis. The IGFBP-1 promoter shares common regulatory response elements with phosphoenol pyruvate carboxykinase (PEPCK), the expression and activity of which is inhibited by lithium chloride, associated with an inhibition of glycogen synthase kinase (GSK)-3 activity, in the rat hepatoma cell line H4-II-E. We therefore determined the effect of lithium chloride on IGFBP-1 expression and secretion in H4-II-E cells. Lithium chloride inhibited IGFBP-1 secretion in a dose response and reversible manner by approx 80% during 5-h and 16-h incubations. An inhibitory effect on IGFBP-1 mRNA expression was observed at 2 h. The inhibitory effect of lithium and insulin were not additive when used alone, but inhibition by lithium occurred when insulin action was blocked by activating AMP-activated protein kinase with 5-aminoimidazole-4-carboxamide-riboside (AICAR). These findings suggest that GSK-3 inhibition, or another pathway activated by lithium, may be involved in a pathway controlling IGFBP-1, inhibiting synthesis when insulin activity is absent or impaired.
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Jones, C. G., and M. A. Titheradge. "The effect of treatment of the rat with bacterial endotoxin on gluconeogenesis and pyruvate metabolism in subsequently isolated hepatocytes." Biochemical Journal 289, no. 1 (January 1, 1993): 169–72. http://dx.doi.org/10.1042/bj2890169.
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The effect of treatment of rats with bacterial endotoxin on gluconeogenesis and the flux through pyruvate kinase, phosphoenolpyruvate carboxykinase (PEPCK), pyruvate carboxylase and pyruvate dehydrogenase (PDH) was measured in isolated hepatocytes, prepared from animals starved for 18 h, incubated in the presence of 1 mM pyruvate. The lipopolysaccharide reduced gluconeogenesis by 50% and lowered the flux through pyruvate kinase, PEPCK and pyruvate carboxylase by comparable amounts. There was no effect of endotoxaemia on PDH flux, indicating that the lowered rate of gluconeogenesis is not the result of a redistribution of pyruvate metabolism between oxidation and carboxylation. The results confirm that a stimulation of pyruvate kinase activity following treatment with lipopolysaccharide is not involved in the inhibition of gluconeogenesis, but that the effect resides at the level of phosphoenolpyruvate formation. The most favoured mechanism for the inhibition of glucose synthesis is via an inhibition of PEPCK and subsequent feedback inhibition of pyruvate carboxylase, although a secondary effect at the level of the mitochondria and pyruvate carboxylase cannot be excluded.
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Zelle, Rintze M., Josh Trueheart, Jacob C. Harrison, Jack T. Pronk, and Antonius J. A. van Maris. "Phosphoenolpyruvate Carboxykinase as the Sole Anaplerotic Enzyme in Saccharomyces cerevisiae." Applied and Environmental Microbiology 76, no. 16 (June 25, 2010): 5383–89. http://dx.doi.org/10.1128/aem.01077-10.
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ABSTRACT Pyruvate carboxylase is the sole anaplerotic enzyme in glucose-grown cultures of wild-type Saccharomyces cerevisiae. Pyruvate carboxylase-negative (Pyc−) S. cerevisiae strains cannot grow on glucose unless media are supplemented with C4 compounds, such as aspartic acid. In several succinate-producing prokaryotes, phosphoenolpyruvate carboxykinase (PEPCK) fulfills this anaplerotic role. However, the S. cerevisiae PEPCK encoded by PCK1 is repressed by glucose and is considered to have a purely decarboxylating and gluconeogenic function. This study investigates whether and under which conditions PEPCK can replace the anaplerotic function of pyruvate carboxylase in S. cerevisiae. Pyc− S. cerevisiae strains constitutively overexpressing the PEPCK either from S. cerevisiae or from Actinobacillus succinogenes did not grow on glucose as the sole carbon source. However, evolutionary engineering yielded mutants able to grow on glucose as the sole carbon source at a maximum specific growth rate of ca. 0.14 h−1, one-half that of the (pyruvate carboxylase-positive) reference strain grown under the same conditions. Growth was dependent on high carbon dioxide concentrations, indicating that the reaction catalyzed by PEPCK operates near thermodynamic equilibrium. Analysis and reverse engineering of two independently evolved strains showed that single point mutations in pyruvate kinase, which competes with PEPCK for phosphoenolpyruvate, were sufficient to enable the use of PEPCK as the sole anaplerotic enzyme. The PEPCK reaction produces one ATP per carboxylation event, whereas the original route through pyruvate kinase and pyruvate carboxylase is ATP neutral. This increased ATP yield may prove crucial for engineering of efficient and low-cost anaerobic production of C4 dicarboxylic acids in S. cerevisiae.
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Radiati, Lilik Eka, Dian Laksamana Hati, Sri Andarini, Dian Handayani, and Djalal Rosyidi. "Potensi Whey Kefir Susu Kambing Sebagai Anti-Obesitas Melalui Penghambatan Sintesis Lipid dan Aktivitas Phosphoenolpyruvate Carboxykinase (PEPCK) pada Sel Model Adiposit 3T3-L1." Indonesian Journal of Human Nutrition 9, no. 2 (December 30, 2022): 207. http://dx.doi.org/10.21776/ub.ijhn.2022.009.02.9.
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Obesitas menjadi salah satu penyebab utama sindrom metabolik dislipidemia, yang dapat sebagai komorbid berbagai penyakit. Penggunaan obat-obatan untuk mengurangi obesitas memiliki akibat yang merugikan, oleh karena itu dikembangkan produk komplementer dari susu fermentasi sebagai strategi non-farmakologis untuk pengelolaan dislipidemia. Pemecahan masalah obesitas dapat dilakukan melalui pendekatan adipogenesis pada sel model adiposit 3T3-L1. Tujuan penelitian ini adalah menganalisis pemberian whey-KSK terhadap TG (Total Trigliserida), TC (Total Kolesterol) dan aktivitas PEPCK (Phosphoenol pyruvate Carboxykinase) sel adiposit 3T3-L1. Metode penelitian adalah percobaan pemberian dosis whey-KSK yang berbeda yaitu P1 (25mg/ml), P2 (50 mg/ml), P3 (75 mg/ml), P4 (100 mg/ml), dan kelompok KN (kontrol negatif) dan KP (kontrol positif) pada adiposit 3T3-L1, dengan empat kali ulangan. Hasil penelitian menunjukkan whey-KSK 25 – 100 µg/mL dapat menurunkan TG sebesar 35,39 – 55,32%, menurunkan TC sebesar 30,46-62,12%, menurunkan aktivitas PEPCK sebesar 27,10-82,52% dan menurunkan aktivitas spesifik PEPCK sebesar 33,06-63,34%. Kesimpulan whey-KSK dapat menghambat adipogenesis sel adiposit 3T3-L1 dan berpotensi sebagai antiobesitas.
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Hosagoudar, V. B. "Computational Screening Of Phytochemicals To Block Phosphoenol Pyruvate Carboxykinase (Pepck) ,A Key Enzyme In Glucose Metabolism." Scientific Transactions in Enviornment and Technovation 4, no. 2 (December 15, 2010): 89–91. http://dx.doi.org/10.20894/stet.116.004.002.008.
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Bizeau, Michael E., Chiffon Short, Jeffrey S. Thresher, S. Renee Commerford, Wayne T. Willis, and Michael J. Pagliassotti. "Increased pyruvate flux capacities account for diet-induced increases in gluconeogenesis in vitro." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 281, no. 2 (August 1, 2001): R427—R433. http://dx.doi.org/10.1152/ajpregu.2001.281.2.r427.
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High-fat (HF) and high-sucrose (SU) diets increase gluconeogenesis. The present study was designed to determine the contributions of pyruvate dehydrogenase, pyruvate carboxylase, phospho enolpyruvate carboxykinase (PEPCK), and pyruvate kinase fluxes to this accelerated gluconeogenesis (GNEO) in the absence and presence of fatty acids. Male Sprague-Dawley rats were fed an HF, SU, or starch (ST) diet for 1 wk, and hepatocytes or mitochondria were isolated. In the absence of palmitate, the tracer estimated rates of GNEO (nmol · min−1 · mg−1) were elevated in hepatocytes isolated from SU (32.3 ± 1.8) and HF (35.4 ± 1.8) vs. ST (22.8 ± 1.5). Pyruvate carboxylase and PEPCK flux rates (nmol · min−1 · mg−1) were increased in the SU (47.5 ± 2.2 and 34.8 ± 1.5) and HF (49.4 ± 1.8 and 38.2 ± 1.8) groups compared with the ST group (32.8 ± 3.2 and 44.3 ± 2.0). Palmitate (250–1,000 μM) stimulation of these fluxes was not significantly different among groups. Bromopalmitate, an inhibitor of fat oxidation, abolished differences in GNEO, pyruvate carboxylase, and PEPCK fluxes in HF and SU vs. ST. In isolated mitochondria, pyruvate carboxylation and palmitoyl carnitine oxidation were not significantly different among groups. The results of this study suggest that the increased gluconeogenic flux observed with HF and SU diets is associated with an increased pyruvate flux through pyruvate carboxylase and PEPCK. Moreover, the ability of bromopalmitate to normalize gluconeogenic fluxes suggests that endogenous fatty acids contribute to diet-induced increases in GNEO.
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Nizielski, S. E., C. Arizmendi, A. R. Shteyngarts, C. J. Farrell, and J. E. Friedman. "Involvement of transcription factor C/EBP-beta in stimulation of PEPCK gene expression during exercise." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 270, no. 5 (May 1, 1996): R1005—R1012. http://dx.doi.org/10.1152/ajpregu.1996.270.5.r1005.
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Prolonged exercise increases gluconeogenesis and activates transcription of the hepatic phosphoenol pyruvate carboxykinase (PEPCK) gene. The mechanisms that regulate the transcriptional control of gene expression depend on the interaction of nuclear proteins with distinct DNA sequences. To determine the involvement with the liver-enriched transcription factor CCAAT/enhancer binding protein beta (C/EMP-beta) in the induction of PEPCK gene transcription during prolonged exercise or adenosine 3',5'-cyclic monophosphate (cAMP) treatment, we examined C/EBP-beta mRNA and nuclear protein concentrations, as well as C/EBP-beta binding to the PEPCK promoter at the cAMP response element (CRE)(-87/-74) and P3I (-248/-230) binding sites. The requirement of these DNA elements for exercise-induced stimulation of PEPCK gene expression was established in transgenic mice carrying -460 +/- 73 of the PEPCK promoter with a mutation in either the CRE or P3I binding domain linked to a bovine growth hormone (bGH) reporter gene. In mice carrying the intact promoter, prolonged exercise increased the concentration of liver bGH mRNA by 510% compared with an increase of only 270% in mice with a mutation in either the CRE or P3I site. Exercise or cAMP injection induced a 7.5- and 13-fold increase in nuclear C/EBP-beta protein, respectively. In electrophoretic mobility shift assays (EMSA), the total quantity of nuclear proteins bound to either oligomer was not altered by treatment. However, addition of C/EBP-beta antisera in the EMSA in a supershift assay indicated that liver nuclear extracts from exercised or cAMP-treated mice demonstrated significantly greater DNA binding due to C/EBP-beta (CRE: control 44.4 +/- 2.3%, exercise 56.7% +/- 2.2%, cAMP 54.5 +/- 3.6% of total binding, P < 0.001; P3I: control 35.8 +/- 2.5%, exercise 64.9 +/- 1.9%, cAMP 57.3 +/- 2.5% of total binding, P < 0.001). Taken together, these results suggest that exercise and cAMP treatment induce a transient increase in C/EBP-beta that may contribute to the molecular mechanism for signaling PEPCK gene transcription and increasing gluconeogenesis during exercise.
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O'Brien, R. M., R. S. Streeper, J. E. Ayala, B. T. Stadelmaier, and L. A. Hornbuckle. "Insulin-regulated gene expression." Biochemical Society Transactions 29, no. 4 (August 1, 2001): 552–58. http://dx.doi.org/10.1042/bst0290552.
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Insulin regulates the expression of more than 150 genes, indicating that this is a major action of this hormone. At least eight distinct consensus insulin response sequence (IRSs) have been defined through which insulin can regulate gene transcription. These include the serum response element, the activator protein 1 (‘AP-1’) motif, the Ets motif, the E-box motif and the thyroid transcription factor 2 (‘TTF-2’) motif. All of these IRSs mediate stimulatory effects of insulin on gene transcription. In contrast, an element with the consensus sequence T(G/A)TTT(T/G)-(G/T), which we refer to as the phosphoenol-pyruvate carboxykinase (PEPCK)-like motif, mediates the inhibitory effect of insulin on transcription of the genes encoding PEPCK, insulinlike-growth-factor-binding protein 1 (IGFBP-1), tyrosine aminotransferase and the glucose-6-phos-phatase (G6Pase) catalytic subunit. The forkhead transcription factor FKHR has recently been shown to bind this PEPCK-like IRS motif and a model has been proposed in which insulin inhibits gene transcription by stimulating the phosphorylation and nuclear export of FKHR. Our results suggest that this model is consistent with the action of insulin on transcription of the gene encoding IGFBP-1 but not that of the G6Pase catalytic subunit. Thus, even though the IRSs in both promoters seem identical, they are functionally distinct. In addition, in the G6Pase catalytic subunit promoter, hepatocyte nuclear factor 1 (‘HNF-1’), acts as an accessory factor to enhance the effect of insulin mediated through the IRS.
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Tielens, A. G. M., P. Van Der Meer, J. M. Van Den Heuvel, and S. G. Van Den Bergh. "The enigmatic presence of all gluconeogenic enzymes in Schistosoma mansoni adults." Parasitology 102, no. 2 (April 1991): 267–76. http://dx.doi.org/10.1017/s0031182000062582.
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SUMMARYThe activities of glucose-6-phosphatase (G6Pase), frucrose-1,6-bisphosphatase (FBPase), phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate carboxylase (PC) were determined in homogenates of adult Schistosoma mansoni worms and compared with the activities in homogenates of rat liver and rat skeletal muscle, tissues with a high and a low gluconeogenic capacity, respectively. All four gluconeogenic enzymes were present in S. mansoni. The enzymes were less active than in rat liver, but the activities of G6Pase, PEPCK and PC were at least an order of magnitude higher than in rat skeletal muscle whereas FBPase was approximately equally active in S. mansoni and in rat muscle. Experiments with 14C-labelled substrates or [14C]NaHCO3 failed to demonstrate the actual occurrence of gluconeogenesis in S. mansoni. Some possible other functions of the gluconeogenic enzymes were investigated. Experiments with inhibitors of PEPCK gave no indications that this enzyme was involved in the degradation of glucose. This was confirmed by 13C-NMR experiments which indicated that lactate was formed from phosphoenolpyruvate via the actions of pyruvate kinase and lactate dehydrogenase, and that PEPCK did not participate in the formation of lactate. Substrate cycling between fructose-6-phosphate and fructose-1,6-bisphosphate was demonstrated to occur in adult S. mansoni. This shows that FBPase participates in the glucose metabolism of this parasite.
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Christie, Daphne A., John W. Powell, Jeremy N. Stables, and Robert A. Watt. "A nuclear magnetic resonance study of the role of phosphoenol pyruvate carboxykinase (PEPCK) in the glucose metabolism of Dipetalonema viteae." Molecular and Biochemical Parasitology 24, no. 2 (June 1987): 125–30. http://dx.doi.org/10.1016/0166-6851(87)90098-3.
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Echevarría, Cristina, Jean Vidal, Jin-an Jiao, and Raymond Chollet. "Reversible light activation of the phosphoenol pyruvate carboxylase protein-serine kinase in maize leaves." FEBS Letters 275, no. 1-2 (November 26, 1990): 25–28. http://dx.doi.org/10.1016/0014-5793(90)81430-v.
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Mohammad, Sameer, Asia Taha, Kamal Akhtar, R. N. K. Bamezai, and Najma Zaheer Baquer. "In vivo effect of Trigonella foenum graecum on the expression of pyruvate kinase, phosphoenolpyruvate carboxykinase, and distribution of glucose transporter (GLUT4) in alloxan-diabetic rats." Canadian Journal of Physiology and Pharmacology 84, no. 6 (June 2006): 647–54. http://dx.doi.org/10.1139/y05-164.
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Plasma glucose levels are maintained by a precise balance between glucose production and its use. Liver pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK), 2 key enzymes of glycolysis and gluconeogenesis, respectively, play a crucial role in this glucose homeostasis along with skeletal muscle glucose transporter (GLUT4). In the diabetic state, this balance is disturbed owing to the absence of insulin, the principal factor controlling this regulation. In the present study, alloxan-diabetic animals having high glucose levels of more than 300 mmol/L have been taken and the administration of Trigonella seed powder (TSP) to the diabetic animals was assessed for its effect on the expression of PK and PEPCK in liver and GLUT4 distribution in skeletal muscle of alloxan-diabetic rats. TSP treatment to the diabetic animals resulted in a marked decrease in the plasma glucose levels. Trigonella treatment partially restored the altered expression of PK and PEPCK. TSP treatment also corrected the alterations in the distribution of GLUT4 in the skeletal muscle.
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Xavier, Analúcia Rampazzo, José Eduardo de Salles Roselino, Neusa Maria Zanon Resano, Maria Antonieta Rissato Garófalo, Renato Helios Migliorini, and Isis do Carmo Kettelhut. "Glyconeogenic pathway in isolated skeletal muscles of rats." Canadian Journal of Physiology and Pharmacology 80, no. 2 (February 1, 2002): 162–67. http://dx.doi.org/10.1139/y02-013.
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Although the conversion of lactate to glycogen (glyconeogenesis) in muscle was demonstrated a long time ago, the biochemical reactions responsible for this process are still a controversial matter. In the present study, advantage was taken from the specific inhibition induced by phenylalanine on muscle pyruvate kinase (PK) to investigate the role of reverse PK activity in muscle glyconeogenesis. Addition of phenylalanine to the incubation medium of a preparation of isolated, intact skeletal muscles that maintain metabolic activity for several hours reduced by 50% the rate of incorporation of [14C]lactate or [14C]bicarbonate into muscle glycogen. Muscle extracts presented high levels of maximal activity of PK in the reverse direction, which was completely blocked in the presence of phenylalanine. In contrast, mercaptopicolinic acid, an inhibitor of phosphoenolpyruvate carboxykinase (PEPCK), did not affect the incorporation of14C from either lactate or bicarbonate into muscle glycogen. Maximal PEPCK activity was much lower in muscle extracts than in gluconeogenic or glyceroneogenic tissues and was suppressed in the presence of mercaptopicolinic acid. The data suggest that a reversal of the metabolic flux through the reaction catalyzed by PK contributes to the accumulation of lactate-derived glycogen that occurs in skeletal muscle under certain physiological conditions.Key words: lactate, glyconeogenesis, skeletal muscle, reverse pyruvate kinase reaction, phenylalanine.
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Tsuchida, Yuhei, Tsuyoshi Furumoto, Atsushi Izumida, Shingo Hata, and Katsura Izui. "Phosphoenol pyruvate carboxylase kinase involved in C4 photosynthesis in Flaveria trinervia : cDNA cloning and characterization1." FEBS Letters 507, no. 3 (November 2, 2001): 318–22. http://dx.doi.org/10.1016/s0014-5793(01)02994-5.
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Ou, J., L. Molina, Y. M. Kim, and T. R. Billiar. "Excessive NO production dose not account for the inhibition of hepatic gluconeogenesis in endotoxemia." American Journal of Physiology-Gastrointestinal and Liver Physiology 271, no. 4 (October 1, 1996): G621—G628. http://dx.doi.org/10.1152/ajpgi.1996.271.4.g621.
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The pattern of inhibition of gluconeogenesis in hepatocytes was compared between endotoxemia in vivo and nitric oxide (NO) exposure in vitro. Fasted rats were injected with lipopolysaccharide (LPS; 12 mg/kg) or with vehicle alone. After 2-24 h, hepatocytes were isolated, placed in suspension, and incubated for 1 h with various gluconeogenic substrates that enter at different sites of the gluconeogenic pathway. Hepatocytes from LPS-treated rats exhibited up to a 50% decrease in gluconeogenesis for substrates that enter proximal to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) beginning at 6 h, followed by a nadir at 12 h after LPS. Although hepatocytes exposed to exogenous NO (S-nitroso-N-acetylpenicillamine) also exhibited a depressed gluconeogenesis, the pattern was not the same with inhibition in gluconeogenesis for substrates that enter the pathway both before and after GAPDH. Furthermore, when rats injected with LPS were subjected to a constant portal infusion (Alzet pump) of the NO synthase (NOS) inhibitors, NG-monomethyl-L-arginine or aminoguanidine, no changes in the LPS-induced gluconeogenesis suppression were seen. In addition, no difference in LPS-induced inhibition of gluconeogenesis was detected when hepatocytes from inducible NO synthase (NOS-2) knockout mice were compared with cells obtained from wild-type mice. Minimal decreases in GAPDH activity were measured in hepatocytes from the LPS-treated rats, whereas the activity of phosphoenol pyruvate carboxykinase (PEPCK) declined up to 40%, independent of NO synthesis. These data indicate that NO does not account for the inhibition of gluconeogenesis in endotoxemia, and they provide support for NO-independent reduction in PEPCK activity as a more plausible explanation.
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Forest, C., J. Tordjman, M. Glorian, E. Duplus, G. Chauvet, J. Quette, E. G. Beale, and B. Antoine. "Fatty acid recycling in adipocytes: a role for glyceroneogenesis and phosphoenolpyruvate carboxykinase." Biochemical Society Transactions 31, no. 6 (December 1, 2003): 1125–29. http://dx.doi.org/10.1042/bst0311125.
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FA (fatty acid) recycling in adipose tissue appears to be an important pathway for regulating FA release into the blood during fasting. Re-esterification requires G3P (glycerol 3-phosphate), which cannot be synthesized from glucose because glycolysis is much reduced under such circumstances. In addition, G3P can scarcely originate from glycerol since glycerol kinase has a very low activity in white adipose tissue. It was shown about 35 years ago that a metabolic pathway named glyceroneogenesis, which allows G3P synthesis from non-carbohydrate precursors like pyruvate, lactate or amino acids, is activated during fasting. The major enzyme in this pathway was shown to be PEPCK-C [cytosolic phosphoenolpyruvate carboxykinase (GTP); EC 4.1.1.32]. The present review analyses the mechanisms by which a series of hormones and nutrients affect PEPCK-C gene transcription and glyceroneogenesis and describes evidence for dysregulation of this pathway in type 2 diabetes.
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Onwuliri, C. O. E. "Energy metabolism in the developing larval stages of Ancylostoma tubaeforme and Haemonchus contortus: glycolytic and tncarboxylic acid cycle enzymes." Parasitology 90, no. 1 (February 1985): 169–77. http://dx.doi.org/10.1017/s0031182000049118.
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The activities of glycolytic and related enzymes and the tricarboxylic acid cycle enzymes were measured in freshly isolated 1st- (Li), 2nd- (L2) and 3rd-stage (L3) larvae of both Ancylostoma tubaeforme and Haemonchus contortus. All enzymes of the glycolytic pathway were present in all developmental stages of both strongylid nematodes although higher levels of activities were obtained in the pre-infective 1st- and 2nd-stage larvae than in the infective 3rd stage. However, the pre-infective larvae contained lower levels of pyruvate kinase (PK) than the infective larvae. Consequently, the pyruvate kinase to phosphoenolpyruvate carboxykinase (PEPCK) ratios were 0·23 and 0·26 for the L1s and L2s for A. tubaeforme and 0·36 and 0·21 for those of H. contortus respectively. High levels of activity of glucose-6-phosphate dehydrogenase obtained in the bacteriophagous pre-infective larvae were consistent with high rates of morphogenesis and substrate synthesis characteristic of the pre-infective stages. All the tricarboxylic acid cycle enzymes were present in the infective larvae of both nematodes while in the pre-infective Li and L2 stages, the enzymes at the beginning of the cycle, namely aconitate hydratase and NAD-linked isocitrate dehydrogenase, were not detected. A scheme was proposed for the energy metabolism of these developing larvae. In this scheme, the pre-infective larvae were shown to operate an anaerobic metabolic pathway involving the carboxylation of phosphoenolpyruvate (PEP) by phosphoenolpyru vate carboxykinase (PEPCK) to form oxaloacetate (OAA), whereas in the infective larvae the metabolic pathway favouring the direct dephosphorylation of PEP, as in vertebrate tissues, was followed.
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Tang, M. J., K. R. Suresh, and R. L. Tannen. "Carbohydrate metabolism by primary cultures of rabbit proximal tubules." American Journal of Physiology-Cell Physiology 256, no. 3 (March 1, 1989): C532—C539. http://dx.doi.org/10.1152/ajpcell.1989.256.3.c532.
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Renal proximal tubular epithelia were used to assess the factors responsible for the induction of glycolysis in cultured cells. Primary cultures of rabbit proximal tubules, which achieved confluency at 6 days, exhibited hormonal responsiveness and brush-border characteristics typical of proximal tubular cells. Beginning at day 4, these cultured cells exhibited increased glycolytic metabolism reflected by enhanced glucose uptake and lactate production, along with parallel increases in activity of the glycolytic enzymes, pyruvate kinase and lactate dehydrogenase. The gluconeogenic enzymes, phosphoenolpyruvate carboxykinase (PEPCK) and fructose-1,6-bisphosphatase (FDP), were downregulated, and the cultured cells exhibited lower oxygen consumption rates than fresh tubules. Cells grown on a rocker, to mitigate hypoxia, exhibited a metabolic and enzymatic profile similar to cells grown under still conditions. ATP levels in cultured cells were higher than in fresh tubules. Furthermore, pyruvate kinase activity was higher in cells grown in media containing 0.5 as contrasted with 25 mM glucose. The enhanced glycolytic metabolism exhibited by cultured proximal tubular cells appears to be a characteristic of proliferation and is not a response to hypoxia, the Pasteur effect, or environmental glucose.
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Dimou, Maria, Anca Paunescu, Georgios Aivalakis, Emmanouil Flemetakis, and Panagiotis Katinakis. "Co-localization of Carbonic Anhydrase and Phosphoenol-pyruvate Carboxylase and Localization of Pyruvate Kinase in Roots and Hypocotyls of Etiolated Glycine max Seedlings." International Journal of Molecular Sciences 10, no. 7 (June 29, 2009): 2896–910. http://dx.doi.org/10.3390/ijms10072896.
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Dougherty, Thomas M., and W. W. Cleland. "pH Studies on the chemical mechanism of rabbit muscle pyruvate kinase. 2. Physiological substrates and phosphoenol-.alpha.-ketobutyrate." Biochemistry 24, no. 21 (October 1985): 5875–80. http://dx.doi.org/10.1021/bi00342a028.
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He, Lina, Yang Li, Ni Zeng, and Bangyan L. Stiles. "Regulation of basal expression of hepatic PEPCK and G6Pase by AKT2." Biochemical Journal 477, no. 5 (March 13, 2020): 1021–31. http://dx.doi.org/10.1042/bcj20190570.
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Hepatic glucose metabolism signaling downstream of insulin can diverge to multiple pathways including AKT. Genetic studies suggest that AKT is necessary for insulin to suppress gluconeogenesis. To specifically address the role of AKT2, the dominant liver isoform of AKT in the regulation of gluconeogenesis genes, we generated hepatocytes lacking AKT2 (Akt2−/−). We found that, in the absence of insulin signal, AKT2 is required for maintaining the basal level expression of phosphoenolpyruvate carboxyl kinase (PEPCK) and to a lesser extent G6Pase, two key rate-limiting enzymes for gluconeogenesis that support glucose excursion due to pyruvate loading. We further showed that this function of AKT2 is mediated by the phosphorylation of cyclic AMP response element binding (CREB). Phosphorylation of CREB by AKT2 is needed for CREB to induce the expression of PEPCK and likely represents a priming event for unstimulated cells to poise to receive glucagon and other signals. The inhibition of gluconeogenesis by insulin is also dependent on the reduced FOXO1 transcriptional activity at the promoter of PEPCK. When insulin signal is absent, this activity appears to be inhibited by AKT2 in manner that is independent of its phosphorylation by AKT. Together, this action of AKT2 on FOXO1 and CREB to maintain basal gluconeogenesis activity may provide fine-tuning for insulin and glucocorticoid/glucagon to regulate gluconeogenesis in a timely manner to meet metabolic needs.
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Wang, Liu, Yanlin Guo, Mingzhu Pan, Xinxin Li, Dong Huang, Yue Liu, Chenglong Wu, Wenbing Zhang, and Kangsen Mai. "Functions of Forkhead Box O on Glucose Metabolism in Abalone Haliotis discus hannai and Its Responses to High Levels of Dietary Lipid." Genes 12, no. 2 (February 20, 2021): 297. http://dx.doi.org/10.3390/genes12020297.
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The forkhead box O (FoxO) subfamily is a member of the forkhead transcription factor family. It has regulation functions in glucose metabolism in mammals and fish. In the present study, a gene of the foxo homolog in abalone Haliotis discus hannai was cloned. A conservative forkhead (FH) domain and a transactivation (FoxO-TAD) domain were identified. Abalone foxo-specific siRNA (small interfering RNA) was injected to investigate the functions of foxo on glucose metabolism. Knockdown of foxo inhibited expression of phosphoenolpyruvate carboxykinase (pepck) and significantly increased expressions of hexokinase (hk) and pyruvate kinase (pk), but it failed to inhibit the relative mRNA level of glucose-6-phosphatase (g6pase). Then, a 100-day feeding trial was conducted to investigate the response of foxo and glucose metabolism in abalone fed with 1.57% (LFD, low-fat diet), 3.82% (MFD, middle-fat diet) and 6.72% (HFD, high-fat diet) of dietary lipid, respectively. The insulin-signaling pathway (AKT) was depressed and FoxO was activated by the HFD, but it did not inhibit glycolysis (hk) or improved gluconeogenesis significantly (pepck and g6pase). At the same time, impaired hepatopancreas glycogen storage raised hemolymph glucose levels. In conclusion, abalone foxo can be regulated by dietary lipid and can regulate gluconeogenesis or glycolysis in response to changes of dietary lipid levels, in which glycogen metabolism plays an important role.
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Qiu, Ting, Jia-Xue Shi, Chao Cheng, Hong Jiang, Hai-Nan Ruan, Jun Li, and Chan-Min Liu. "Avicularin Attenuates Lead-Induced Impairment of Hepatic Glucose Metabolism by Inhibiting the ER Stress-Mediated Inflammatory Pathway." Nutrients 14, no. 22 (November 13, 2022): 4806. http://dx.doi.org/10.3390/nu14224806.
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Lead (Pb), an environmental hazard, causes several human diseases. Avicularin (Avi), a main dietary flavonoid found in several plants and fruits, exhibits potential protective properties on organs. However, the molecular mechanisms of Avi’s protective effects against Pb-induced damage are not clear. In our study, the effects of Avi on Pb-induced hepatotoxicity were evaluated using ICR mice. We have revealed for the first time that treatment with Avi significantly reduced hepatic inflammation, endoplasmic reticulum stress (ERS) and glucose metabolism disorder induced by Pb. Avi decreased the serum biochemical indicators of glucose metabolism. Avi increased the activities of glycogenolysis rate-limiting enzyme hexokinase (HK), pyruvate kinase (PK), glucokinase (GK) and glycogen phosphorylase (PYG) and inhibited the activities of gluconeogenesis rate-limiting enzyme phosphoenolpyruvate carboxy kinase (PEPCK) and glucose-6-phosphate dehydrogenase (G6PD). Avi decreased the protein expression levels of glucose-regulated protein 78 (GRP78), phosphorylated inositol requiring enzyme 1 (p-IRE1), phosphorylated RNA-dependent protein kinase-like ER kinase (p-PERK) and phosphorylated eukaryotic initiation factor 2α (p-eIF2α). The levels of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) were decreased in the liver as a result of Avi suppression Pb-induced inflammation. These results indicated that Avi attenuated Pb-induced impairment of hepatic glucose metabolism by the ERS and inflammation pathway.
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Kloprogge, E., and J. W. Akkerman. "Platelet-activating factor (PAF-acether) induces high- and low-affinity binding of fibrinogen to human platelets via independent mechanisms." Biochemical Journal 240, no. 2 (December 1, 1986): 403–12. http://dx.doi.org/10.1042/bj2400403.
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When human platelets are incubated with 500 nM-PAF-acether (platelet-activating factor. 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) under equilibrium conditions (60 min, 22 degrees C, non-stirred suspensions), two classes of fibrinogen binding sites are exposed: one class with a high affinity [Kd (7.2 +/- 2.1) X 10(-8) M, 2367 +/- 485 sites/platelet, n = 9] and one class with a low affinity [Kd (5.9 +/- 2.4) X 10(-7) M, 26972 +/- 8267 sites/platelet]. Preincubation with inhibitors of cyclo-oxygenase (acetylsalicylic acid, indomethacin) or thromboxane synthetase (UK 38.485) completely abolishes high-affinity binding, leaving low-affinity binding unchanged. In contrast, ADP scavengers (phosphocreatine/creatine kinase or phosphoenol pyruvate/pyruvate kinase) completely prevent low-affinity binding, leaving high-affinity binding unaltered. Initial binding studies (2-10 min incubation) confirm these findings with a major part of the binding being sensitive to ADP scavengers, a minor part sensitive to indomethacin and complete blockade with both inhibitors. Increasing the temperature to 37 degrees C decreases the number of low affinity-binding sites 6-fold without changing high-affinity binding. Aggregation, measured as the rate of single platelet disappearance, then depends on high-affinity binding at 10 nM-fibrinogen or less, whereas at 100 nM-fibrinogen or more low-affinity binding becomes predominant. These findings point at considerable platelet activation during binding experiments. However, arachidonate metabolism [(3H]arachidonate mobilization and thromboxane synthesis) and secretion [(14C]serotonin and beta-thromboglobulin) are about 10% or less of the amounts found under optimal conditions (5 units of thrombin/ml 37 degrees C, stirring). We conclude that PAF-acether induces little platelet activation under binding conditions. The amounts of thromboxane A2 and secreted ADP, however, are sufficient for initiating high- and low-affinity fibrinogen binding via mutually independent mechanisms.
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El Meligy, Salwa, Manal El Batch, and Ghada Abd El Alem. "Effect of Resveratrol on Dipeptidyl Peptidase-4 (DPP-4) and Phospho Enol Pyruvate Carboxy Kinase (PEPCK) in Streptozotocin -Induced Diabetic Rats." Bulletin of Egyptian Society for Physiological Sciences 31, no. 1 (December 1, 2011): 1–14. http://dx.doi.org/10.21608/besps.2011.35949.
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Salvarrey, M. S., J. J. B. Cannata, and J. J. Cazzulo. "Phosphoenolpyruvate carboxykinase from the moderate halophile Vibrio costicola. Purification, physicochemical properties and the effect of univalent-cation salts." Biochemical Journal 260, no. 1 (May 15, 1989): 221–30. http://dx.doi.org/10.1042/bj2600221.
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Phosphoenolpyruvate carboxykinase (PEPCK) was purified to homogeneity from the moderately halophilic bacterium Vibrio costicola. The enzyme is monomeric, with an Mr of 62,000, as determined by the Svedberg equation, by using values of s0(20,w) 4.4 x 10(-13) s, D20,w 6.13 x 10(-7) cm2.s-1 and v 0.719 cm3.g-1. Compared with other, non-halophilic, PEPCKs, the enzyme from V. costicola had a significantly lower total content of hydrophobic amino acids. The contents of glycine and serine were higher in the V. costicola enzyme (16.7 and 10.22% respectively) than in the non-halophilic PEPCKs (6.8-9.6% and 4.67-6.28% respectively). These results resemble those obtained by De Médicis & Rossignol [(1979) Experientia 35, 1546-1547] with the pyruvate kinase from V. costicola, and agree with the proposal by Lanyi [(1974) Bacteriol. Rev. 38, 272-290] of partial replacement of hydrophobic amino acids by glycine and serine to maintain the balance between hydrophobic and hydrophilic forces in halophilic enzymes. In agreement with this ‘halophilic’ characteristic, the PEPCK was somewhat stabilized by 1 M-KCl or -NaCl and by 20% (v/v) glycerol, and its oxaloacetate-decarboxylation and 14CO2-oxaloacetate-exchange reactions were activated by KCl and NaCl up to 1 M, whereas the fixation of CO2 on PEP had a maximum at 0.025-0.05 M salt. These facts suggest that the salts, at concentrations probably physiological for the bacterium, increase the formation of the complex of oxaloacetate and ATP with the enzyme, and the liberation of the products, PEP and ADP, thus favouring PEP synthesis.
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Kola, Blerina, Mirjam Christ-Crain, Francesca Lolli, Giorgio Arnaldi, Gilberta Giacchetti, Marco Boscaro, Ashley B. Grossman, and Márta Korbonits. "Changes in Adenosine 5′-Monophosphate-Activated Protein Kinase as a Mechanism of Visceral Obesity in Cushing’s Syndrome." Journal of Clinical Endocrinology & Metabolism 93, no. 12 (December 1, 2008): 4969–73. http://dx.doi.org/10.1210/jc.2008-1297.
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Objective: Features of the metabolic syndrome such as central obesity with insulin resistance and dyslipidemia are typical signs of Cushing’s syndrome and common side effects of prolonged glucocorticoid treatment. AMP-activated protein kinase (AMPK), a key regulatory enzyme of lipid and carbohydrate metabolism as well as appetite, is involved in the development of the deleterious metabolic effects of excess glucocorticoids, but no data are available in humans. In the current study, we demonstrate the effect of high glucocorticoid levels on AMPK activity of human adipose tissue samples from patients with Cushing’s syndrome. Methods: AMPK activity and mRNA expression of genes involved in lipid metabolism were assessed in visceral adipose tissue removed at abdominal surgery of 11 patients with Cushing’s syndrome, nine sex-, age-, and weight-matched patients with adrenal incidentalomas, and in visceral adipose tissue from four patients with non-endocrine-related abdominal surgery. Results: The patients with Cushing’s syndrome exhibited a 70% lower AMPK activity in visceral adipose tissue as compared with both incidentalomas and control patients (P = 0.007 and P < 0.001, respectively). Downstream targets of AMPK fatty acid synthase and phosphoenol-pyruvate carboxykinase were up-regulated in patients with Cushing’s syndrome. AMPK activity was inversely correlated with 0900 h serum cortisol and with urinary free cortisol. Conclusions: Our data suggest that glucocorticoids inhibit AMPK activity in adipose tissue, suggesting a novel mechanism to explain the deposition of visceral adipose tissue and the consequent central obesity observed in patients with iatrogenic or endogenous Cushing’s syndrome.
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Su, Chengfu, Chuanbin Yang, Man Gong, Yingying Ke, Peipei Yuan, Xiaolan Wang, Min Li, Xiaoke Zheng, and Weisheng Feng. "Antidiabetic Activity and Potential Mechanism of Amentoflavone in Diabetic Mice." Molecules 24, no. 11 (June 11, 2019): 2184. http://dx.doi.org/10.3390/molecules24112184.
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Aim: To investigate the anti-diabetic activity of amentoflavone (AME) in diabetic mice, and to explore the potential mechanisms. Methods: Diabetic mice induced by high fat diet and streptozotocin were administered with amentoflavone for 8 weeks. Biochemical indexes were tested to evaluate its anti-diabetic effect. Hepatic steatosis, the histopathology change of the pancreas was evaluated. The activity of glucose metabolic enzymes, the expression of Akt and pAkt, and the glucose transporter type 4 (GLUT4) immunoreactivity were detected. Results: AME decreased the level of glucose, total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C) and glucagon, and increased the levels of high density lipoprotein cholesterol (HDL-C) and insulin. Additionally, AME increased the activity of glucokinase (GCK), phosphofructokinase-1 (PFK-1), and pyruvate kinase (PK), and inhibited the activity of glycogen synthase kinase-3 (GSK-3), phosphoenolpyruvate carboxykinase (PEPCK), and glucose-6-phosphatase (G-6-Pase). Mechanistically, AME increased superoxide dismutase (SOD), decreased malondialdehyde (MDA), activation of several key signaling molecules including pAkt (Ser473), and increased the translocation to the sedimenting membranes of GLUT4 in skeletal muscle tissue. Conclusions: AME exerted anti-diabetic effects by regulating glucose and lipid metabolism, perhaps via anti-oxidant effects and activating the PI3K/Akt pathway. Our study provided novel insight into the role and underlying mechanisms of AME in diabetes.
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Reifel-Miller, Anne, Keith Otto, Eric Hawkins, Robert Barr, William R. Bensch, Chris Bull, Sharon Dana, et al. "A Peroxisome Proliferator-Activated Receptor α/γ Dual Agonist with a Unique in Vitro Profile and Potent Glucose and Lipid Effects in Rodent Models of Type 2 Diabetes and Dyslipidemia." Molecular Endocrinology 19, no. 6 (June 1, 2005): 1593–605. http://dx.doi.org/10.1210/me.2005-0015.
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Abstract LSN862 is a novel peroxisome proliferator-activated receptor (PPAR)α/γ dual agonist with a unique in vitro profile that shows improvements on glucose and lipid levels in rodent models of type 2 diabetes and dyslipidemia. Data from in vitro binding, cotransfection, and cofactor recruitment assays characterize LSN862 as a high-affinity PPARγ partial agonist with relatively less but significant PPARα agonist activity. Using these same assays, rosiglitazone was characterized as a high-affinity PPARγ full agonist with no PPARα activity. When administered to Zucker diabetic fatty rats, LSN862 displayed significant glucose and triglyceride lowering and a significantly greater increase in adiponectin levels compared with rosiglitazone. Expression of genes involved in metabolic pathways in the liver and in two fat depots from compound-treated Zucker diabetic fatty rats was evaluated. Only LSN862 significantly elevated mRNA levels of pyruvate dehydrogenase kinase isozyme 4 and bifunctional enzyme in the liver and lipoprotein lipase in both fat depots. In contrast, both LSN862 and rosiglitazone decreased phosphoenol pyruvate carboxykinase in the liver and increased malic enzyme mRNA levels in the fat. In addition, LSN862 was examined in a second rodent model of type 2 diabetes, db/db mice. In this study, LSN862 demonstrated statistically better antidiabetic efficacy compared with rosiglitazone with an equivalent side effect profile. LSN862, rosiglitazone, and fenofibrate were each evaluated in the humanized apoA1 transgenic mouse. At the highest dose administered, LSN862 and fenofibrate reduced very low-density lipoprotein cholesterol, whereas, rosiglitazone increased very low-density lipoprotein cholesterol. LSN862, fenofibrate, and rosiglitazone produced maximal increases in high-density lipoprotein cholesterol of 65, 54, and 30%, respectively. These findings show that PPARγ full agonist activity is not necessary to achieve potent and efficacious insulin-sensitizing benefits and demonstrate the therapeutic advantages of a PPARα/γ dual agonist.
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Segura, Daniel, and Guadalupe Espín. "Mutational Inactivation of a Gene Homologous to Escherichia coli ptsP Affects Poly-β-Hydroxybutyrate Accumulation and Nitrogen Fixation in Azotobacter vinelandii." Journal of Bacteriology 180, no. 18 (September 15, 1998): 4790–98. http://dx.doi.org/10.1128/jb.180.18.4790-4798.1998.
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ABSTRACT Strain DS988, an Azotobacter vinelandii mutant with a reduced capacity to accumulate poly-β-hydroxybutyrate, was isolated after mini-Tn5 mutagenesis of the UW136 strain. Cloning and nucleotide sequencing of the affected locus revealed a gene homologous to Escherichia coli ptsP which encodes enzyme INtr, a homologue of enzyme I of the phosphoenol pyruvate-sugar phosphotransferase system with an N-terminal domain similar to the N-terminal domain of some NifA proteins. Strain DS988 was unable to grow diazotrophically with 10 mM glucose as a carbon source. Diazotrophic growth on alternative carbon sources such as gluconate was only slightly affected. Glucose uptake, as well as glucose kinase and glucose-6-phosphate-dehydrogenase activities that lead to the synthesis of gluconate-6-phosphate, were not affected by the ptsP mutation. The inability of DS988 to grow diazotrophically in 10 mM glucose was overcome by supplying ammonium or other sources of fixed nitrogen. Acetylene reduction activity but not transcription of the nitrogenase structural gene nifH was shown to be impaired in strain DS988 when it was incubated in 10 mM glucose. The diazotrophic growth defect of DS988 was restored either by increasing the glucose concentration to above 20 mM or by lowering the oxygen concentration. These data suggest that a mutation inptsP leads to a failure in poly-β-hydroxybutyrate metabolism and in the respiratory protection of nitrogenase under carbon-limiting conditions.
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Zhao, Shuo, Daniel Garcia, Yinglei Zhao, and Danfeng Huang. "Hydro-Electro Hybrid Priming Promotes Carrot (Daucus carota L.) Seed Germination by Activating Lipid Utilization and Respiratory Metabolism." International Journal of Molecular Sciences 22, no. 20 (October 14, 2021): 11090. http://dx.doi.org/10.3390/ijms222011090.
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Carrot (Daucus carota L.) is widely cultivated as one of the most important root crops, and developing an effective presowing treatment method can promote the development of modern mechanized precision sowing. In the present study, a novel seed priming technology, named hydro-electro hybrid priming (HEHP), was used to promote the germination of carrot seeds. Seed germination experiments showed that HEHP was able to increase the germination index (GI) and vigor index (VI) by 3.1-fold and 6.8-fold, respectively, and the effect was significantly superior to that of hydro-priming (HYD) and electrostatic field treatment (EF). The consumption and utilization rate of seed storage reserves were also greatly improved. Meanwhile, both glyoxysomes and mitochondria were found to appear ahead of time in the endosperm cells of HEHP through observations of the subcellular structure of the endosperm. Activities of isocitrate lyase (ICL), NAD-dependent malate dehydrogenase (MDH), pyruvate kinase (PK), and alcohol dehydrogenase (ADH) were significantly increased by HEHP. From transcriptome results, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to the glyoxylate cycle, glycolysis, gluconeogenesis, and the citrate cycle were significantly enriched and real-time quantitative PCR (qRT-PCR) analysis confirmed the expression pattern of 15 critical differentially expressed genes (DEGs) in these pathways. All DEGs encoding MDH, phosphoenolpyruvate carboxykinase (PEPCK), and PK were upregulated in HEHP; thus, it is reasonable to infer that the transformation of malate, oxalacetate, phosphoenolpyruvate, and pyruvate in the cytoplasm may be pivotal for the energy supply during early germination. The results suggest that the optimal effect of HEHP is achieved by initiating stored lipid utilization and respiratory metabolism pathways related to germination.
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Wagner, William R., and Jeffrey A. Hubbell. "ADP Receptor Antagonists and Converting Enzyme Systems Reduce Platelet Deposition onto Collagen." Thrombosis and Haemostasis 67, no. 04 (1992): 461–67. http://dx.doi.org/10.1055/s-0038-1648471.
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SummaryThe effect of the ADP receptor antagonists ATP and adenosine 5’-(β, γ-methylene)triphosphate (AMP-PCP), and the ADP-utilizing enzyme systems creatine phosphokinase/creatine phosphate (CPK/CP) and pyruvate kinase/phosphoenol pyruvate (PK/PEP) on platelet deposition onto type I collagen was examined. An in vitro perfusion system was used, which allowed continuous visualization of the deposition of fluorescently labelled platelets. This system also provided well-controlled rheology, precise quantification of deposition, and allowed the use of heparinized whole human blood (3 u/ml). Heparinization at this level permits the local generation of thrombin near surface platelet aggregates. The contribution of ADP is thus studied with the combined effects of thrombin, thromboxane A2, and other aggregating agents present. Results from these studies indicate that ATP was capable of inhibiting deposition by 60% at 1 pM and 90% at 5 μM (whole blood cone.). AMP-PCP inhibited deposition in a dose dependent manner with a Ki of approximately 80 μM and a maximum inhibition of 60%. Inhibition by CPK/CP was measured at 20, 40, and 60 u/ml, with approximately 45% inhibition achieved for the latter two concentrations. PK/ PEP at 60 u/ml resulted in 70% inhibition. These results support a role for ADP in mediating platelet recruitment in thrombus growth on collagen. Previous work utilizing animal bleeding times supports this conclusion; the present study demonstrates that this role is not dependent upon endothelial or vasoconstrictive effects. Intraplatelet cAMP levels were raised with respect to controls upon exposure to ATP at 8.3 μM (p <0.025), and 15 μM (p <0.005), as well as AMP-PCP at 42-500 μM (p <0.005). Since increasing intraplatelet cAMP may affect platelet function, these results raise another possible interpretation for some of our platelet deposition data as well as that of previous experimenters. However, since ATP at 1 μM was not shown to affect intraplatelet cAMP, it is believed that at least part of the ATP-mediated inhibition was due to ADP receptor competition.
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Haukeland, John Willy, Tuva B. Dahl, Arne Yndestad, Ivar P. Gladhaug, Else Marit Løberg, Terese Haaland, Zbigniew Konopski, et al. "Fetuin A in nonalcoholic fatty liver disease: in vivo and in vitro studies." European Journal of Endocrinology 166, no. 3 (March 2012): 503–10. http://dx.doi.org/10.1530/eje-11-0864.
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ObjectiveFetuin A has been associated with insulin resistance and the metabolic syndrome. We therefore explored the role of fetuin A in nonalcoholic fatty liver disease (NAFLD).DesignCross-sectional and intervention studies.MethodsWe included 111 subjects with histologically proven NAFLD of whom 44 participated in a randomized, controlled trial with metformin. One hundred and thirty-one healthy subjects and 13 subjects undergoing hepatic surgery for metastatic cancer served as controls. Main outcome variables were circulating levels of fetuin A according to the presence of NAFLD, hepatic gene expression of fetuin A and key enzymes in glucose and lipid metabolism, and the effect of metformin on fetuin A levels in vivo and in vitro (HepG2 cells).ResultsFetuin A levels were significantly higher in NAFLD patients compared with controls (324±98 vs 225±75 mg/l, P<0.001). NAFLD was a significant predictor of elevated fetuin A levels (β=174 (95% confidence interval: 110–234)) independent of body mass index, age, sex, fasting glucose, and triglycerides. Hepatic fetuin A mRNA levels correlated significantly with hepatic mRNA levels of key enzymes in lipid (sterol regulatory element-binding protein 1c, carnitine palmitoyltransferase 1) and glucose (phosphoenol pyruvate kinase 1, glucose-6-phosphatase) metabolism. Plasma fetuin A levels decreased significantly after metformin treatment compared with placebo (−40±47 vs 15±82 mg/l, P=0.008). Metformin induced a dose-dependent decrease in fetuin A secretion in vitro.ConclusionsFetuin A levels were elevated in NAFLD. Hepatic expression of fetuin A correlated with key enzymes in glucose and lipid metabolism. Metformin decreased fetuin A levels in vitro.
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Shih, Chun-Ching, Cheng-Hsiu Lin, Yih-Jiun Lin, and Jin-Bin Wu. "Validation of the Antidiabetic and Hypolipidemic Effects of Hawthorn by Assessment of Gluconeogenesis and Lipogenesis Related Genes and AMP-Activated Protein Kinase Phosphorylation." Evidence-Based Complementary and Alternative Medicine 2013 (2013): 1–12. http://dx.doi.org/10.1155/2013/597067.
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Since with the increased use of antidiabetic and antihyperlipidemic effect of phytonutrients for daily supplement has gained considerable attention worldwide, we examine the effect and molecular mechanism ofCrataegus pinnatifidaBge. var.majorN.E. Br. (hawthorn) by quantifying the expression of hepatic gluconeogenesis and lipogenesis on diabetes and dyslipidemia in high-fat (HF)-fed C57BL/6J mice. Firstly, mice were divided randomly into two groups: the control (CON) group was fed with a low-fat diet, whereas the experimental group was fed a 45% HF diet for 8 weeks. Afterwards, the CON group was treated with vehicle, whereas the HF group was subdivided into five groups and was given orally hawthorn extract (including 0.2, 0.5, 1.0 g/kg/day extracts) or rosiglitazone (Rosi) or vehicle for 4 weeks afterward. Diabetic mice showed an increase in plasma glucose and insulin. Glucose lowering was comparable with Rosi-treated mice. This study demonstrated that hawthorn was effective in ameliorating the HF diet-induced hyperglycemia, hypertriglyceridemia and hypercholesterolaemia. Hawthorn extract significantly increases the hepatic protein contents of AMP-activated protein kinase (AMPK) phosphorylation and reduces expression of phosphenol pyruvate carboxykinase (PEPCK) and glucose production. Furthermore, hawthorn decreased in hepatic triacylglycerol and cholesterol synthesis (including sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), SREBP2). An increase in expressions of apoA-I gene and high-density lipoprotein cholesterol (HDL-C) was detected in HF-fed mice treated with high dose hawthorn. Our data suggest that hawthorn extract are capable of decreasing glucose production and triacylglycerol synthesis by inducing AMPK-phosphorylation and hawthorn is a candidate source of antidiabetic and antihyperlipidemic phytonutrients factors.
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Reul, BA, DJ Becker, LN Ongemba, CJ Bailey, JC Henquin, and SM Brichard. "Improvement of glucose homeostasis and hepatic insulin resistance in ob/ob mice given oral molybdate." Journal of Endocrinology 155, no. 1 (October 1, 1997): 55–64. http://dx.doi.org/10.1677/joe.0.1550055.
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Molybdate (Mo) exerts insulinomimetic effects in vitro. In this study, we evaluated whether Mo can improve glucose homeostasis in genetically obese, insulin-resistant ob/ob mice. Oral administration of Mo (174 mg/kg molybdenum element) for 7 weeks did not affect body weight, but decreased the hyperglycaemia (approximately 20 mM) of obese mice to the levels of lean (L) (+/+) mice, and reduced the hyperinsulinaemia to one-sixth of pretreatment levels. Tolerance to oral glucose was improved: total glucose area was 30% lower in Mo-treated mice than in untreated ob/ob mice (O), while the total insulin area was halved. Hepatic glucokinase (GK) mRNA level and activity were unchanged in O mice compared with L mice, but the mRNA level and activity of L-type pyruvate kinase (L-PK) were increased in O mice by 3.5- and 1.7-fold respectively. Mo treatment increased GK mRNA levels and activity (by approximately 2.2-fold and 61% compared with O values), and had no, or only a mild, effect on the already increased L-PK variables. mRNA levels and activity of the gluconeogenic enzyme, phosphoenolpyruvate carboxykinase (PEPCK) were augmented in O liver (sixfold and by 57% respectively), and these were reduced by Mo treatment. Insulin binding to partially purified receptors from liver was reduced in O mice and restored by Mo treatment. Despite this correction, overall receptor tyrosine kinase activity was not improved in Mo mice. Moreover, the overexpression (by two- to fourfold) of the cytokine tumour necrosis factor alpha (TNF alpha) in white adipose tissue, which may have a determinant role in the insulin resistance of the O mice, was unaffected by Mo. Likewise, overexpression of the ob gene in white adipose tissue was unchanged by Mo. In conclusion, Mo markedly improved glucose homeostasis in the ob/ob mice by an insulin-like action which appeared to be exerted distal to the insulin receptor tyrosine kinase step. The blood glucose-lowering effect of Mo was unrelated to over-expression of the TNF alpha and ob genes in O mice, but resulted at least in part from attenuation of liver insulin resistance by the reversal of pre-translational regulatory defects in these mice.
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Liu, Hongyu, Ling Pan, Jianfei Shen, Beiping Tan, Xiaohui Dong, Qihui Yang, Shuyan Chi, and Shuang Zhang. "Effects of Carbohydrase Supplementation on Growth Performance, Intestinal Digestive Enzymes and Flora, Glucose Metabolism Enzymes, and glut2 Gene Expression of Hybrid Grouper (Epinephelus fuscoguttatus♀ × E. lanceolatus♂) Fed Different CHO/L Ratio Diets." Metabolites 13, no. 1 (January 7, 2023): 98. http://dx.doi.org/10.3390/metabo13010098.
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An optimal carbohydrate-to-lipid (CHO: L) ratio facilitates fish growth and protein conservation, and carbohydrase promotes nutrient absorption. Therefore, an 8-week feeding trial was conducted to investigate the effects of carbohydrase supplementation on growth performance, intestinal digestive enzymes and flora, glucose metabolism enzymes and glut2 gene expression in juvenile hybrid grouper (Epinephelus fuscoguttatus♀× Epinephelus lanceolatus♂) fed different CHO: L ratios diets. L, M, and H represent CHO:L ratios of 0.91, 1.92 and 3.91, respectively. LE, ME, and HE represent CHO:L ratios of 0.91, 1.92, 3.91, respectively, supplemented with the same ratio of carbohydrase. Results showed that weight gain rate (WGR) and specific growth rate (SGR) reached a maximum in group M and were significantly enhanced by carbohydrase (p < 0.05). Crude lipid content decreased significantly with an increase in the dietary CHO:L ratio (p < 0.05). Significant increases in the trypsin (TRY) and amylase (AMS) activities and significant decreases in the lipase (LPS) activity were observed with increasing dietary CHO:L ratio, and the former two were significantly promoted by carbohydrase (p < 0.05). The content of liver and muscle glycogen increased significantly with the increasing dietary CHO:L ratio but decreased significantly after carbohydrase supplementation (p < 0.05). The glucokinase (GK), pyruvate kinase (PK), Phosphate 6 fructokinase-1 (PFK-1) and phosphoenolpyruvate kinase (PEPCK) activities increased significantly with increasing dietary CHO:L ratio (p < 0.05). Glut2 mRNA expression decreased significantly in liver and increased significantly in intestine with increasing dietary CHO:L ratio (p < 0.05). By linear discriminant analysis (LDA), the abundance of Alistipe was significantly higher in Group ME than in Group M. These results suggested that hybrid grouper can only moderately utilize dietary carbohydrate and lipid in diet, and a certain amount of high glycemic lipids occurred when fed with high-carbohydrate diets. By the weight gain for basis, the supplementation of carbohydrase in Group H with amylase, glycosylase, and pullulanase in a 1:1:1 ratio effectively lowered glycemic lipids, promoted the growth of grouper, digestive enzymes activities and carbohydrate metabolic enzyme, and glut2 gene expression in intestine, effectively balancing the negative effects of high-carbohydrate diet and improving the utilization of carbohydrate.
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Cui, Xiang, Da-Wei Qian, Shu Jiang, Er-Xin Shang, Zhen-Hua Zhu, and Jin-Ao Duan. "Scutellariae Radix and Coptidis Rhizoma Improve Glucose and Lipid Metabolism in T2DM Rats via Regulation of the Metabolic Profiling and MAPK/PI3K/Akt Signaling Pathway." International Journal of Molecular Sciences 19, no. 11 (November 18, 2018): 3634. http://dx.doi.org/10.3390/ijms19113634.
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Aim Scutellariae Radix (SR) and Coptidis Rhizoma (CR) have often been combined to cure type 2 diabetes mellitus (T2DM) in the clinical practice for over thousands of years, but their compatibility mechanism is not clear. Mitogen-activated protein kinase (MAPK) signaling pathway has been suggested to play a critical role during the process of inflammation, insulin resistance, and T2DM. This study was designed to investigate their compatibility effects on T2DM rats and explore the underlying mechanisms by analyzing the metabolic profiling and MAPK/PI3K/Akt signaling pathway. Methods The compatibility effects of SR and CR were evaluated with T2DM rats induced by a high-fat diet (HFD) along with a low dose of streptozocin (STZ). Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to discover potential biomarkers. The levels of pro-inflammatory cytokines; biochemical indexes in serum, and the activities of key enzymes related to glycometabolism in liver were assessed by ELISA kits. qPCR was applied to examine mRNA levels of key targets in MAPK and insulin signaling pathways. Protein expressions of p65; p-p65; phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K); phosphorylated-PI3K (p-PI3K); protein kinase B (Akt); phosphorylated Akt (p-Akt) and glucose transporter 2 (Glut2) in liver were investigated by Western blot analysis. Results Remarkably, hyperglycaemia, dyslipidemia, inflammation, and insulin resistance in T2DM were ameliorated after oral administration of SR and CR, particularly their combined extracts. The effects of SR, CR, low dose of combined extracts (LSC) and high dose of combined extracts (HSC) on pro-inflammatory cytokine transcription in T2DM rats showed that the MAPK pathway might account for the phenomenon with down-regulation of MAPK (P38 mitogen-activated protein kinases (P38), extracellular regulated protein kinases (ERK), and c-Jun N-terminal kinase (JNK)) mRNA, and protein reduction in p-P65. While mRNA levels of key targets such as insulin receptor substrate 1 (IRS1), PI3K, Akt2, and Glut2 in the insulin signaling pathway were notably up-modulated, phosphorylations of PI3K, Akt, and expression of Glut2 were markedly enhanced. Moreover, the increased activities of phosphoenolpyruvate carboxykinase (PEPCK), fructose-1,6-bisphosphatase (FBPase), glucose 6-phosphatase (G6Pase), and glycogen phosphorylase (GP) were highly reduced and the decreased activities of glucokinase (GK), phosphofructokinase (PFK), pyruvate kinase (PK), and glycogen synthase (GS) in liver were notably increased after treatment. Further investigation indicated that the metabolic profiles of plasma and urine were clearly improved in T2DM rats. Fourteen potential biomarkers (nine in plasma and five in urine) were identified. After intervention, these biomarkers returned to normal level to some extent. Conclusion The results showed that SR, CR, and combined extract groups were normalized. The effects of combined extracts were more remarkable than single herb treatment. Additionally, this study also showed that the metabonomics method is a promising tool to unravel how traditional Chinese medicines work.
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Zhang, Xiangsheng, Chaokai Huang, Yuhang Yang, Xiangkai Li, Chen Guo, Zheng Yang, Shichao Xie, et al. "Dietary Corn Starch Levels Regulated Insulin-Mediated Glycemic Responses and Glucose Homeostasis in Swimming Crab (Portunus trituberculatus)." Aquaculture Nutrition 2022 (September 6, 2022): 1–15. http://dx.doi.org/10.1155/2022/2355274.
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Carbohydrate is the cheapest source of energy among the three major nutrient groups, an appropriate amount of carbohydrates can reduce feed cost and improve growth performance, but carnivorous aquatic animals cannot effectively utilize carbohydrates. The objectives of the present study are aimed at exploring the effects of dietary corn starch levels on glucose loading capacity, insulin-mediated glycemic responses, and glucose homeostasis for Portunus trituberculatus. After two weeks of feeding trial, swimming crabs were starved and sampled at 0, 1, 2, 3, 4, 5, 6, 12, and 24 hours, respectively. The results indicated that crabs fed diet with 0% corn starch exhibited lower glucose concentration in hemolymph than those fed with the other diets, and glucose concentration in hemolymph remained low with the extension of sampling time. The glucose concentration in hemolymph of crabs fed with 6% and 12% corn starch diets reached the peak after 2 hours of feeding; however, the glucose concentration in hemolymph of crabs fed with 24% corn starch attained the highest value after 3 hours of feeding, and the hyperglycemia lasted for 3 hours and decreased rapidly after 6 hours of feeding. Enzyme activities in hemolymph related to glucose metabolism such as pyruvate kinase (PK), glucokinase (GK), and phosphoenolpyruvate carboxykinase (PEPCK) were significantly influenced by dietary corn starch levels and sampling time. Glycogen content in hepatopancreas of crabs fed with 6% and 12% corn starch first increased and then decreased; however, the glycogen content in hepatopancreas of crabs fed with 24% corn starch significantly increased with the prolongation of feeding time. In the 24% corn starch diet, insulin-like peptide (ILP) in hemolymph reached a peak after 1 hour of feeding and then significantly decreased, whereas crustacean hyperglycemia hormone (CHH) was not significantly influenced by dietary corn starch levels and sampling time. ATP content in hepatopancreas peaked at 1 h after feeding and then decreased significantly in different corn starch feeding groups, while the opposite trend was observed in NADH. The activities of mitochondrial respiratory chain complexes I, II, III, and V of crabs fed with different corn starch diets significantly increased first and then decreased. In addition, relative expressions of genes related to glycolysis, gluconeogenesis, glucose transport, glycogen synthesis, insulin signaling pathway, and energy metabolism were significantly affected by dietary corn starch levels and sampling time. In conclusion, the results of the present study reveal glucose metabolic responses were regulated by different corn starch levels at different time points and play an important role in clearing glucose through increased activity of insulin, glycolysis, and glycogenesis, along with gluconeogenesis suppression.
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Fulgencio, Jean-Pierre, Claude Kohl, Jean Girard, and Jean-Paul Pégorier. "Effect of metformin on fatty acid and glucose metabolism in freshly isolated hepatocytes and on specific gene expression in cultured hepatocytes11Abbreviations: CPT I or II, carnitine palmitoyltransferase I or II; mtHMG-CoA synthase, mitochondrial hydroxymethylglutaryl-CoA synthase; Glc-6-Pase, glucose-6-phosphatase; PEPCK, phosphoenolpyruvate carboxykinase; GK, glucokinase; L-PK, liver-type pyruvate kinase; and ACS, acyl-CoA synthetase." Biochemical Pharmacology 62, no. 4 (August 2001): 439–46. http://dx.doi.org/10.1016/s0006-2952(01)00679-7.
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Seo, Hanjin, and Hyomin Lee. "Spatiotemporal control of signal-driven enzymatic reaction in artificial cell-like polymersomes." Nature Communications 13, no. 1 (September 2, 2022). http://dx.doi.org/10.1038/s41467-022-32889-7.
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AbstractLiving cells can spatiotemporally control biochemical reactions to dynamically assemble membraneless organelles and remodel cytoskeleton. Herein, we present a microfluidic approach to prepare semi-permeable polymersomes comprising of amphiphilic triblock copolymer to achieve external signal-driven complex coacervation as well as biophysical reconstitution of cytoskeleton within the polymersomes. We also show that the microfluidic synthesis of polymersomes enables precise control over size, efficient encapsulation of enzymes as well as regulation of substrates without the use of biopores. Moreover, we demonstrate that the resulting triblock copolymer-based membrane in polymersomes is size-selective, allowing phosphoenol pyruvate to readily diffuse through the membrane and induce enzymatic reaction and successive coacervation or actin polymerization in the presence of pyruvate kinase and adenosine diphosphate inside the polymersomes. We envision that the Pluronic-based polymersomes presented in this work will shed light in the design of in vitro enzymatic reactions in artificial cell-like vesicles.
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Chen, Junyu, Ruchira Mitra, Shengjie Zhang, Zhenqiang Zuo, Lin Lin, Dahe Zhao, Hua Xiang, and Jing Han. "Unusual Phosphoenolpyruvate (PEP) Synthetase-Like Protein Crucial to Enhancement of Polyhydroxyalkanoate Accumulation in Haloferax mediterranei Revealed by Dissection of PEP-Pyruvate Interconversion Mechanism." Applied and Environmental Microbiology 85, no. 19 (July 26, 2019). http://dx.doi.org/10.1128/aem.00984-19.
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ABSTRACT Phosphoenolpyruvate (PEP)/pyruvate interconversion is a major metabolic point in glycolysis and gluconeogenesis and is catalyzed by various sets of enzymes in different Archaea groups. In this study, we report the key enzymes that catalyze the anabolic and catabolic directions of the PEP/pyruvate interconversion in Haloferax mediterranei. The in silico analysis showed the presence of a potassium-dependent pyruvate kinase (PYKHm [HFX_0773]) and two phosphoenol pyruvate synthetase (PPS) candidates (PPSHm [HFX_0782] and a PPS homolog protein named PPS-like [HFX_2676]) in this strain. Expression of the pykHm gene and ppsHm was induced by glycerol and pyruvate, respectively; whereas the pps-like gene was not induced at all. Similarly, genetic analysis and enzyme activities of purified proteins showed that PYKHm catalyzed the conversion from PEP to pyruvate and that PPSHm catalyzed the reverse reaction, while PPS-like protein displayed no function in PEP/pyruvate interconversion. Interestingly, knockout of the pps-like gene led to a 70.46% increase in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) production. The transcriptome sequencing (RNA-Seq) and quantitative reverse transcription-PCR (qRT-PCR) results showed that many genes responsible for PHBV monomer supply and for PHBV synthesis were upregulated in a pps-like gene deletion strain and thereby improved PHBV accumulation. Additionally, our phylogenetic evidence suggested that PPS-like protein diverged from PPS enzyme and evolved as a distinct protein with novel function in haloarchaea. Our findings attempt to fill the gaps in central metabolism of Archaea by providing comprehensive information about key enzymes involved in the haloarchaeal PEP/pyruvate interconversion, and we also report a high-yielding PHBV strain with great future potentials. IMPORTANCE Archaea, the third domain of life, have evolved diversified metabolic pathways to cope with their extreme habitats. Phosphoenol pyruvate (PEP)/pyruvate interconversion during carbohydrate metabolism is one such important metabolic process that is highly differentiated among Archaea. However, this process is still uncharacterized in the haloarchaeal group. Haloferax mediterranei is a well-studied haloarchaeon that has the ability to produce polyhydroxyalkanoates (PHAs) under unbalanced nutritional conditions. In this study, we identified the key enzymes involved in this interconversion and discussed their differences with their counterparts from other members of the Archaea and Bacteria domains. Notably, we found a novel protein, phosphoenolpyruvate synthetase-like (PPS-like), which exhibited high homology to PPS enzyme. However, PPS-like protein has evolved some distinct sequence features and functions, and strikingly the corresponding gene deletion helped to enhance poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) synthesis significantly. Overall, we have filled the gap in knowledge about PEP/pyruvate interconversion in haloarchaea and reported an efficient strategy for improving PHBV production in H. mediterranei.
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Ji, Ke, Hualiang Liang, Mingchun Ren, Xianping Ge, Liangkun Pan, and Heng Yu. "Nutrient metabolism in the liver and muscle of juvenile blunt snout bream (Megalobrama amblycephala) in response to dietary methionine levels." Scientific Reports 11, no. 1 (December 2021). http://dx.doi.org/10.1038/s41598-021-03084-3.
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AbstractA 75-day rearing trial was designed to study the response of juvenile Megalobrama amblycephala to dietary methionine (Met) levels. Three practical diets with graded Met levels (0.40%, 0.84% and 1.28% dry matter) were prepared to feed the juvenile fish. The results showed that the 0.84% Met diet significantly improved the growth compared with 0.40% diets. Compared with 0.84% and 1.28% Met, 0.40% Met significantly increased the hepatic lipid content, while decreasing the muscular lipid and glycogen contents. 0.40% Met decreased the protein levels of phospho-Eukaryotic initiation factor 4E binding protein-1 (p-4e-bp1), 4e-bp1 and Ribosomal protein S6 kinase 1 in the liver, compared with 0.84% diet, while an increasing trend was observed in the muscle. Met supplementation tended to decrease and increase lipid synthesis in the liver and muscle, respectively, via changing mRNA levels of sterol regulatory element-binding protein 1, fatty acid synthetase and acetyl-CoA carboxylase. 1.28% dietary Met promoted fatty acid β-oxidation and lipolysis in both the liver and muscle by increasing carnitine palmitoyl transferase 1, peroxisome proliferator activated receptor alpha, lipoprotein lipase and lipase mRNA levels. Compared with 0.40% and 0.84% dietary Met, 1.28% Met enhanced the mRNA levels of hepatic gluconeogenesis related genes phosphoenolpyruvate carboxykinase (pepck), and glucose-6-phosphatase, and muscular glycolysis related genes phosphofructokinase (pfk), and pyruvate kinase (pk). The mRNA levels of hepatic pfk, pk and glucokinase were markedly downregulated by 1.28% Met compared with 0.84% level. Muscular pepck, glycogen synthase, and hepatic glucose transporters 2 mRNA levels were induced by 1.28% Met. Generally, deficient Met level decreased the growth of juvenile Megalobrama amblycephala, and the different nutrient metabolism responses to dietary Met were revealed in the liver and muscle.
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Luo, Meng-Juan, Ying Wang, Si-Yu Chen, and Ze-Min Yang. "Astragalus Polysaccharides Alleviate Type 2 Diabetic Rats by Reversing the Expressions of Sweet Taste Receptors and Genes Related to Glycolipid Metabolism in Liver." Frontiers in Pharmacology 13 (August 17, 2022). http://dx.doi.org/10.3389/fphar.2022.916603.
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Sweet taste receptors (STRs) play an important role in glucose metabolism, and type 2 diabetic rats have abnormal expressions of STRs in multiple tissues. Astragalus polysaccharides (APS) has shown a significant therapeutic effect on type 2 diabetes mellitus (T2DM), but its mechanism needs to be further clarified. T2DM rat model was induced by intraperitoneal streptozotocin injection and treated with APS for 8 weeks. Daily indicators of experimental rats were observed, and expression levels of STRs and genes related to glycolipid metabolism were determined by real-time quantitative PCR and western blot. The present study revealed that APS alleviated the symptoms of T2DM rats, improved HOMA-IR and promoted insulin secretion. Gene expression analysis found that APS significantly increased the expressions of signaling molecules in STRs pathways, including taste receptor family 1 member 2 (T1R2), α-gustducin (Gα) and transient receptor potential cation channel subfamily member 5 (TRPM5), and reversed the expressions of genes related to glucolipid metabolism, including glucose transporters 2 and 4 (GLUT2 and GLUT4), pyruvate carboxylase (PC), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) in the liver of T2DM rats. However, APS had no influences on the expressions of genes, including glycogen synthase kinase-3 beta (GSK-3β), pyruvate kinase (PK) and phosphoenolpyruvate carboxykinase (PEPCK) in the liver of T2DM rats. These results suggested that the physiological roles of STRs in the liver were involved with glucose transport and metabolism. APS alleviated T2DM rats by activating the STRs pathway, and promoted glucose transport and lipogenesis.
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Georgoulis, Ioannis, Christian Bock, Gisela Lannig, Hans O. Pörtner, Konstantinos Feidantsis, Ioannis A. Giantsis, Inna Sokolova, and Basile Michaelidis. "Metabolic remodeling caused by heat-hardening in the Mediterranean mussel Mytilus galloprovincialis." Journal of Experimental Biology, November 25, 2022. http://dx.doi.org/10.1242/jeb.244795.
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Organisms can faster and more efficiently modify and increase their thermal tolerance after a brief exposure to sublethal thermal stress. This response is called “heat-hardening” as it leads to the generation of phenotypes with increased heat tolerance. The aim of the study was to investigate the impact of heat-hardening on the metabolomic profile of M. galloprovincialis in order to identify the undergoing adjustments of biochemical pathways that might benefit mussels’ thermal tolerance. Thus, mussels were exposed sequentially to two different phases (heat-hardening and acclimation phases). To gain further insights into the possible mechanisms underlying the metabolic response of the heat-hardened M. galloprovincialis, metabolomics analysis was complemented by the estimation of mRNA expression of phosphoenolpyruvate carboxykinase (PEPCK), pyruvate kinase (PK) and alternative oxidase (AOX) implicated in the metabolic pathways of gluconeogenesis, glycolysis and redox homeostasis, respectively. Heat-hardened mussels showed evidence of higher activity of tricarboxylic acid (TCA) cycle and diversification of upregulated metabolic pathways, possibly as a mechanism to increase ATP production and extend survival under heat stress. Moreover, formate and taurine accumulation provide an antioxidant and cytoprotective role in mussels during hypoxia and thermal stress. Overall, the metabolic responses in non- and heat-hardened mussels underline the upper thermal limits of M. galloprovincialis, set at 26°C, and are in accordance with the OCLTT concept. The ability of heat-hardened mussels for a rapid gain and slow loss of heat tolerance may be an advantageous strategy for coping with the intermittent, and often extreme temperatures.
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Zeng, Ningmei, Jiankang Bao, TingTing Shu, Chuang Shi, Gang Zhai, Xia Jin, Jiangyan He, Qiyong Lou, and Zhan Yin. "Sexual dimorphic effects of igf1 deficiency on metabolism in zebrafish." Frontiers in Endocrinology 13 (July 29, 2022). http://dx.doi.org/10.3389/fendo.2022.879962.
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Insulin-like growth factor 1 (IGF1) is an essential effector of the growth hormone (GH)/IGF1 axis for somatic growth regulation in mammals. However, its functions have not been thoroughly investigated in zebrafish in vivo. In this study, the igf1-deficient zebrafish model was developed using the CRISPR/Cas9 technique. In this study all the results were performed on both male and female animals. The growth of both male and female igf1-deficient zebrafish were reduced. The igf1 deficiency leads to significant complementary up-regulation of transcriptional expression levels of insulin, igf2 and igf3. This suggested that igf2 and igf3 may act with redundant functions. While the upregulation of gh1 expression can only be detected in igf1-deficient females. At the same time, significant growth retardation, fatty liver, reduced activated levels of ribosomal S6 (S6) are seen only in igf1-deficient males. On the other hand, significant hyperglycemia, elevated transcriptional expression levels of phosphenolpyruvate carboxykinase (pepck) and levels of phosphorylated extracellular signal-regulated kinase (ERK1/2), with additional reduced hepatic lactate/pyruvate (L/P) ratios can only observed in igf1-deficient females. Impaired glucose uptake has been recorded in the primary cultured hepatocytes from igf1-deficient females, but not males. Intriguingly, exposure to 17beta-estroadiol (E2) can partially ameliorated the defects of fatty liver and activation of AKT/mTOR signaling in igf1-deficient males. Our studies demonstrate the significant functions of IGF1 on somatic regulation in zebrafish, with asymmetric gender-related consequences. Our data thus suggest that the zebrafish IGF1 is preferentially required for the activation of AKT/mTOR signaling in male zebrafish, but glucose uptake in females.