Abstract
Recent studies have shown a relationship between the level of the sialic acid (Sia), N-glycolylneuraminic acid (Neu5Gc) in red meat and its risk in cancer, cardiovascular and inflammatory diseases. Unresolved is the Sia concentration in different organs of piglets during development. Our aim was to determine the level of free and conjugated forms of Neu5Gc, N-acetylneuraminic acid (Neu5Ac) and ketodeoxynonulsonic acid (Kdn) in fresh and cooked spleen, kidney, lung, heart, liver, and skeletal muscle from 3-days-old (n = 4–8), 38-days-old (n = 10) and adult piglets (n = 4) by LC-MS/MS. Our findings show: (1) Lung tissue from 3 days-old piglets contained the highest level of total Sia (14.6 μmol/g protein) compared with other organs or age groups; (2) Unexpectedly, Neu5Gc was the major Sia in spleen (67–79 %) and adult lung (36–49 %) while free Kdn was the major Sia in skeletal muscle. Conjugated Neu5Ac was the highest Sia in other organs (61–84 %); (3) Skeletal muscle contained the lowest concentration of Neu5Gc in fresh and cooked meat; (4) Kdn accounted for <5 % of the total Sia in most organs; (5) During development, the total Sia concentration showed a 44–79 % decrease in all organs; (6) In adult piglets, the high to low rank order of total Sia was lung, heart, spleen, kidney, liver and skeletal muscle. In conclusion, the high level of Neu5Gc in all organs compared to skeletal muscle is a potential risk factor suggesting that dietary consumption of organ meats should be discouraged in favor of muscle to protect against cancer, cardiovascular and other inflammatory diseases.
Similar content being viewed by others
Abbreviations
- Sia:
-
Sialic acid
- Neu5Ac:
-
N-acetylneuraminic acid
- Neu5Gc:
-
N-glycolylneuraminic acid
- Kdn:
-
2-keto-3-deoxy-D-glycero- D-galacto-nononic acid (Ketodeoxynonulosonic acid)
- LC-MS/MS:
-
Liquid chromatography-tandem mass spectrometry
References
Havelaar A.C., Mancini G.M., Beerens C.E., Souren R.M., Verheijen F.W.: Purification of the lysosomal sialic acid transporter. Functional characteristics of a monocarboxylate transporter. J. Biol. Chem. 273(51), 34568–34574 (1998)
Schauer R.: Achievements and challenges of sialic acid research. Glycoconj. J. 17(7–9), 485–499 (2000)
Schauer R.: Sialic acids as regulators of molecular and cellular interactions. Curr. Opin. Struc. Biol. 19(5), 507–514 (2009). doi:10.1016/j.sbi.2009.06.003
Troy II F.A.: Polysialylation: from bacteria to brains. Glycobiology. 2(1), 5–23 (1992)
Chen X., Varki A.: Advances in the Biology and Chemistry of Sialic Acids. ACS Chem. Biol. 5(2), 163–176 (2010). doi:10.1021/cb900266r
Sato C., Kitajima K.: Disialic, oligosialic and polysialic acids: distribution, functions and related disease. J. Biochem. 154(2), 115–136 (2013). doi:10.1093/jb/mvt057
Wang B.: Molecular mechanism underlying sialic acid as an essential nutrient for brain development and cognition. Adv. Nutr. 3(3), 465S–472S (2012). doi:10.3945/an.112.001875
Diaz S.L., Padler-Karavani V., Ghaderi D., Hurtado-Ziola N., Yu H., Chen X., Brinkman-Van der Linden E.C.M., Varki A., Varki N.M.: Sensitive and Specific Detection of the Non-Human Sialic Acid N-Glycolylneuraminic Acid In Human Tissues and Biotherapeutic Products. PLoS ONE. 4(1), e4241 (2009). doi:10.1371/journal.pone.0004241
Inoue S., Lin S.L., Chang T., Wu S.H., Yao C.W., Chu T.Y., Troy 2nd F.A., Inoue Y.: Identification of free deaminated sialic acid (2-keto-3-deoxy-D-glycero-D-galacto- nononic acid) in human red blood cells and its elevated expression in fetal cord red blood cells and ovarian cancer cells. J. Biol. Chem. 273(42), 27199–27204 (1998)
Wang F., Xie B., Wang B., Troy 2nd F.A.: LC-MS/MS Glycomic Analyses of Free and Conjugated Forms of the Sialic Acids, Neu5Ac, Neu5Gc and Kdn in Human Throat Cancers. Glycobiology. (2015). doi:10.1093/glycob/cwv051
Morimoto N., Nakano M., Kinoshita M., Kawabata A., Morita M., Oda Y., Kuroda R., Kakehi K.: Specific distribution of sialic acids in animal tissues as examined by LC-ESI-MS after derivatization with 1, 2-diamino-4, 5-methylenedioxybenzene. Anal. Chem. 73(22), 5422–5428 (2001)
van der Ham M., Prinsen B.H.C.M.T., Huijmans J.G.M., Abeling N.G.G.M., Dorland B., Berger R., de Koning T.J., Velden M.G.M.D.S.V.: Quantification of free and total sialic acid excretion by LC-MS/MS. J. Chromatogr. B. 848(2), 251–257 (2007). doi:10.1016/j.jchromb.2006.10.066
Rajan R., Sheth A.R., Rao S.S.: Sialic-Acid, Sialyltransferase and Neuraminidase Levels in Maternal Plasma. Urine and Lymphocytes during Pregnancy and Postpartum Period - a Longitudinal-Study in Women. Eur. J. Obstet. Gyn R B. 16(1), 37–46 (1983). doi:10.1016/0028-2243(83)90218-6
Karunanithi, D., Radhakrishna, A., Biju, V.: Quantitative determination of sialic acid in Indian milk and milk products. International Journal of Applied Biology and P (2013)
Spichtig V., Michaud J., Austin S.: Determination of sialic acids in milks and milk-based products. Anal. Biochem. 405(1), 28–40 (2010). doi:10.1016/j.ab.2010.06.010
ten Bruggencate S.J.M., Bovee-Oudenhoven I.M.J., Feitsma A.L., van Hoffen E., Schoterman M.H.C.: Functional role and mechanisms of sialyllactose and other sialylated milk oligosaccharides. Nutr. Rev. 72(6), 377–389 (2014). doi:10.1111/nure.12106
Steenbergen S.M., Vimr E.R.: Functional Relationships of the Sialyltransferases Involved in Expression of the Polysialic Acid Capsules of Escherichia coli K1 and K92 and Neisseria meningitidis Groups B or C. J. Biol. Chem. 278(17), 15349–15359 (2003)
Brunngraber E.G., Brown B.D., Chang I.: Glycoproteins in subacute sclerosing leukoencephalitis: isolation and carbohydrate composition of glycopeptides from human brain. J. Neuropath. Experim. neurol. 30(3), 525–535 (1971)
Wang B., Miller J.B., McNeil Y., McVeagh P.: Sialic acid concentration of brain gangliosides: Variation among eight mammalian species. Comp Biochem Phys A. 119(1), 435–439 (1998). doi:10.1016/S1095-6433(97)00445-5
Stasche R., Hinderlich S., Weise C., Effertz K., Lucka L., Moormann P., Reutter W.: A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver - Molecular cloning and functional expression of UDP-N-acetyl-glucosamine 2-epimerase/N-acetylmannosamine kinase. J. Biol. Chem. 272(39), 24319–24324 (1997). doi:10.1074/jbc.272.39.24319
Hinderlich S., Stasche R., Zeitler R., Reutter W.: A bifunctional enzyme catalyzes the first two steps in N-acetylneuraminic acid biosynthesis of rat liver - Purification and characterization of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase. J. Biol. Chem. 272(39), 24313–24318 (1997). doi:10.1074/jbc.272.39.24313
Varki A.: Sialic acids in human health and disease. Trends Mol. Med. 14(8), 351–360 (2008). doi:10.1016/j.molmed.2008.06.002
Wang B.: Sialic acid is an essential nutrient for brain development and cognition. Ann Rev. Nutr. 29, 177–222 (2009). doi:10.1146/annurev.nutr.28.061807.155515
Troy F.A.: Sialobiology and the Polysialic Acid Glycotope Occurrence, Structure, Function, Synthesis, and Glycopathology. In: Rosenberg A. (ed.) Biology of the Sialic Acids, pp. 95–144. Springer US, Boston, MA (1995)
Drake P.M., Nathan J.K., Stock C.M., Chang P.V., Muench M.O., Nakata D., Reader J.R., Gip P., Golden K.P., Weinhold B., Gerardy-Schanh R., Troy II F.A., Bertozzi C.R.: Polysialic acid, a glycan with highly restricted expression, is found on human and murine leukocytes and modulates immune responses. J. Immunol. 181(10), 6850–6858 (2008)
Davies L.R., Varki A.: Why Is N-Glycolylneuraminic Acid Rare in the Vertebrate Brain? Top. Curr. Chem. 366, 31–54 (2015). doi:10.1007/128_2013_419
Sinha R., Graubard B.I., Cross A.J., Leitzmann M.F., Schatzkin A.: Higher Red Meat Intake May Be a Marker of Risk. Not a Risk Factor Itself Reply. Arch Intern Med. 169(16), 1539–1539 (2009)
Samraj A.N., Pearce O.M., Laubli H., Crittenden A.N., Bergfeld A.K., Banda K., Gregg C.J., Bingman A.E., Secrest P., Diaz S.L., Varki N.M., Varki A.: A red meat-derived glycan promotes inflammation and cancer progression. Proc.Natl. Acad. Sci. U. S. A. 112(2), 542–547 (2015). doi:10.1073/pnas.1417508112
Hedlund M., Tangvoranuntakul P., Takematsu H., Long J.M., Housley G.D., Kozutsumi Y., Suzuki A., Wynshaw-Boris A., Ryan A.F., Gallo R.L., Varki N., Varki A.: N-glycolylneuraminic acid deficiency in mice: implications for human biology and evolution. Mol. Cell. Biol. 27(12), 4340–4346 (2007). doi:10.1128/MCB.00379-07
Tangvoranuntakul P., Gagneux P., Diaz S., Bardor M., Varki N., Varki A., Muchmore E.: Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. Proc.Natl. Acad. Sci. U. S. A. 100(21), 12045–12050 (2003). doi:10.1073/pnas.2131556100
Cho E., Chen W.Y., Hunter D.J., Stampfer M.J., Colditz G.A., Hankinson S.E., Willett W.C.: Red meat intake and risk of breast cancer among premenopausal women. Arch. Intern. Med. 166(20), 2253–2259 (2006)
Taylor V.H., Misra M., Mukherjee S.D.: Is red meat intake a risk factor for breast cancer among premenopausal women? Breast Cancer Res. Treat. 117(1), 1–8 (2009)
Larsen J.: Meat consumption in China now double that in the United States. Earth Policy Institute. 24, (2012)
Williams P.: Nutritional composition of red meat. Nutr. Diet. 64, S113–S119 (2007). doi:10.1111/j.1747-0080.2007.00197.x
Jiang Z., Rothschild M.F.: Swine genome science comes of age. Int. J. Biol. Sci. 3(3), 129–131 (2007)
Kwon D.-N., Chang B.-S., Kim J.-H.: Gene expression and pathway analysis of effects of the CMAH deactivation on mouse lung, kidney and heart. PLoS One. 9(9), e107559 (2014)
Cheng Y.: Chinese dietary reference intake. 2013 revision introduction. Acta Nutrimenta Sinica. 36, 313–315 (2014)
Chen Y., Pan L.L., Liu N., Troy F.A., Wang B.: LC-MS/MS quantification of N-acetylneuraminic acid, N-glycolylneuraminic acid and ketodeoxynonulosonic acid levels in the urine and potential relationship with dietary sialic acid intake and disease in 3- to 5-year-old children. Brit J Nutr. 111(2), 332–341 (2014). doi:10.1017/S0007114513002468
Acknowledgments
This study was funded by research grants from the School of Medicine, Xiamen University.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
The authors declare that they have no conflicts of interest.
Ethical approval
This article does not contain any studies with human participants performed by any of the authors.
Rights and permissions
About this article
Cite this article
Ji, S., Wang, F., Chen, Y. et al. Developmental changes in the level of free and conjugated sialic acids, Neu5Ac, Neu5Gc and KDN in different organs of pig: a LC-MS/MS quantitative analyses. Glycoconj J 34, 21–30 (2017). https://doi.org/10.1007/s10719-016-9724-9
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10719-016-9724-9