scholarly journals Regulation of N-glycolylneuraminic acid biosynthesis in developing pig small intestine

2003 ◽  
Vol 370 (2) ◽  
pp. 601-607 ◽  
Author(s):  
Yanina N. MALYKH ◽  
Timothy P. KING ◽  
Elizabeth LOGAN ◽  
Denise KELLY ◽  
Roland SCHAUER ◽  
...  
Keyword(s):  
Small Intestine ◽  
Sialic Acid ◽  
Post Partum ◽  
Acid Biosynthesis ◽  
Acetylneuraminic Acid ◽  
Total Sialic Acid ◽  
Key Factor ◽  
Developmental Phases ◽  
Cytosolic Factors

N-Glycolylneuraminic acid (Neu5Gc), an abundant sialic acid in animal glycoconjugates, is formed by the enzyme CMP-N-acetylneuraminic acid (CMP-Neu5Ac) hydroxylase. The amount of Neu5Gc relative to other sialic acids is highly dependent on the species, tissue and developmental stage. Although the activity of the hydroxylase is a key factor in controlling Neu5Gc incorporation in adult animals, little is known about the regulation of hydroxylase expression and the role of this enzyme in determining changes in Neu5Gc during development. Using pig small intestine as a model system, the appearance of total sialic acid and the regulation of Neu5Gc biosynthesis during development were studied in various regions of this tissue. The amount of total sialic acid and Neu5Gc declined markedly in 2 weeks after birth. Although in subsequent developmental phases there were no positional differences in total sialic acid, a significant proximal-to-distal increase in Neu5Gc was detected. In all cases, a good correlation between the amount of Neu5Gc, the activity of the hydroxylase and the level of hydroxylase mRNA was observed. However, Western-blot analysis revealed considerable accumulation of less active enzyme in the post partum period, which persisted until adulthood. No evidence for cytosolic factors influencing the hydroxylase activity or for the formation of truncated enzyme was found, raising the possibility that other regulatory mechanisms are involved. The relevance of these results in the formation of Neu5Gc as a receptor for certain pig enteric pathogens is also discussed.

Regulation and pathophysiological implications of UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) as the key enzyme of sialic acid biosynthesis

2009 ◽  
Vol 390 (7) ◽  
Author(s):  
Stefan O. Reinke ◽  
Gerhard Lehmer ◽  
Stephan Hinderlich ◽  
Werner Reutter
Keyword(s):  
Sialic Acid ◽  
Crucial Role ◽  
Feedback Inhibition ◽  
Acid Biosynthesis ◽  
Knock Out ◽  
Acetylneuraminic Acid ◽  
Kinase C ◽  
Key Enzyme ◽  
Hereditary Inclusion Body Myopathy

AbstractThe key enzyme for the biosynthesis ofN-acetylneuraminic acid, from which all other sialic acids are formed, is the bifunctional enzyme UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). GNE is a highly conserved protein found throughout the animal kingdom. Its highest expression is seen in the liver and placenta. GNE is regulated by a variety of biochemical means, including tetramerization promoted by the substrate UDP-GlcNAc, phosphorylation by protein kinase C and feedback inhibition by CMP-Neu5Ac, which is defect in the human disease sialuria. GNE knock-out in mice leads to embryonic lethality, emphasizing the crucial role of this key enzyme for sialic acid biosynthesis. The metabolic capacity to synthesize sialic acid and CMP-sialic acid upon ManNAc loads is amazingly high. An additional characteristic of GNE is its interaction with proteins involved in the regulation of development, which might play a crucial role in the hereditary inclusion body myopathy. Due to the importance of increased concentrations of tumor-surface sialic acid, first attempts to find inhibitors of GNE have been successful.

scholarly journals Intestinal neuraminidase activity of suckling rats and other mammals. Relationship to the sialic acid content of milk

1978 ◽  
Vol 170 (2) ◽  
pp. 407-413 ◽  
Author(s):  
J J Dickson ◽  
M Messer
Keyword(s):  
Small Intestine ◽  
Sialic Acid ◽  
Gastric Mucosa ◽  
Acid Content ◽  
Significant Positive Correlation ◽  
Post Partum ◽  
Sialic Acid Content ◽  
Neuraminidase Activity ◽  
Stage Of Lactation ◽  
Old Rats

1. The neuraminidase activity of homogenates of the mucosa of the middle and distal thirds of the small intestine of rats increased about 5-fold between birth and 4 to 8 days of age, and then gradually declined to the much lower adult activity by 24 days. No comparable changes occurred in the proximal third. 2. In 8-day-old rats, the neuraminidase activity of the middle and distal thirds of the small intestine was about 10 times greater than that of the proximal third, 20 times greater than that of the colon and at least 100 times greater than that of the liver, brain, gastric mucosa or pancreas. 3. In all other species investigated (mice, rabbits, cats and guinea pigs), the neuraminidase activity of the middle and distal thirds of the small intestine was greater in suckling animals than in adults. 4. The sialic acid content of rat milk increased about 2-fold between birth and 8 days post partum and then declined. 5. There was a highly significant positive correlation between the intestinal neuraminidase activity of suckling animals of various species and ages and the sialic acid content of milk obtained from the corresponding species and stage of lactation. 6. It is suggested that the intestinal neuraminidase of suckling mammals functions primarily to remove sialic acid from various components of milk, thus providing sialic acid for the synthesis of sialoglycoproteins and gangliosides by the young.

scholarly journals Regulation of colominic acid biosynthesis by temperature: Role of cytidine 5′-monophosphateN-acetylneuraminic acid synthetase

FEBS Letters ◽  
1989 ◽  
Vol 250 (2) ◽  
pp. 429-432 ◽  
Author(s):  
Camino González-Clemente ◽  
José M. Luengo ◽  
Leandro B. Rodríguez-Aparicio ◽  
Angel Reglero
Keyword(s):  
Acid Biosynthesis ◽  
Acetylneuraminic Acid ◽  
Colominic Acid

scholarly journals Sialic Acid Species as a Determinant of the Host Range of Influenza A Viruses

2000 ◽  
Vol 74 (24) ◽  
pp. 11825-11831 ◽  
Author(s):  
Yasuo Suzuki ◽  
Toshihiro Ito ◽  
Takashi Suzuki ◽  
Robert E. Holland ◽  
Thomas M. Chambers ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Viral Replication ◽  
Influenza A ◽  
Lectin Binding ◽  
Influenza Viruses ◽  
Influenza A Viruses ◽  
Acetylneuraminic Acid ◽  
Human Viruses ◽  
Immunohistochemical Analyses

ABSTRACT The distribution of sialic acid (SA) species varies among animal species, but the biological role of this variation is largely unknown. Influenza viruses differ in their ability to recognize SA-galactose (Gal) linkages, depending on the animal hosts from which they are isolated. For example, human viruses preferentially recognize SA linked to Gal by the α2,6(SAα2,6Gal) linkage, while equine viruses favor SAα2,3Gal. However, whether a difference in relative abundance of specific SA species (N-acetylneuraminic acid [NeuAc] andN-glycolylneuraminic acid [NeuGc]) among different animals affects the replicative potential of influenza viruses is uncertain. We therefore examined the requirement for the hemagglutinin (HA) for support of viral replication in horses, using viruses whose HAs differ in receptor specificity. A virus with an HA recognizing NeuAcα2,6Gal but not NeuAcα2,3Gal or NeuGcα2,3Gal failed to replicate in horses, while one with an HA recognizing the NeuGcα2,3Gal moiety replicated in horses. Furthermore, biochemical and immunohistochemical analyses and a lectin-binding assay demonstrated the abundance of the NeuGcα2,3Gal moiety in epithelial cells of horse trachea, indicating that recognition of this moiety is critical for viral replication in horses. Thus, these results provide evidence of a biological effect of different SA species in different animals.

scholarly journals THE LYSOSOME PERIPHERY: BIOCHEMICAL AND ELECTROKINETIC PROPERTIES OF THE TRITOSOME SURFACE

1974 ◽  
Vol 60 (3) ◽  
pp. 764-773 ◽  
Author(s):  
Douglas M. Gersten ◽  
Thomas W. Kimmerer ◽  
H. Bruce Bosmann
Keyword(s):  
Sialic Acid ◽  
Electrophoretic Mobility ◽  
Membrane Fraction ◽  
Osmotic Shock ◽  
Particle Surface ◽  
Gas Liquid Chromatography ◽  
Present System ◽  
Acid Hydrolases ◽  
Acetylneuraminic Acid ◽  
Total Sialic Acid

Normal rat liver lysosomes were isolated by the technique of loading with Triton WR-1339. Purity of the preparation was monitored with marker enzymes; a high enrichment in acid hydrolases was obtained in the tritosome fraction. In 0.0145 M NaCl, 4.5% sorbitol, 0.6 mM NaHCO3, pH 7.2 at 25°C the tritosomes had an electrophoretic mobility of -1.77 ± 0.02 µm/s/V/cm, a zeta potential of 23.2 mV, a surface charge of 1970 esu/cm2, and 33,000 electrons per particle surface assuming a tritosome diameter of 5 x 10-7 m. Treatment of the tritosomes with 50 µg neuraminidase/mg tritosome protein lowered the electrophoretic mobility of the tritosome to -1.23 ± 0.02 µm/s/V/cm under the same conditions and caused the release of 2.01 µg sialic acid/mg tritosome protein. Treatment of the tritosomes with hyaluronidase did not affect their electrophoretic mobility, while trypsin treatment elevated the net negative electrophoretic mobility of the tritosomes. Tritosome electrophoretic mobilities indicated a homogeneous tritosome population and varied greatly with ionic strength of the suspending media. pH vs. electrophoretic mobility curves indicated the tritosome periphery to contain an acid-dissociable group which likely represents the carboxyl group of N-acetylneuraminic acid; this was not conclusively proven, however, since the tritosomes lysed below a pH of 4 in the present system. Total tritosome carbohydrate (anthrone-positive material as glucose equivalents) was 0.19 mg/mg tritosome protein while total sialic acid was 3.8 µg (11.4 nmol)/mg tritosome protein. A tritosome "membrane" fraction was prepared by osmotic shock, homogenization, and sedimentation. Approximately 25% of the total tritosome protein was present in this fraction. Analysis by gas-liquid chromatography and amino acid analyzer showed the following carbohydrate composition of the tritosome membrane fraction (in microgram per milligram tritosome membrane protein): N-acetylneuraminic acid, 14.8 ± 3; glucosamine, 24 ± 3; galactosamine, 10 ± 2; glucose, 21 ± 2; galactose, 26 ± 2; mannose, 31 ± 5; fucose, 7 ± 1; xylose, 0; and arabinose, 0. The results indicate that the tritosome periphery is characterized by external terminal sialic acid residues and an extensive complement of glycoconjugates. Essentially all the tritosome N-acetylneuraminic acid is located in the membrane and about 53% of it is neuraminidase susceptible.

scholarly journals The Capability of Catabolic Utilization of N-Acetylneuraminic Acid, a Sialic Acid, Is Essential for Vibrio vulnificus Pathogenesis

2009 ◽  
Vol 77 (8) ◽  
pp. 3209-3217 ◽  
Author(s):  
Hee Gon Jeong ◽  
Man Hwan Oh ◽  
Byoung Sik Kim ◽  
Min Young Lee ◽  
Ho Jae Han ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Epithelial Cells ◽  
Vibrio Vulnificus ◽  
Gene Encoding ◽  
Acetylneuraminic Acid ◽  
Enteropathogenic Bacteria ◽  
Mouse Intestine

ABSTRACT N-acetylneuraminic acid (Neu5Ac, sialic acid) could provide a good substrate for enteropathogenic bacteria in the intestine, when the bacteria invade and colonize in human gut. In order to analyze the role of Neu5Ac catabolism in Vibrio vulnificus pathogenesis, a mutant with disruption of the nanA gene encoding Neu5Ac lyase was constructed by allelic exchanges. The nanA mutant was not able to utilize Neu5Ac as a sole carbon source and revealed an altered colony morphotype with reduced opacity in the presence of Neu5Ac. Compared to the wild type, the nanA mutant exhibited a low level of cytotoxicity toward INT-407 epithelial cells in vitro and reduced virulence in a mouse model. The disruption of nanA also resulted in a substantial decrease in histopathological damage in jejunum and colon tissues from the mouse intestine. These results indicated that NanA plays an important role in V. vulnificus pathogenesis. In addition, the nanA mutant was significantly diminished in growth with and adherence to INT-407 epithelial cells in vitro, and was defective for intestinal colonization, reflecting the impaired ability of the mutant to grow and survive with, persist in, and adhere to the intestine in vivo. Consequently, the combined results suggest that NanA and the capability of catabolic utilization of Neu5Ac contribute to V. vulnificus virulence by ensuring growth, adhesion, and survival during infection.

Sialoglycoproteins and sialic acids ofPlasmodium knowlesischizont-infected erythrocytes and normal rhesus monkey erythrocytes

Parasitology ◽  
1986 ◽  
Vol 92 (3) ◽  
pp. 527-543 ◽  
Author(s):  
R. J. Howard ◽  
G. Reuter ◽  
J. W. Barnwell ◽  
R. Schauer
Keyword(s):  
Sialic Acid ◽  
Rhesus Monkey ◽  
Acid Content ◽  
Sialic Acids ◽  
Galactose Oxidase ◽  
Parasite Development ◽  
Sialic Acid Content ◽  
Acetylneuraminic Acid ◽  
Total Sialic Acid ◽  
Significant Difference

SUMMARYThe effects of malaria infection on RBC sialic acids and sialoglycoproteins were studied with asexual blood-stage infections ofPlasmodium knowlesiin rhesus monkeys. Glycoprotein radio-isotope labelling methods were used to compare the sialoglycoproteins of normal RBC andP. knowlesischizont-infected RBC (SI-RBC). Tritiation of glycoproteins from SI-RBC with the standard sialidase + galactose oxidase/NaB3H4method or standard periodate/NaB3H4method was significantly decreased when compared to normal RBC. However, tritium uptake into glycoproteins was normal when SI-RBC were treated with 5-fold higher concentrations of both enzymes in the first labelling method, or with a 5-fold increase in the molar ratio of periodate to sialic acid in the second method. The mobility of tritiated host cell glycoproteins on SDS–polyacrylamide gels was identical for SI-RBC and normal RBC. New bands, possibly glycoproteins, of 230, 160, 90, 52, and 30 kDa were detected after labelling SI-RBC by the modified periodate/NaB3H4method. Sialic acid analysis of normal rhesus monkey RBC (62μg/1010RBC) revealed that 46% of the total sialic acid wasN-glycolylneuraminic acid, 33% wasN-acetyl-9-O-acetylneuraminic acid, and the remainderN-acetylneuraminic acid. SI-RBC collected either directly from infected monkeys or afterin vitroculture of ring-infected RBC in horse serum, had increased total sialic acid (126 or 115μg/1010RBC, respectively). The sialic acid content of infected RBC must increase during parasite development since RBC infected with ring-stageP. knowlesihad the same content as normal RBC. There was no significant difference in the ratio of the three sialic acids of SI-RBC and normal RBC. In contrast, the uninfected RBC from infected blood of different monkeys showed marked variation in sialic acid composition and generally had a lower sialic acid content than normal RBC.

scholarly journals Radioimmunochemical evidence for a role of carbohydrate in antigenic determinant(s) on human liver α-L-fucosidase

1984 ◽  
Vol 223 (2) ◽  
pp. 293-298 ◽  
Author(s):  
J A Alhadeff ◽  
G L Andrews-Smith
Keyword(s):  
Sialic Acid ◽  
Antigenic Determinant ◽  
Human Liver ◽  
Competitive Ability ◽  
Sialic Acids ◽  
Acetylneuraminic Acid ◽  
Colominic Acid ◽  
Sugar Derivatives ◽  
Radioimmunoassay Method

A competitive-binding radioimmunoassay method was employed to investigate the role of carbohydrate in antigenic determinant(s) of human liver alpha-L-fucosidase. Competition curves were used to quantify the concentrations of competitors needed to cause 30% inhibition of the precipitation of 125I-labelled alpha-L-fucosidase. The isoelectric forms of alpha-L-fucosidase, which are related by sialic acid residues, were separated preparatively and used as competitors in the radioimmunoassay. A pattern of increasing effectiveness as competitors with increasing acidity of the forms was found, suggesting that sialic acid may be involved in the antigenic determinant(s) of alpha-L-fucosidase. Specificity was exhibited when sugar and sugar derivatives were used as competitors in the radioimmunoassay: a 51-fold range of competitive ability was found, and sialic acids (N-acetylneuraminic acid and N-glycollylneuraminic acid) and colominic acid (a polymer of N-acetylneuraminic acid) were the best competitors. The results of our studies suggest that carbohydrate contributes to antigenic determinant(s) of alpha-L-fucosidase and that sialic acid is probably the major sugar involved.

scholarly journals The Protective Role Of Resveratrol On Serum Total Sialic Acid And Lipid-Bound Sialic Acid In Female Rats With Chronic Fluorosis

2016 ◽  
Vol 21 (4) ◽  
pp. 168-172 ◽  
Author(s):  
Gökhan Oto ◽  
Suat Ekin ◽  
Hulya Özdemir ◽  
Mehmet Bulduk ◽  
Hasan Uyar ◽  
...  
Keyword(s):  
Sialic Acid ◽  
Protective Role ◽  
Female Rats ◽  
Total Sialic Acid ◽  
Chronic Fluorosis

scholarly journals Sialic Acid-Mediated Gene Expression in Streptococcus pneumoniae and Role of NanR as a Transcriptional Activator of thenanGene Cluster

2015 ◽  
Vol 81 (9) ◽  
pp. 3121-3131 ◽  
Author(s):  
Muhammad Afzal ◽  
Sulman Shafeeq ◽  
Hifza Ahmed ◽  
Oscar P. Kuipers
Keyword(s):  
Streptococcus Pneumoniae ◽  
Sialic Acid ◽  
Gene Cluster ◽  
Microarray Analysis ◽  
Transcriptional Activator ◽  
Transcriptomic Response ◽  
Content Type ◽  
Acetylneuraminic Acid ◽  
Elevated Expression

ABSTRACTIn this study, we investigated the transcriptomic response ofStreptococcus pneumoniaeD39 to sialic acid (N-acetylneuraminic acid [Neu5Ac]). Transcriptome comparison of wild-type D39 grown in M17 medium with and without sialic acid revealed the elevated expression of various genes and operons, including thenangene cluster (nanoperon I andnanAgene). Our microarray analysis and promoter-lacZfusion studies showed that the transcriptional regulator NanR acts as a transcriptional activator ofnanoperon I and thenanAgene in the presence of sialic acid. The putative regulatory site of NanR in the promoter region ofnanoperon I is predicted and confirmed by promoter truncation experiments. Furthermore, the role of CcpA in the regulation of thenangene cluster is demonstrated through microarray analysis and promoter-lacZfusion studies, suggesting that in the presence of sialic acid and glucose, CcpA represses the expression ofnanoperon I while the expression of thenanAgene is CcpA independent.

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