Glycogen

Distribution by Scientific Domains
Distribution within Life Sciences

Kinds of Glycogen

  • hepatic glycogen
  • liver glycogen
  • muscle glycogen

  • Terms modified by Glycogen

  • glycogen accumulation
  • glycogen breakdown
  • glycogen concentration
  • glycogen content
  • glycogen depletion
  • glycogen granule
  • glycogen level
  • glycogen metabolism
  • glycogen particle
  • glycogen phosphorylase
  • glycogen storage
  • glycogen storage disease type ia
  • glycogen store
  • glycogen synthase
  • glycogen synthase kinase
  • glycogen synthesis

  • Selected Abstracts


    The regulation of muscle glycogen: the granule and its proteins

    ACTA PHYSIOLOGICA, Issue 4 2010
    T. E. Graham
    Abstract Despite decades of studying muscle glycogen in many metabolic situations, surprisingly little is known regarding its regulation. Glycogen is a dynamic and vital metabolic fuel that has very limited energetic capacity. Thus its regulation is highly complex and multifaceted. The stores in muscle are not homogeneous and there appear to be various metabolic pools. Each granule is capable of independent regulation and fundamental aspects of the regulation appear to be associated with a complex set of proteins (some are enzymes and others serve scaffolding roles) that associate both with the granule and with each other in a dynamic fashion. The regulation includes altered phosphorylation status and often translocation as well. The understanding of the roles and the regulation of glycogenin, protein phosphatase 1, glycogen targeting proteins, laforin and malin are in their infancy. These various processes appear to be the mechanisms that give the glycogen granule precise, yet dynamic regulation. [source]


    Glycogen: A novel branched polysaccharide chiral selector in CE

    ELECTROPHORESIS, Issue 6 2010
    Jiaquan Chen
    Abstract Various chiral selectors have been employed in CE and among them linear polysaccharides exhibited powerful enantioselective properties. Different from linear polysaccharides, the use of branched polysaccharides as chiral selectors in CE has not been reported previously. In this study glycogen belonging to the class of branched polysaccharides was used as a novel chiral selector for the enantiomeric separations for the first time. Since glycogen is electrically neutral, the method is applicable to ionic compounds. Eighteen chiral compounds including 12 basic drugs and six acidic drugs have been tested to demonstrate the potential of this chiral selector. BGE and selector concentrations and buffer pH were systematically optimized in order to obtain successful chiral separations. Among the tested compounds, the enantiomers of ibuprofen, which is an acidic drug, were successfully recognized by 3.0%,w/v glycogen with 90,mM Tris-H3PO4 buffer (pH 7.0). The enantiomers of basic drugs such as citalopram, cetirizine and nefopam were also baseline-resolved with 50,mM Tris-H3PO4 buffer (pH 3.0) containing 3.0% glycogen. Amlodipine belonging to basic compound only gave partial enantioseparation under the above-mentioned condition. [source]


    Ultrastructure of the embryonic snake skin and putative role of histidine in the differentiation of the shedding complex

    JOURNAL OF MORPHOLOGY, Issue 2 2002
    Lorenzo Alibardi
    Abstract The morphogenesis and ultrastructure of the epidermis of snake embryos were studied at progressive stages of development through hatching to determine the time and modality of differentiation of the shedding complex. Scales form as symmetric epidermal bumps that become slanted and eventually very overlapped. During the asymmetrization of the bumps, the basal cells of the forming outer surface of the scale become columnar, as in an epidermal placode, and accumulate glycogen. Small dermal condensations are sometimes seen and probably represent primordia of the axial dense dermis of the growing tip of scales. Deep, dense, and superficial loose dermal regions are formed when the epidermis is bilayered (periderm and basal epidermis) and undifferentiated. Glycogen and lipids decrease from basal cells to differentiating suprabasal cells. On the outer scale surface, beneath the peridermis, a layer containing dense granules and sparse 25,30-nm thick coarse filaments is formed. The underlying clear layer does not contain keratohyalin-like granules but has a rich cytoskeleton of intermediate filaments. Small denticles are formed and they interdigitate with the oberhautchen spinulae formed underneath. On the inner scale surface the clear layer contains dense granules, coarse filaments, and does not form denticles with the aspinulated oberhautchen. On the inner side surface the oberhautchen only forms occasional spinulae. The sloughing of the periderm and embryonic epidermis takes place in ovo 5,6 days before hatching. There follow beta-, mesos-, and alpha-layers, not yet mature before hatching. No resting period is present but a new generation is immediately produced so that at 6,10 h posthatching an inner generation and a new shedding complex are forming beneath the outer generation. The first shedding complex differentiates 10,11 days before hatching. In hatchlings 6,10 h old, tritiated histidine is taken up in the epidermis 4 h after injection and is found mainly in the shedding complex, especially in the apposed membranes of the clear layer and oberhautchen cells. This indicates that a histidine-rich protein is produced in preparation for shedding, as previously seen in lizard epidermis. The second shedding (first posthatching) takes place at 7,9 days posthatching. It is suggested that the shedding complex in lepidosaurian reptiles has evolved after the production of a histidine-rich protein and of a beta-keratin layer beneath the former alpha-layer. J. Morphol. 251:149,168, 2002. © 2002 Wiley-Liss, Inc. [source]


    The utilization of glycogen accumulating organisms for mixed culture production of polyhydroxyalkanoates

    BIOTECHNOLOGY & BIOENGINEERING, Issue 4 2009
    *Article first published online: 15 JUN 200, Simon Bengtsson
    Abstract Production of polyhydroxyalkanoates (PHAs) by an open mixed culture enriched in glycogen accumulating organisms (GAOs) under alternating anaerobic,aerobic conditions with acetate as carbon source was investigated. The culture exhibited a stable enrichment performance over the 450-day operating period with regards to phenotypic behavior and microbial community structure. Candidatus Competibacter phosphatis dominated the culture at between 54% and 70% of the bacterial biomass throughout the study, as determined by fluorescence in situ hybridization. In batch experiments under anaerobic conditions, PHA containing 3-hydroxybutyrate (3HB) and 27,mol-% 3-hydroxyvalerate (3HV) was accumulated up to 49% of cell dry weight utilizing the glycogen pool stored in the SBR cycle. Under aerobic and ammonia limited conditions, PHA comprising only 3HB was accumulated to 60% of cell dry weight. Glycogen was consumed during aerobic PHA accumulation as well as under anaerobic conditions, but with different stoichiometry. Under aerobic conditions 0.31 C-mol glycogen was consumed per consumed C-mol acetate compared to 0.99 under anaerobic conditions. Both the PHA biomass content and the specific PHA production rate obtained were similar to what is typically obtained using the more commonly applied aerobic dynamic feeding strategy. Biotechnol. Bioeng. 2009; 104: 698,708 © 2009 Wiley Periodicals, Inc. [source]


    Evidence that glutamine is involved in neutrophil function

    CELL BIOCHEMISTRY AND FUNCTION, Issue 2 2002
    Tania C. Pithon-Curi
    Abstract Phosphate-dependent glutaminase (PDG) activity, a key enzyme of glutamine metabolism, was determined in neutrophils obtained from the intra-peritoneal cavity (PC) or bronchoalveolar space (BAS) after administration of 1,ml or 100,,l, respectively of saline, glycogen solution (1%) or lipopolysaccharide (LPS 0.1,mg (100,,l),1). Neutrophils were obtained by lavage of both sites with 20,ml saline 24,h after the administration of the stimuli. Glycogen and LPS, depending on the site the cells were obtained from, differently modulated PDG activity. Cells from BAS stimulated by glycogen or LPS had raised PDG activity to 30.5,±,5.2 and 42.7,±,12.1,nmol,min,1,mg,1 protein, respectively, when compared with saline (9.1,±,0.9,nmol,min,1,mg,1 protein); mean,±,SEM. On the other hand, cells from PC showed different PDG activity: 52.0,±,12.6,nmol,min,1,mg,1 for saline, 36.5,±,9.5,nmol,min,1,mg,1 for glycogen, and 76.6,±,11.2,nmol,min,1,mg,1 for LPS; mean,±,SEM. Therefore, PDG activity varies with the site from which neutrophils are obtained and the stimulus imposed. The effect of glutamine on nitric oxide (NO) and tumour necrosis factor (TNF) production by peritoneal neutrophils, obtained after glycogen administration, cultured in the presence of LPS (0.5,,g,ml,1) was also examined. The addition of glutamine at concentrations varying from 2 to 20,mM did not markedly affect NO production. Glutamine alone at 2,mM did not modify the production of TNF but in the presence of LPS caused a significant decrease. So, glutamine may preserve the function of neutrophils during infections and injuries. Copyright © 2001 John Wiley & Sons, Ltd. [source]


    Effects of oyster extract on the reproductive function of zinc-deficient mice: Bioavailability of zinc contained in oyster extract

    CONGENITAL ANOMALIES, Issue 4 2003
    Yoshikazu Matsuda
    ABSTRACT Zinc is a vital nutrient in the normal reproductive function and embryonic development of mammals, and it is well known that oyster extract contains significant amounts of zinc. The effects of oyster extract on reproductive function, such as embryonic development, serum levels of zinc and sperm maturation were examined in zinc-deficient mice. Zinc deficiency in dams during pregnancy induced a decrease in the successful pregnancy rate, maternal weight gain, the number of live fetuses and fetal body weight. Zinc deficiency for 12 weeks in male mice induced a decrease in body weight, testis weight and sperm count in the epididymis. However, reproductive failure, embryonic defects and decreased sperm motility in zinc-deficient mice were improved by supplementation with oyster extract. Some nutrients contained in oyster extract, such as taurine and glycogen, may be related to the recovery of reproductive function. There were significantly lower serum concentrations of zinc in dams fed a zinc-deficient diet However, the serum zinc concentration was normal in the oyster extract-supplemented group. No difference in the concentration of serum zinc was observed between the oyster extract- and zinc carbonate-supplemented groups. From these findings, it is suggested that oyster extract is a useful supplement that can prevent reproductive defects from zinc deficiency, and the bioavailability of zinc may be identical to zinc carbonate. [source]


    The regulation of muscle glycogen: the granule and its proteins

    ACTA PHYSIOLOGICA, Issue 4 2010
    T. E. Graham
    Abstract Despite decades of studying muscle glycogen in many metabolic situations, surprisingly little is known regarding its regulation. Glycogen is a dynamic and vital metabolic fuel that has very limited energetic capacity. Thus its regulation is highly complex and multifaceted. The stores in muscle are not homogeneous and there appear to be various metabolic pools. Each granule is capable of independent regulation and fundamental aspects of the regulation appear to be associated with a complex set of proteins (some are enzymes and others serve scaffolding roles) that associate both with the granule and with each other in a dynamic fashion. The regulation includes altered phosphorylation status and often translocation as well. The understanding of the roles and the regulation of glycogenin, protein phosphatase 1, glycogen targeting proteins, laforin and malin are in their infancy. These various processes appear to be the mechanisms that give the glycogen granule precise, yet dynamic regulation. [source]


    Evidence against a sexual dimorphism in glucose and fatty acid metabolism in skeletal muscle cultures from age-matched men and post-menopausal women

    ACTA PHYSIOLOGICA, Issue 3 2009
    A. Rune
    Abstract Aim:,In vivo whole body differences in glucose/lipid metabolism exist between men and women. Thus, we tested the hypothesis that intrinsic sex differences exist in skeletal muscle gene expression and glucose/lipid metabolism using cultured myotubes. Methods:, Myotube cultures were prepared for gene expression and metabolic studies from vastus lateralis skeletal muscle biopsies obtained from age-matched men (n = 11; 59 ± 2 years) and post-menopausal women (n = 10; 60 ± 1 years). Results:, mRNA expression of several genes involved in glucose and lipid metabolism was higher in skeletal muscle biopsies from female vs. male donors, but unaltered between the sexes in cultured myotubes. Basal and insulin-stimulated glucose uptake, as well as glucose incorporation into glycogen, was similar in myotube cultures derived from male vs. female donors. In males vs. females, insulin increased glucose uptake (1.3 ± 0.1 vs. 1.5 ± 0.1-fold respectively) and incorporation into glycogen (2.3 ± 0.3 vs. 2.0 ± 0.3-fold respectively) to the same extent. Basal fatty acid oxidation and rate of uptake/accumulation was similar between sexes. In response to the 5,AMP-activated protein kinase activator AICAR, lipid oxidation was increased to the same extent in myotubes established from male vs. female donors (1.6 ± 0.6 vs. 2.0 ± 0.3-fold respectively). Moreover, the AICAR-induced rate of uptake/accumulation was similar between sexes. Conclusion:, Differences in metabolic parameters and gene expression profiles between age-matched men and post-menopausal women noted in vivo are not observed in cultured human skeletal muscle cells. Thus, the sexual dimorphism in glucose and lipid metabolism is likely a consequence of systemic whole body factors, rather than intrinsic differences in the skeletal muscle proper. [source]


    Impact of carbohydrate supplementation during endurance training on glycogen storage and performance

    ACTA PHYSIOLOGICA, Issue 2 2009
    L. Nybo
    Abstract Aim:, Glucose ingestion may improve exercise endurance, but it apparently also influences the transcription rate of several metabolic genes and it alters muscle metabolism during an acute exercise bout. Therefore, we investigated how chronic training responses are affected by glucose ingestion. Methods:, In previously untrained males performance and various muscular adaptations were evaluated before and after 8 weeks of supervised endurance training conducted either with (n = 8; CHO group) or without (n = 7; placebo) glucose supplementation. Results:, The two groups achieved similar improvements in maximal oxygen uptake and peak power output during incremental cycling (both parameters elevated by 17% on average) and both groups lost ,3 kg of fat mass during the 8 weeks of training. An equal reduction in respiratory exchange ratio (0.02 units) during submaximal exercise was observed in both groups. Beta-hydroxyacyl-CoA-dehydrogenase activity was increased in both groups, however, to a larger extent in the placebo group (45 ± 11%) than CHO (23 ± 9%, P < 0.05). GLUT-4 protein expression increased by 74 ± 14% in the placebo group and 45 ± 14% in CHO (both P < 0.05), while resting muscle glycogen increased (P < 0.05) to a larger extent in the placebo group (96 ± 4%) than CHO (33 ± 2%). Conclusion:, These results show that carbohydrate supplementation consumed during exercise training influences various muscular training adaptations, but improvements in cardiorespiratory fitness and reductions in fat mass are not affected. [source]


    AMP-activated protein kinase , a sensor of glycogen as well as AMP and ATP?

    ACTA PHYSIOLOGICA, Issue 1 2009
    A. McBride
    Abstract The classical role of the AMP-activated protein kinase (AMPK) is to act as a sensor of the immediate availability of cellular energy, by monitoring the concentrations of AMP and ATP. However, the , subunits of AMPK contain a glycogen-binding domain, and in this review we develop the hypothesis that this is a regulatory domain that allows AMPK to act as a sensor of the status of cellular reserves of energy in the form of glycogen. We argue that the pool of AMPK that is bound to the glycogen particle is in an active state when glycogen particles are fully synthesized, causing phosphorylation of glycogen synthase at site 2 and providing a feedback inhibition of further extension of the outer chains of glycogen. However, when glycogen becomes depleted, the glycogen-bound pool of AMPK becomes inhibited due to binding to ,1,6-linked branch points exposed by the action of phosphorylase and/or debranching enzyme. This allows dephosphorylation of site 2 on glycogen synthase by the glycogen-bound form of protein phosphatase-1, promoting rapid resynthesis of glycogen and replenishment of glycogen stores. This is an extension of the classical role of AMPK as a ,guardian of cellular energy', in which it ensures that cellular energy reserves are adequate for medium-term requirements. The literature concerning AMPK, glycogen structure and glycogen-binding proteins that led us to this concept is reviewed. [source]


    Changes in skeletal muscle size, fibre-type composition and capillary supply after chronic venous occlusion in rats

    ACTA PHYSIOLOGICA, Issue 4 2008
    S. Kawada
    Abstract Aim:, We have previously shown that surgical occlusion of some veins from skeletal muscle results in muscle hypertrophy without mechanical overloading in the rat. The present study investigated the changes in muscle-fibre composition and capillary supply in hypertrophied muscles after venous occlusion in the rat hindlimb. Methods:, Sixteen male Wistar rats were randomly assigned into two groups: (i) sham operated (sham-operated group; n = 7); (ii) venous occluded for 2 weeks (2-week-occluded group; n = 9). At the end of the experimental period, specimens of the plantaris muscle were dissected from the hindlimbs and subjected to biochemical and histochemical analyses. Results:, Two weeks after the occlusion, both the wet weight of plantaris muscle relative to body weight and absolute muscle weight showed significant increases in the 2-week-occluded group (,15%) when compared with those in the sham-operated group. The concentrations of muscle glycogen and lactate were higher in the 2-week-occluded group, whereas staining intensity of muscle lipid droplets was lower in the 2-week-occluded group than those in the sham-operated group. The percentage of type I muscle fibre decreased, whereas that of type IIb fibre increased in the 2-week-occluded group when compared with the sham-operated group. Although the expression of vascular endothelial growth factor-188 mRNA increased, the number of capillaries around the muscle fibres tended to decrease (P = 0.07). Conclusion:, Chronic venous occlusion causes skeletal muscle hypertrophy with fibre-type transition towards faster types and changes in contents of muscle metabolites. [source]


    The relationship between peripheral glucose utilisation and insulin sensitivity in the regulation of hepatic glucose production: studies in normal and alloxan-diabetic dogs

    DIABETES/METABOLISM: RESEARCH AND REVIEWS, Issue 2 2006
    M. J. Christopher
    Abstract Background Hepatic glucose overproduction (HGP) of diabetes could be primary or could occur in response to the metabolic needs of peripheral (skeletal muscle (SkM)) tissues. This question was tested in normal and diabetic dogs. Methods HGP, SkM glucose uptake (Rdtissue), metabolic clearance of glucose (MCRg) and glycolytic flux (GFexog), and SkM biopsies were measured in the same dogs before and after alloxan-induced diabetes. Normal dogs were exposed to (1) an extended 20-h fast, (2) low- and high-dose glucose infusions (GINF) at basal insulinaemia, and chronic diabetic dogs were exposed to (3) hyperglycaemia, (4) phlorizin-induced normoglycaemia, and (5) poor and good diabetic control. Results (1) Prolonged fast: HGP, Rdtissue, and GFexog fell in parallel (p < 0.05). (2) Low-dose GINF: plasma glucose, insulin, Rdtissue, MCRg, and GFexog were unchanged, but HGP fell by ,40%, paralleling the supplemental GINF. (3) High-dose GINF at basal insulin: plasma glucose doubled and synchronous changes in HGP, Rdtissue, MCRg, and GFexog occurred; ICglucose, G6P, and glycogen were unchanged. (4) Hyperglycaemic diabetes: HGP was raised (p < 0.05), matching urinary glucose loss (UGL) and decreased MCRg, and maintaining normal basal Rdtissue and GFexog. SkM ICglucose was increased and glycogen decreased (both p < 0.05). (5) Phlorizin-induced normoglycaemia in diabetic dogs: HGP rose, matching the increased UGL, while maintaining normal Rdtissue and GFexog. Intramuscular substrates normalised. (6) Whole body and SkM metabolism normalised with correction of the insulin resistance and good diabetic control. Conclusion HGP reflects whether SkM is in a state of relative glucose ,excess' or absolute/relative glucose ,deprivation'. Copyright © 2005 John Wiley & Sons, Ltd. [source]


    Insulino-mimetic and anti-diabetic effects of vanadium compounds

    DIABETIC MEDICINE, Issue 1 2005
    A. K. Srivastava
    Abstract Compounds of the trace element vanadium exert various insulin-like effects in in vitro and in vivo systems. These include their ability to improve glucose homeostasis and insulin resistance in animal models of Type 1 and Type 2 diabetes mellitus. In addition to animal studies, several reports have documented improvements in liver and muscle insulin sensitivity in a limited number of patients with Type 2 diabetes. These effects are, however, not as dramatic as those observed in animal experiments, probably because lower doses of vanadium were used and the duration of therapy was short in human studies as compared with animal work. The ability of these compounds to stimulate glucose uptake, glycogen and lipid synthesis in muscle, adipose and hepatic tissues and to inhibit gluconeogenesis, and the activities of the gluconeogenic enzymes: phosphoenol pyruvate carboxykinase and glucose-6-phosphatase in the liver and kidney as well as lipolysis in fat cells contributes as potential mechanisms to their anti-diabetic insulin-like effects. At the cellular level, vanadium activates several key elements of the insulin signal transduction pathway, such as the tyrosine phosphorylation of insulin receptor substrate-1, and extracellular signal-regulated kinase 1 and 2, phosphatidylinositol 3-kinase and protein kinase B activation. These pathways are believed to mediate the metabolic actions of insulin. Because protein tyrosine phosphatases (PTPases) are considered to be negative regulators of the insulin-signalling pathway, it is suggested that vanadium can enhance insulin signalling and action by virtue of its capacity to inhibit PTPase activity and increase tyrosine phosphorylation of substrate proteins. There are some concerns about the potential toxicity of available inorganic vanadium salts at higher doses and during long-term therapy. Therefore, new organo-vanadium compounds with higher potency and less toxicity need to be evaluated for their efficacy as potential treatment of human diabetes. [source]


    Spermiogenesis and spermatozoon ultrastructure of the davaineid cestode Raillietina micracantha (Fuhrmann, 1909)

    ACTA ZOOLOGICA, Issue 2 2010
    Jordi Miquel
    Abstract Miquel, J., Torres, J., Foronda, P. and Feliu, C. 2010. Spermiogenesis and spermatozoon ultrastructure of the davaineid cestode Raillietina micracantha. , Acta Zoologica (Stockholm) 91: 212,221 The spermiogenesis and the ultrastructural organization of the spermatozoon of the davaineid cestode Raillietina micracantha are described by means of transmission electron microscopy. Spermiogenesis begins with the formation of a zone of differentiation containing two centrioles. One of the centrioles develops a free flagellum that later fuses with a cytoplasmic extension. The nucleus migrates along the spermatid body after the proximodistal fusion of the flagellum and the cytoplasmic extension. During advanced stages of spermiogenesis a periaxonemal sheath and intracytoplasmic walls appear in the spermatids. Spermiogenesis finishes with the appearance of two helicoidal crested bodies at the base of spermatids and, finally, the narrowing of the ring of arched membranes detaches the fully formed spermatozoon. The mature spermatozoon of R. micracantha is a long and filiform cell, tapered at both ends, which lacks mitochondria. It exhibits two crested bodies of different lengths, one axoneme of the 9 + ,1' pattern of trepaxonematan Platyhelminthes, twisted cortical microtubules, a periaxonemal sheath, intracytoplasmic walls, granules of glycogen and a spiralled nucleus. The anterior extremity of the spermatozoon is characterized by the presence of an electron-dense apical cone and two spiralled crested bodies while the posterior extremity of the male gamete exhibits only the axoneme and an electron-dense posterior tip. [source]


    Ultrastructure and functional features of midgut of an adult water mite Teutonia cometes (Koch, 1837) (Hydrachnidia: Teutoniidae)

    ACTA ZOOLOGICA, Issue 2 2010
    Andrew B. Shatrov
    Abstract Shatrov, A. B. 2010. Ultrastructure and functional features of midgut of an adult water mite Teutonia cometes (Koch 1837) (Hydrachnidia: Teutoniidae). ,Acta Zoologica (Stockholm) 91: 222,232 The midgut of the adult water mite Teutonia cometes (Koch 1837) (Hydrachnidia: Teutoniidae) was investigated by means of transmission electron microscopy and on semi-thin sections. The midgut is represented by a blind sac composed of the narrow ventriculus, two proventricular lateral diverticula and three pairs of postventricular caeca. A single-layered epithelium consists of one type of endodermal digestive cells of quite different shape and size, which may form protrusions into the midgut lumen. The large nuclei are frequently lobed and contain one to three nucleoli. The apical cell membrane forms short scarce microvilli, between their bases the pinocytotic vesicles of unspecific macropinocytosis as well as the narrow pinocytotic canals are formed and immersed into the cell. The intracellular digestion of the food ingested into the midgut after extraintestinal digestion is predominant. The pinocytotic vesicles fuse with small clear vesicles of proposed Golgi origin to form secondary lysosomes. The digestive cells also contain small amounts of rough endoplasmic reticulum, variously structured heterolysosomes, residual materials in the form of both the small electron-dense bodies and the large variously granulated substances, reserve nutritive materials such as lipid and glycogen, as well as clear vacuoles. Residual materials are obviously extruded from the cells into the gut lumen. [source]


    Glycogen: A novel branched polysaccharide chiral selector in CE

    ELECTROPHORESIS, Issue 6 2010
    Jiaquan Chen
    Abstract Various chiral selectors have been employed in CE and among them linear polysaccharides exhibited powerful enantioselective properties. Different from linear polysaccharides, the use of branched polysaccharides as chiral selectors in CE has not been reported previously. In this study glycogen belonging to the class of branched polysaccharides was used as a novel chiral selector for the enantiomeric separations for the first time. Since glycogen is electrically neutral, the method is applicable to ionic compounds. Eighteen chiral compounds including 12 basic drugs and six acidic drugs have been tested to demonstrate the potential of this chiral selector. BGE and selector concentrations and buffer pH were systematically optimized in order to obtain successful chiral separations. Among the tested compounds, the enantiomers of ibuprofen, which is an acidic drug, were successfully recognized by 3.0%,w/v glycogen with 90,mM Tris-H3PO4 buffer (pH 7.0). The enantiomers of basic drugs such as citalopram, cetirizine and nefopam were also baseline-resolved with 50,mM Tris-H3PO4 buffer (pH 3.0) containing 3.0% glycogen. Amlodipine belonging to basic compound only gave partial enantioseparation under the above-mentioned condition. [source]


    The Male Accessory Gland Substances of Lucilia illustris (I): Its Effect on Mating Receptivity

    ENTOMOLOGICAL RESEARCH, Issue 2 2002
    Jong-Jin LEE
    ABSTRACT In order to verify the physiological functions of male accessory gland (MAG) substances of the blowfly, Lucilia illustris Meigen, the growth and changes in metabolites of male accessory gland with aging, and the effect of male accessory gland extract on mating receptivity of L. illustris were examined. There was not a significant difference in length of MAG with aging, but the width of MAG was grown widely from 0 to 5-days old apparently. Changes in glycogen, total protein and lipid of male accessory gland substances showed same patterns but total protein content was higher than the others. Therefore, male nutrition affected the production of male accessory proteins. During the mating fed unmated male transferred larger amount of protein than that of starved male. When male accessory gland homogenates injected, mating receptivity of gravid female was greatly inhibited comparing to control, suggesting that the accessory gland substances of L. illustris alters female mating receptivity after mating. [source]


    Investigation of histopathological and cytogenetic effects on Lepomis gibbosus (Pisces: Perciformes) in the Çine stream (Ayd,n/Turkey) with determination of water pollution

    ENVIRONMENTAL TOXICOLOGY, Issue 6 2005
    Yücel Ba, lu Koca
    Abstract Water quality and the distribution of some heavy metals in three different organs of Lepomis gibbosus from the Çine Stream were studied. Also, histopathological changes in gill, liver, and muscle tissue were examined at light microscopical level. Micronucleus (MN) formation in fish erytrocytes, as an indicator of chromosomal damage, has been increasingly used to detect the genotoxic potential of environmental contaminants. The frequency of MN was examined from samples of fish from the Çine Stream and a control group. MN frequency was higher in fish samples caught from the Çine Stream than that in the control group. The chemicals ammonia, nitrite, nitrate, orthophosphate, and sulphate were determined as parameters that possibly affect the gill, liver, and muscle morphology. Zn was the most accumulated metal in tissues as well as in water. Maximum metal accumulation occured in both liver and gills. For histopathological examinations, samples of gills, liver, and muscle tissues of L. gibbosus were studied by using light microscopy. In this study, a significant decrease in mean length of primary and secondary lamellae were observed. Moreover, cellular proliferation developed with secondary lamellae fusion, ballooning degenerations or club deformation of secondary lamellae, as well as distribution of necrotic, hyperplastic and clavate secondary lamellae. In the liver, altered staining, swollen and ruptured parenchymal cells, loss of cord structure, reduce of glycogen in hepatocytes, and vacuolar structure filled with cellular debris and many dark particles were seen. In muscle tissue, focal necrosis, cellular dissolution, and a decline or loss of striatation in muscle fibres were found. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 560,571, 2005. [source]


    Tolerance to metals and assessment of energy reserves in the polychaete Nereis diversicolor in clean and contaminated estuaries

    ENVIRONMENTAL TOXICOLOGY, Issue 1 2005
    C. Durou
    Abstract Estuaries are subject to anthropogenic activities. Because the intrasedimentary worm Nereis diversicolor has ecological characteristics and bioindicator abilities, its use was pertinent in investigating the concepts and cost of tolerance to heavy metals (Cd, Cu, Zn). In this context, two approaches were carried out, performing toxicity tests and estimating energy reserves (glycogen and lipids), in populations originating from a contaminated site (Seine estuary) compared with those from a clean site (Authie estuary). Mean lethal times (LT50s) of organisms exposed to zinc from the Seine estuary were higher than those from the Authie estuary, but not of organisms exposed to Cd or Cu. The influence of animal weight and salinity on the sensitivity of worms also was studied. The biggest worms were more tolerant to zinc than the smallest ones, and worms survived longer at a reduced salinity (15,). Concentrations of glycogen and lipids in each sampling season were higher in specimens from the Authie estuary than in worms from the Seine estuary. No influence of salinity on glycogen and lipid levels was observed. Glycogen concentrations were not influenced by the weight of specimens, whereas lipid concentrations were significantly and positively correlated with weight. In conclusion, worms from the Seine estuary exhibited tolerance to Zn, and the depletion of energy reserves observed in this population could be interpreted as a cost of tolerance. © 2005 Wiley Periodicals, Inc. Environ Toxicol 20: 23,31, 2005. [source]


    Impact of microcystin containing diets on physiological performance of Nile tilapia (Oreochromis niloticus) concerning stress and growth,

    ENVIRONMENTAL TOXICOLOGY & CHEMISTRY, Issue 3 2010
    Andrea Ziková
    Abstract Diets containing Microcystis with considerable amounts of the cyanotoxin microcystin-LR (MC-LR) were fed to determine their impact on the physiological performance of the omnivorous Nile tilapia (Oreochromis niloticus) with regard to stress and growth performance. Four different diets were prepared based on a commercial diet (control, MC-5% [containing 5% dried Microcystis biomass], MC-20% [containing 20% dried Microcystis biomass], and Arthrospira-20% [containing 20% dried Arthrospira sp. biomass without toxin]) and fed to female Nile tilapia. Blood and tissue samples were taken after 1, 7, and 28 d, and MC-LR was quantified in gills, muscle, and liver by using high-performance liquid chromatography (HPLC). Only in the liver were moderate concentrations of MC-LR detected. The stress hormone cortisol and glucose were analyzed from plasma, suggesting that all modified diets caused only minor to moderate stress, which was confirmed by analyses of hepatic glycogen. In addition, the effects of the different diets on growth performance were investigated by determining gene expression of hypophyseal growth hormone (GH) and hepatic insulin-like growth factor-I (IGF-I). For all diets, quantitative reverse transcription-polymerase chain reaction (RT-qPCR) demonstrated no significant effect on gene expression of the major endocrine hormones of the growth axis, whereas classical growth data, including growth and feed conversion ratio, displayed slight inhibitory effects of all modified diets independent of their MC-LR content. However, no significant change was found in condition or hepatosomatic index among the various diets, so it seems feasible that dried cyanobacterial biomass might be even used as a component in fish diet for Nile tilapia, which requires further research in more detail. Environ. Toxicol. Chem. 2010;29:561,568. © 2009 SETAC [source]


    Effects of short-term training on insulin sensitivity and skeletal muscle glucose metabolism in Standardbred horses

    EQUINE VETERINARY JOURNAL, Issue S36 2006
    L. STEWART-HUNT
    Summary Reasons for performing study: Increased insulin sensitivity occurs after a period of exercise training, but the mechanisms underlying this training-associated increase in insulin action have not been investigated. Objective: To examine the effects of short-term endurance training (7 consecutive days) and a subsequent period of inactivity (5 days) on whole body insulin sensitivity and GLUT-4 protein and the activities of glycogen synthase (GS) and hexokinase (HK) in skeletal muscle. It was hypothesised that training would increase insulin sensitivity in association with increased GLUT-4 protein and activities of GS and HK, but that these changes would be transient, returning to baseline after 5 days of inactivity. Methods: Seven mature Standardbred horses completed training consisting of 7 consecutive days of 45 min of treadmill exercise at a speed that elicited 55% of pretraining maximal aerobic capacity (VO2peak). Insulin sensitivity was determined by rate of glucose disposal (M) during the last 60 min of a 120 min euglycaemic-hyperinsulinaemic clamp (EHC) performed before (-2 days) and at 1 and 6 days following training. VO2peak was measured before (UT) and after (TR) training and the period of inactivity (IA). Results: Training resulted in a 9% increase in mean VO2peak (P<0.05) that was maintained following inactivity (IA). Mean M values were more than 2-fold higher (P<0.05) in TR than in UT. Mean M was also higher (P<0.05) in IA when compared to UT. GLUT-4 protien abundancewas more than 10-fold higher in TR and IA (P<0.001) than in UT. Pre-EHC GS activity and GS fractional velocity were increased (P<0.05) in TR when compared to UT and IA. Pre-EHC HK activity was increased (P<0.05) in IA when compared to UT and TR. Muscle glycogen was 66% lower (P<0.05) in TR than in UT and IA. Conclusions: Short-term training resulted in increases in whole body insulin sensitivity, and GLUT-4 protein content and glycogen synthase activity in skeletal muscle. The enhancements in insulin sensitivity, GLUT-4 protein and glycogen synthase activity were still evident after 5 days of inactivity. Potential relevance: Insulin resistance in equids has been associated with obesity and predisposition to laminitis. Regular physical activity may mitigate risk of these conditions via enhancement of insulin sensitivity and/or control of bodyweight. [source]


    Acute signalling responses to intense endurance training commenced with low or normal muscle glycogen

    EXPERIMENTAL PHYSIOLOGY, Issue 2 2010
    Wee Kian Yeo
    We have previously demonstrated that well-trained subjects who completed a 3 week training programme in which selected high-intensity interval training (HIT) sessions were commenced with low muscle glycogen content increased the maximal activities of several oxidative enzymes that promote endurance adaptations to a greater extent than subjects who began all training sessions with normal glycogen levels. The aim of the present study was to investigate acute skeletal muscle signalling responses to a single bout of HIT commenced with low or normal muscle glycogen stores in an attempt to elucidate potential mechanism(s) that might underlie our previous observations. Six endurance-trained cyclists/triathletes performed a 100 min ride at ,70% peak O2 uptake (AT) on day 1 and HIT (8 × 5 min work bouts at maximal self-selected effort with 1 min rest) 24 h later (HIGH). Another six subjects, matched for fitness and training history, performed AT on day 1 then 1,2 h later, HIT (LOW). Muscle biopsies were taken before and after HIT. Muscle glycogen concentration was higher in HIGH versus LOW before the HIT (390 ± 28 versus 256 ± 67 ,mol (g dry wt),1). After HIT, glycogen levels were reduced in both groups (P < 0.05) but HIGH was elevated compared with LOW (229 ± 29 versus 124 ± 41 ,mol (g dry wt),1; P < 0.05). Phosphorylation of 5,AMP-activated protein kinase (AMPK) increased after HIT, but the magnitude of increase was greater in LOW (P < 0.05). Despite the augmented AMPK response in LOW after HIT, selected downstream AMPK substrates were similar between groups. Phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was unchanged for both groups before and after the HIT training sessions. We conclude that despite a greater activation AMPK phosphorylation when HIT was commenced with low compared with normal muscle glycogen availability, the localization and phosphorylation state of selected downstream targets of AMPK were similar in response to the two interventions. [source]


    Development of an Improved Technique for the Perfusion of the Isolated Caudal Lobe of Sheep Liver

    EXPERIMENTAL PHYSIOLOGY, Issue 5 2000
    A. M. Ali
    The study was designed to develop an improved technique for perfusing the isolated caudal lobe of sheep liver. Twenty caudal lobes were perfused for 3-4 h, in a non-recirculating mode, with Krebs-Henseleit bicarbonate buffer. The perfusion system was designed to give a constant flow. The hepatic viability and functional normality of the perfused lobe were assessed by measuring the perfusion flow rate, pH, K+ efflux, O2 uptake, substrate uptake, gluconeogenesis from propionate and amino acids, and ureagenesis from ammonia and amino acids. Liver tissue was sampled for histological examination, as well as for the determination of liver glycogen and wet: dry weight ratio. The perfusion flow rate and pH were both stable throughout the perfusion. The potassium concentration in the effluent perfusate did not increase during the perfusion, suggesting that there was no loss of viability or hypoxia. The perfused lobe extracted more than 50% of the O2 supply. The rate of oxygen consumption was comparable to the rate reported in vivo. The initial glycogen content was reduced by about 40% after 4 h perfusion. The wet: dry weight ratio was 3.6, consistent with the absence of tissue oedema. Urea production was stimulated when NH4Cl (0.3 mM) was added to the medium but there was no significant increase in urea release when alanine (0.15 mM), glutamine (0.2 mM) or lysine (0.2 mM) was added. Urea production, however, increased by about 171% when a physiological mixture of amino acids was added. Propionate (0.5 mM), alanine and glutamine stimulated glucose production but not lysine or the complete amino acid mixture. Glutamine release was lower than that reported in the rat liver. Changing the direction of flow also revealed an apparent difference between livers from sheep and rats in their metabolism of ammonia. The improved technique offers a simple practical and inexpensive approach to many problems in ruminant physiology and nutritional biochemistry. [source]


    Anaerobic homolactate fermentation with Saccharomyces cerevisiae results in depletion of ATP and impaired metabolic activity

    FEMS YEAST RESEARCH, Issue 3 2009
    Derek A. Abbott
    Abstract Conversion of glucose to lactic acid is stoichiometrically equivalent to ethanol formation with respect to ATP formation from substrate-level phosphorylation, redox equivalents and product yield. However, anaerobic growth cannot be sustained in homolactate fermenting Saccharomyces cerevisiae. ATP-dependent export of the lactate anion and/or proton, resulting in net zero ATP formation, is suspected as the underlying cause. In an effort to understand the mechanisms behind the decreased lactic acid production rate in anaerobic homolactate cultures of S. cerevisiae, aerobic carbon-limited chemostats were performed and subjected to anaerobic perturbations in the presence of high glucose concentrations. Intracellular measurements of adenosine phosphates confirmed ATP depletion and decreased energy charge immediately upon anaerobicity. Unexpectedly, readily available sources of carbon and energy, trehalose and glycogen, were not activated in homolactate strains as they were in reference strains that produce ethanol. Finally, the anticipated increase in maximal velocity (Vmax) of glycolytic enzymes was not observed in homolactate fermentation suggesting the absence of protein synthesis that may be attributed to decreased energy availability. Essentially, anaerobic homolactate fermentation results in energy depletion, which, in turn, hinders protein synthesis, central carbon metabolism and subsequent energy generation. [source]


    Role of reserve carbohydrates in the growth dynamics of Saccharomyces cerevisiae,

    FEMS YEAST RESEARCH, Issue 8 2004
    Vincent Guillou
    Abstract The purpose of this study was to explore the role of glycogen and trehalose in the ability of Saccharomyces cerevisiae to respond to a sudden rise of the carbon flux. To this end, aerobic glucose-limited continuous cultures were challenged with a sudden increase of the dilution rate from 0.05 to 0.15 h,1. Under this condition, a rapid mobilization of glycogen and trehalose was observed which coincided with a transient burst of budding and a decrease of cell biomass. Experiments carried out with mutants defective in storage carbohydrates indicated a predominant role of glycogen in the adaptation to this perturbation. However, the real importance of trehalose in this response was veiled by the unexpected phenotypes harboured by the tps1 mutant, chosen for its inability to synthesize trehalose. First, the biomass yield of this mutant was 25% lower than that of the isogenic wild-type strain at dilution rate of 0.05 h,1, and this difference was annulled when cultures were run at a higher dilution rate of 0.15 h,1. Second, the tps1 mutant was more effective to sustain the dilution rate shift-up, apparently because it had a faster glycolytic rate and an apparent higher capacity to consume glucose with oxidative phosphorylation than the wild type. Consequently, a tps1gsy1gsy2 mutant was able to adapt to the dilution rate shift-up after a long delay, likely because the detrimental effects from the absence of glycogen was compensated for by the tps1 mutation. Third, a glg1,glg2, strain, defective in glycogen synthesis because of the lack of the glycogen initiation protein, recovered glycogen accumulation upon further deletion of TPS1. This recovery, however, required glycogen synthase. Finally, we demonstrated that the rapid breakdown of reserve carbohydrates triggered by the shift-up is merely due to changes in the concentrations of hexose-6-phosphate and UDPglucose, which are the main metabolic effectors of the rate-limiting enzymes of glycogen and trehalose pathways. [source]


    Temporal variation of energy reserves in mayfly nymphs (Hexagenia spp.) from Lake St Clair and western Lake Erie

    FRESHWATER BIOLOGY, Issue 10 2003
    J.F. Cavaletto
    Summary 1. We analysed changes in energy reserves (lipid and glycogen) and length,weight relationships of burrowing mayflies (Hexagenia spp.) in 1997,99 to compare an established population in Lake St Clair with a recovering population in western Lake Erie of the Laurentian Great Lakes. In addition, we measured changes in water temperature and potential food in both water columns and sediments. 2. Although overall mean values of lipid and glycogen levels of Hexagenia nymphs from Lake St Clair and western Lake Erie were not significantly different, there were differences in seasonal patterns between the two lakes. In Lake St Clair, levels were highest in early spring, declined throughout the year, and reached their lowest levels in fall during all 3 years of study. In contrast, levels in western Lake Erie were lower in spring, increased to a maximum in summer, then declined in fall. Seasonal patterns in length,weight relationships were similar to those for lipid and glycogen. 3. Total lipid as a percentage of dry weight did not increase with developmental stage of nymphs until just prior to metamorphosis and emergence from water. However, the major reserve lipid, triacylglycerols, increased systematically with development stage. In the final stage of development, triacylglycerols declined, probably as a result of energy consumption and its conversion to other biochemical components for metamorphosis and reproduction. 4. Indicators of potential food (algal fluorescence in the water column and chlorophyll a and chlorophyll a/phaeophytin ratio in sediments) suggest that Hexagenia in Lake St Clair have a food source that is benthic based, especially in early spring, whereas in western Lake Erie nymphs have a food source that is water column based and settles to the lake bottom during late spring and summer. [source]


    Quercitrin, a bioflavonoid improves glucose homeostasis in streptozotocin-induced diabetic tissues by altering glycolytic and gluconeogenic enzymes

    FUNDAMENTAL & CLINICAL PHARMACOLOGY, Issue 3 2010
    Ranganathan Babujanarthanam
    Abstract The present study is an investigation into the role of quercitrin on carbohydrate metabolism in normal and streptozotocin (STZ)-induced diabetic rats. Administration of STZ leads to a significant increase (P < 0.05) in fasting plasma glucose and a decrease in insulin levels. The content of glycogen is significantly decreased (P < 0.05) in liver and muscle, but increased in the kidney. The activity of hexokinase decreased whereas the activities of glucose 6-phosphatase and fructose 1,6-bisphosphatase significantly increased (P < 0.05) in the tissues. Oral administration of quercitrin (30 mg/kg) to diabetic rats for a period of 30 days resulted in significant (P < 0.05) alterations in the parameters studied but not in normal rats. A decrease of plasma glucose and increase in insulin levels were observed along with the restoration of glycogen content and the activities of carbohydrate metabolic enzymes in quercitrin-treated diabetic rats. The histopathological study of the pancreas revealed the protective role of quercitrin. There was an expansion of the islets and decreased fatty infiltrate of the islets in quercitrin treated diabetic rats. In normal rats treated with quercitrin, we could not observe any significant change in all the parameters studied. Combined, these results show that quercitrin plays a positive role in carbohydrate metabolism and antioxidant status in diabetic rats. [source]


    Disturbed hepatic carbohydrate management during high metabolic demand in medium-chain acyl,CoA dehydrogenase (MCAD),deficient mice,

    HEPATOLOGY, Issue 6 2008
    Hilde Herrema
    Medium-chain acyl,coenzyme A (CoA) dehydrogenase (MCAD) catalyzes crucial steps in mitochondrial fatty acid oxidation, a process that is of key relevance for maintenance of energy homeostasis, especially during high metabolic demand. To gain insight into the metabolic consequences of MCAD deficiency under these conditions, we compared hepatic carbohydrate metabolism in vivo in wild-type and MCAD,/, mice during fasting and during a lipopolysaccharide (LPS)-induced acute phase response (APR). MCAD,/, mice did not become more hypoglycemic on fasting or during the APR than wild-type mice did. Nevertheless, microarray analyses revealed increased hepatic peroxisome proliferator-activated receptor gamma coactivator-1, (Pgc-1,) and decreased peroxisome proliferator-activated receptor alpha (Ppar ,) and pyruvate dehydrogenase kinase 4 (Pdk4) expression in MCAD,/, mice in both conditions, suggesting altered control of hepatic glucose metabolism. Quantitative flux measurements revealed that the de novo synthesis of glucose-6-phosphate (G6P) was not affected on fasting in MCAD,/, mice. During the APR, however, this flux was significantly decreased (,20%) in MCAD,/, mice compared with wild-type mice. Remarkably, newly formed G6P was preferentially directed toward glycogen in MCAD,/, mice under both conditions. Together with diminished de novo synthesis of G6P, this led to a decreased hepatic glucose output during the APR in MCAD,/, mice; de novo synthesis of G6P and hepatic glucose output were maintained in wild-type mice under both conditions. APR-associated hypoglycemia, which was observed in wild-type mice as well as MCAD,/, mice, was mainly due to enhanced peripheral glucose uptake. Conclusion: Our data demonstrate that MCAD deficiency in mice leads to specific changes in hepatic carbohydrate management on exposure to metabolic stress. This deficiency, however, does not lead to reduced de novo synthesis of G6P during fasting alone, which may be due to the existence of compensatory mechanisms or limited rate control of MCAD in murine mitochondrial fatty acid oxidation. (HEPATOLOGY 2008.) [source]


    Human skin fibroblasts: From mesodermal to hepatocyte-like differentiation,

    HEPATOLOGY, Issue 5 2007
    Philippe A. Lysy
    The phenotypic homology of fibroblasts and mesenchymal stem cells (MSCs) has been recently described. Our study investigated the in vitro potential of human skin fibroblasts to differentiate into mesodermal (osteocyte and adipocyte) and endodermal (hepatocyte) cell lineages by comparison with human bone marrow (hBM) MSCs. The endodermal potential of fibroblasts was then explored in vivo in a mouse model of liver injury. Fibroblasts were able to acquire osteocyte and adipocyte phenotypes as assessed by cytochemistry and gene expression analyses. After exposure to a specific differentiation cocktail, these cells presented hepatocyte-like morphology and acquired liver-specific markers on protein and gene expression levels. Furthermore, these fibroblast-derived hepatocyte-like cells (FDHLCs) displayed the ability to store glycogen and synthesize small amounts of urea. By gene expression analysis, we observed that fibroblasts remained in a mesenchymal-epithelial transition state after hepatocyte differentiation. Moreover, FDHLCs lost their hepatocyte-like phenotype after dedifferentiation. In vivo, human fibroblasts infused directly into the liver of hepatectomized severe combined immunodeficient (SCID) mice engrafted in situ and expressed hepatocyte markers (albumin, alpha-fetoprotein, and cytokeratin 18) together with the mesodermal marker fibronectin. Despite lower liver-specific marker expression, the in vitro and in vivo differentiation profile of fibroblasts was comparable to that of mesenchymal-derived hepatocyte-like cells (MDHLCs). In conclusion, our work demonstrates that human skin fibroblasts are able to display mesodermal and endodermal differentiation capacities and provides arguments that these cells share MSCs features both on the phenotypic and functional levels. (HEPATOLOGY 2007;46:1574,1585.) [source]


    ,-Glutamyltranspeptidase,deficient knockout mice as a model to study the relationship between glutathione status, mitochondrial function, and cellular function

    HEPATOLOGY, Issue 4 2000
    Yvonne Will
    ,-Glutamyltranspeptidase (GGT)-deficient mice (GGT,/,) display chronic glutathione (GSH) deficiency, growth retardation, and die at a young age (<20 weeks). Using livers from these mice, we investigated the relationship between GSH content, especially mitochondrial, and mitochondrial and cellular function. We found that the GSH content of isolated liver mitochondria was diminished by ,50% in GGT,/, mice when compared with wild-type mice. Respiratory control ratios (RCRs) of GGT,/, mice liver mitochondria were ,60% those of wild-type mice primarily as a result of impaired state 3 respiration. Mitochondrial adenine nucleotide content was decreased by ,40% in mitochondria obtained from GGT,/, mice. We observed a strong correlation between mitochondrial GSH content and RCRs. Even moderate decreases (<50%) correlated with adverse effects with respect to respiration. Electron microscopy revealed that livers from GGT,/, knockout mice were deprived of fat and glycogen, and swollen mitochondria were observed in animals that were severely deprived of GSH. Thus, GGT,/, mice exhibit a loss of GSH homeostasis and impaired oxidative phosphorylation, which may be related to the rate of adenosine triphosphate (ATP) formation and subsequently leads to progressive liver injury, which characterizes the diseased state. We also found that supplementation of GGT,/, mice with N -acetylcysteine (NAC) partially restored liver GSH, but fully restored mitochondrial GSH and respiratory function. Electron microscopy revealed that the livers of NAC-supplemented GGT,/, mice contained fat and glycogen; however, slightly enlarged mitochondria were found in some livers. NAC supplementation did not have any beneficial effect on the parameters examined in wild-type mice. [source]