Cytidine Monophospho-N-Acetylneuraminic Acid Hydroxylase (CMAH)

Reference work entry


Sialic acids are a family of more than 50 naturally occurring acidic nine-carbon backbone monosaccharides. The predominant sialic acids in mammals are N-acetylneuraminic acid (Neu5Ac) and N-glycolylneuraminic acid (Neu5Gc), which commonly occupy the terminal positions of various glycan chains (Varki and Schauer 2009). The only known biosynthetic pathway for generation of Neu5Gc takes place in the cytosol and is catalyzed by the cytidine monophospho-N-acetylneuraminic acid hydroxylase (Cmah). The Cmah enzyme acts only at the level of activated sugars and catalyzes the conversion of the precursor molecule CMP-Neu5Ac to CMP-Neu5Gc involving a complex mechanism with cofactors NADH, cytochrome b5, b5 reductase, iron, and molecular oxygen (Shaw and Schauer 1988; Muchmore et al. 1989; Kozutsumi et al. 1990; Shaw et al. 1992, 1994; Kawano et al. 1993, 1995; Schneckenburger et al. 1994; Takematsu et al. 1994; Schlenzka et al. 1996). The Cmah enzyme is conserved among animals of the deuterostome lineage (vertebrates and “higher” invertebrates), but no homologous enzymes are known in any other eukaryotic taxa (Varki 2009). Only distantly related bacterial and plant hydroxylases were predicted to have some degree of structural similarity to Cmah (Schmidt and Shaw 2001). Interestingly, N-glycolyl groups are very rare in nature. Besides the Cmah enzyme, only one bacterial enzyme is known to be capable of generating N-glycolyl groups in the form of N-glycolylmuramic acid in mycobacteria (Raymond et al. 2005). Notably, the responsible gene namH shows distant homology to CMAH and acts on a nucleotide sugar (UDP-N-acetylmuramic acid) as well.


Sialic Acid Duchenne Muscular Dystrophy Duchenne Muscular Dystrophy Polysialic Acid Acid Hydroxylase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Supported by NIH grant R01GM32373.


  1. Angata T, Varki A (2002) Chemical diversity in the sialic acids and related alpha-keto acids: an evolutionary perspective. Chem Rev 102:439–469PubMedCrossRefGoogle Scholar
  2. Banda K, Gregg CJ, Chow R, Varki NM, Varki A (2012) Metabolism of vertebrate amino sugars with N-Glycolyl groups:mechanisms underlying gastrointestinal incorporation of the non-human sialic acid xeno-autoantigen N-glycolylneuraminic acid. J Biol Chem 287:28852–28864PubMedCrossRefGoogle Scholar
  3. Bardor M, Nguyen DH, Diaz S, Varki A (2005) Mechanism of uptake and incorporation of the non-human sialic acid N-glycolylneuraminic acid into human cells. J Biol Chem 280:4228–4237PubMedCrossRefGoogle Scholar
  4. Basnet NB, Ide K, Tahara H, Tanaka Y, Ohdan H (2010) Deficiency of N-glycolylneuraminic acid and Galalpha1-3Galbeta1-4GlcNAc epitopes in xenogeneic cells attenuates cytotoxicity of human natural antibodies. Xenotransplantation 17:440–448PubMedCrossRefGoogle Scholar
  5. Bergfeld AK, Pearce OM, Diaz SL, Lawrence R, Vocadlo DJ, Choudhury B, Esko JD, Varki A (2012a) Metabolism of vertebrate amino sugars with N-Glycolyl groups: incorporation of N-glycolylhexosamines into mammalian glycans by feeding N-glycolylgalactosamine. J Biol Chem 287:28898–28916PubMedCrossRefGoogle Scholar
  6. Bergfeld AK, Pearce OM, Diaz SL, Pham T, Varki A (2012b) Metabolism of vertebrate amino sugars with N-Glycolyl groups: elucidating the intracellular fate of the non-human sialic acid N-glycolylneuraminic acid. J Biol Chem 287:28865–28881PubMedCrossRefGoogle Scholar
  7. Bergwerff AA, Hulleman SHD, Kamerling JP, Vliegenthart JFG, Shaw L, Reuter G, Schauer R (1992) Nature and biosynthesis of sialic acids in the starfish Asterias rubens. Identification of sialo-oligomers and detection of S-adenosyl-l-methionine: N-acylneuraminate 8-O-methyltransferase and CMP-N-acetylneuraminate monooxygenase activities. Biochimie 74:25–38PubMedCrossRefGoogle Scholar
  8. Bighignoli B, Niini T, Grahn RA, Pedersen NC, Millon LV, Polli M, Longeri M, Lyons LA (2007) Cytidine monophospho-N-acetylneuraminic acid hydroxylase (CMAH) mutations associated with the domestic cat AB blood group. BMC Genet 8:27PubMedCentralPubMedCrossRefGoogle Scholar
  9. Blanco R, Rengifo E, Cedeno M, Rengifo CE, Alonso DF, Carr A (2011) Immunoreactivity of the 14F7 Mab raised against N-Glycolyl GM3 Ganglioside in epithelial malignant tumors from digestive system. ISRN Gastroenterol 2011:645641PubMedCentralPubMedCrossRefGoogle Scholar
  10. Byres E, Paton AW, Paton JC, Lofling JC, Smith DF, Wilce MC, Talbot UM, Chong DC, Yu H, Huang S, Chen X, Varki NM, Varki A, Rossjohn J, Beddoe T (2008) Incorporation of a non-human glycan mediates human susceptibility to a bacterial toxin. Nature 456:648–652PubMedCentralPubMedCrossRefGoogle Scholar
  11. Chandrasekharan K, Yoon JH, Xu Y, deVries S, Camboni M, Janssen PM, Varki A, Martin PT (2010) A human-specific deletion in mouse Cmah increases disease severity in the mdx model of Duchenne muscular dystrophy. Sci Transl Med 2:42ra–54raCrossRefGoogle Scholar
  12. Chenu S, Gregoire A, Malykh Y, Visvikis A, Monaco L, Shaw L, Schauer R, Marc A, Goergen JL (2003) Reduction of CMP-N-acetylneuraminic acid hydroxylase activity in engineered Chinese hamster ovary cells using an antisense-RNA strategy. Biochim Biophys Acta 1622:133–144PubMedCrossRefGoogle Scholar
  13. Chou HH, Takematsu H, Diaz S, Iber J, Nickerson E, Wright KL, Muchmore EA, Nelson DL, Warren ST, Varki A (1998) A mutation in human CMP-sialic acid hydroxylase occurred after the Homo-Pan divergence. Proc Natl Acad Sci USA 95:11751–11756PubMedCrossRefGoogle Scholar
  14. Chou HH, Hayakawa T, Diaz S, Krings M, Indriati E, Leakey M, Paabo S, Satta Y, Takahata N, Varki A (2002) Inactivation of CMP-N-acetylneuraminic acid hydroxylase occurred prior to brain expansion during human evolution. Proc Natl Acad Sci USA 99:11736–11741PubMedCrossRefGoogle Scholar
  15. Commins SP, James HR, Kelly LA, Pochan SL, Workman LJ, Perzanowski MS, Kocan KM, Fahy JV, Nganga LW, Ronmark E, Cooper PJ, Platts-Mills TA (2011) The relevance of tick bites to the production of IgE antibodies to the mammalian oligosaccharide galactose-alpha-1,3-galactose. J Allergy Clin Immunol 127:1286–1293, e6PubMedCentralPubMedCrossRefGoogle Scholar
  16. Davies LR, Pearce OM, Tessier MB, Assar S, Smutova V, Pajunen M, Sumida M, Sato C, Kitajima K, Finne J, Gagneux P, Pshezhetsky A, Woods R, Varki A (2012) Metabolism of vertebrate amino sugars with N-Glycolyl Groups: resistance of α2-8-linked N-glycolylneuraminic acid to enzymatic cleavage. J Biol Chem 287:28917–28931PubMedCrossRefGoogle Scholar
  17. Diaz SL, Padler-Karavani V, Ghaderi D, Hurtado-Ziola N, Yu H, Chen X, Brinkman-Van der Linden EC, Varki A, Varki NM (2009) Sensitive and specific detection of the non-human sialic Acid N-glycolylneuraminic acid in human tissues and biotherapeutic products. PLoS One 4:e4241PubMedCentralPubMedCrossRefGoogle Scholar
  18. Fernandez-Marrero Y, Roque-Navarro L, Hernandez T, Dorvignit D, Molina-Perez M, Gonzalez A, Sosa K, Lopez-Requena A, Perez R, Mateo de Acosta C (2011) A cytotoxic humanized anti-ganglioside antibody produced in a murine cell line defective of N-glycolylated-glycoconjugates. Immunobiology 216:1239–1247PubMedCrossRefGoogle Scholar
  19. Ghaderi D, Taylor RE, Padler-Karavani V, Diaz S, Varki A (2010) Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins. Nat Biotechnol 28:863–867PubMedCentralPubMedCrossRefGoogle Scholar
  20. Ghaderi D, Springer SA, Ma F, Cohen M, Secrest P, Taylor RE, Varki A, Gagneux P (2011) Sexual selection by female immunity against paternal antigens can fix loss of function alleles. Proc Natl Acad Sci USA 108:17743–17748PubMedCrossRefGoogle Scholar
  21. Gollub M, Shaw L (2003) Isolation and characterization of cytidine-5′-monophosphate-N-acetylneuraminate hydroxylase from the starfish Asterias rubens. Comp Biochem Physiol B Biochem Mol Biol 134:89–101PubMedCrossRefGoogle Scholar
  22. Hayakawa T, Satta Y, Gagneux P, Varki A, Takahata N (2001) Alu-mediated inactivation of the human CMP-N-acetylneuraminic acid hydroxylase gene. Proc Natl Acad Sci USA 98:11399–11404PubMedCrossRefGoogle Scholar
  23. Hayakawa T, Aki I, Varki A, Satta Y, Takahata N (2006) Fixation of the human-specific CMP-N-acetylneuraminic acid hydroxylase pseudogene and implications of haplotype diversity for human evolution. Genetics 172:1139–1146PubMedCrossRefGoogle Scholar
  24. Hedlund M, Tangvoranuntakul P, Takematsu H, Long JM, Housley GD, Kozutsumi Y, Suzuki A, Wynshaw-Boris A, Ryan AF, Gallo RL, Varki N, Varki A (2007) N-glycolylneuraminic acid deficiency in mice: implications for human biology and evolution. Mol Cell Biol 27:4340–4346PubMedCentralPubMedCrossRefGoogle Scholar
  25. Hedlund M, Padler-Karavani V, Varki NM, Varki A (2008) Evidence for a human-specific mechanism for diet and antibody-mediated inflammation in carcinoma progression. Proc Natl Acad Sci USA 105:18936–18941PubMedCrossRefGoogle Scholar
  26. Hokke CH, Bergwerff AA, van Dedem GW, van Oostrum J, Kamerling JP, Vliegenthart JF (1990) Sialylated carbohydrate chains of recombinant human glycoproteins expressed in Chinese hamster ovary cells contain traces of N-glycolylneuraminic acid. FEBS Lett 275:9–14PubMedCrossRefGoogle Scholar
  27. Ikeda K, Yamamoto A, Nanjo A, Inuinaka C, Takama Y, Ueno T, Fukuzawa M, Nakano K, Matsunari H, Nagashima H, Miyagawa S (2012) A cloning of cytidine monophospho-N-acetylneuraminic acid hydroxylase from porcine endothelial cells. Transplant Proc 44:1136–1138PubMedCrossRefGoogle Scholar
  28. Irie A, Koyama S, Kozutsumi Y, Kawasaki T, Suzuki A (1998) The molecular basis for the absence of N-glycolylneuraminic acid in humans. J Biol Chem 273:15866–15871PubMedCrossRefGoogle Scholar
  29. Kavaler S, Morinaga H, Jih A, Fan W, Hedlund M, Varki A, Kim JJ (2011) Pancreatic {beta}-cell failure in obese mice with human-like CMP-Neu5Ac hydroxylase deficiency. FASEB J 25:1887–1893PubMedCrossRefGoogle Scholar
  30. Kawano T, Kozutsumi Y, Takematsu H, Kawasaki T, Suzuki A (1993) Regulation of biosynthesis of N-glycolylneuraminic acid-containing glycoconjugates: Characterization of factors required for NADH-dependent cytidine 5′monophosphate-N-acetylneuraminic acid hydroxylation. Glycoconj J 10:109–115PubMedCrossRefGoogle Scholar
  31. Kawano T, Kozutsumi Y, Kawasaki T, Suzuki A (1994) Biosynthesis of N-glycolylneuraminic acid-containing glycoconjugates. Purification and characterization of the key enzyme of the cytidine monophospho-N-acetylneuraminic acid hydroxylation system. J Biol Chem 269:9024–9029PubMedGoogle Scholar
  32. Kawano T, Koyama S, Takematsu H, Kozutsumi Y, Kawasaki H, Kawashima S, Kawasaki T, Suzuki A (1995) Molecular cloning of cytidine monophospho-N-acetylneuraminic acid hydroxylase. Regulation of species- and tissue-specific expression of N-glycolylneuraminic acid. J Biol Chem 270:16458–16463PubMedCrossRefGoogle Scholar
  33. Kelm S, Schauer R (1997) Sialic acids in molecular and cellular interactions. Int Rev Cytol 175:137–240PubMedCrossRefGoogle Scholar
  34. Kozutsumi Y, Kawano T, Yamakawa T, Suzuki A (1990) Participation of cytochrome b5 in CMP-N-acetylneuraminic acid hydroxylation in mouse liver cytosol. J Biochem 108:704–706 (Tokyo)PubMedGoogle Scholar
  35. Kozutsumi Y, Kawano T, Kawasaki H, Suzuki K, Yamakawa T, Suzuki A (1991) Reconstitution of CMP-N-acetylneuraminic acid hydroxylation activity using a mouse liver cytosol fraction and soluble cytochrome b5 purified from horse erythrocytes. J Biochem (Tokyo) 110:429–435Google Scholar
  36. Kuwaki K, Tseng YL, Dor FJ, Shimizu A, Houser SL, Sanderson TM, Lancos CJ, Prabharasuth DD, Cheng J, Moran K, Hisashi Y, Mueller N, Yamada K, Greenstein JL, Hawley RJ, Patience C, Awwad M, Fishman JA, Robson SC, Schuurman HJ, Sachs DH, Cooper DK (2005) Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience. Nat Med 11:29–31PubMedCrossRefGoogle Scholar
  37. Kyogashima M, Ginsburg V, Krivan HC (1989) Escherichia coli K99 binds to N-glycolylsialoparagloboside and N-glycolyl-GM3 found in piglet small intestine. Arch Biochem Biophys 270:391–397PubMedCrossRefGoogle Scholar
  38. Macauley MS, Chan J, Zandberg WF, He Y, Whitworth GE, Stubbs KA, Yuzwa SA, Bennet AJ, Varki A, Davies GJ, Vocadlo DJ (2012) Metabolism of vertebrate amino sugars with N-Glycolyl Groups: intracellular β-O-linked N-glycolylglucosamine (GlcNGc), UDP-GlcNGc, and the biochemical and structural rationale for the substrate tolerance of β-O-linked β-N-acetylglucosaminidase. J Biol Chem 287:28882–28897PubMedCrossRefGoogle Scholar
  39. Malykh YN, Shaw L, Schauer R (1998) The role of CMP-N-acetylneuraminic acid hydroxylase in determining the level of N-glycolylneuraminic acid in porcine tissues. Glycoconj J 15:885–893PubMedCrossRefGoogle Scholar
  40. Malykh YN, Schauer R, Shaw L (2001) N-Glycolylneuraminic acid in human tumours. Biochimie 83:623–634PubMedCrossRefGoogle Scholar
  41. Martensen I, Schauer R, Shaw L (2001) Cloning and expression of a membrane-bound CMP-N-acetylneuraminic acid hydroxylase from the starfish Asterias rubens. Eur J Biochem 268:5157–5166PubMedCrossRefGoogle Scholar
  42. Martin MJ, Muotri A, Gage F, Varki A (2005a) Human embryonic stem cells express an immunogenic nonhuman sialic acid. Nat Med 11:228–232PubMedCrossRefGoogle Scholar
  43. Martin MJ, Rayner JC, Gagneux P, Barnwell JW, Varki A (2005b) Evolution of human-chimpanzee differences in malaria susceptibility: relationship to human genetic loss of N-glycolylneuraminic acid. Proc Natl Acad Sci USA 102:12819–12824PubMedCrossRefGoogle Scholar
  44. Morito T, Nishimaki T, Masaki M, Yoshida H, Kasukawa R, Nakarai H, Kano K (1986) Studies on Hanganutziu-Deicher antigens-antibodies. I Hanganutziu-Deicher antibodies of IgG class in liver diseases. Int Arch Allergy Appl Immunol 81:204–208PubMedCrossRefGoogle Scholar
  45. Muchmore EA, Milewski M, Varki A, Diaz S (1989) Biosynthesis of N-glycolyneuraminic acid. The primary site of hydroxylation of N-acetylneuraminic acid is the cytosolic sugar nucleotide pool. J Biol Chem 264:20216–20223PubMedGoogle Scholar
  46. Mullins RJ, James H, Platts-Mills TA, Commins S (2012) Relationship between red meat allergy and sensitization to gelatin and galactose-alpha-1,3-galactose. J Allergy Clin Immunol 129:1334–1342, e1PubMedCentralPubMedCrossRefGoogle Scholar
  47. Naito Y, Takematsu H, Koyama S, Miyake S, Yamamoto H, Fujinawa R, Sugai M, Okuno Y, Tsujimoto G, Yamaji T, Hashimoto Y, Itohara S, Kawasaki T, Suzuki A, Kozutsumi Y (2007) Germinal center marker GL7 probes activation-dependent repression of N-glycolylneuraminic acid, a sialic acid species involved in the negative modulation of B-cell activation. Mol Cell Biol 27:3008–3022PubMedCentralPubMedCrossRefGoogle Scholar
  48. Nguyen DH, Tangvoranuntakul P, Varki A (2005) Effects of natural human antibodies against a nonhuman sialic acid that metabolically incorporates into activated and malignant immune cells. J Immunol 175:228–236PubMedGoogle Scholar
  49. Nishimaki T, Kano K, Milgrom F (1979) Hanganutziu-Deicher antigen and antibody in pathologic sera and tissues. J Immunol 122:2314–2318PubMedGoogle Scholar
  50. Padler-Karavani V, Varki A (2011) Potential impact of the non-human sialic acid N-glycolylneuraminic acid on transplant rejection risk. Xenotransplantation 18:1–5PubMedCentralPubMedCrossRefGoogle Scholar
  51. Padler-Karavani V, Yu H, Cao H, Chokhawala H, Karp F, Varki N, Chen X, Varki A (2008) Diversity in specificity, abundance, and composition of anti-Neu5Gc antibodies in normal humans: potential implications for disease. Glycobiology 18:818–830PubMedCrossRefGoogle Scholar
  52. Pan A, Sun Q, Bernstein AM, Schulze MB, Manson JE, Stampfer MJ, Willett WC, Hu FB (2012) Red meat consumption and mortality: results from 2 prospective cohort studies. Arch Intern Med 172:555–563PubMedCentralPubMedCrossRefGoogle Scholar
  53. Park JY, Park MR, Kwon DN, Kang MH, Oh M, Han JW, Cho SG, Park C, Kim DK, Song H, Oh JW, Kim JH (2011) Alpha 1,3-galactosyltransferase deficiency in pigs increases sialyltransferase activities that potentially raise non-gal xenoantigenicity. J Biomed Biotechnol 2011:560850PubMedCentralPubMedGoogle Scholar
  54. Pham T, Gregg CJ, Karp F, Chow R, Padler-Karavani V, Cao H, Chen X, Witztum JL, Varki NM, Varki A (2009) Evidence for a novel human-specific xeno-auto-antibody response against vascular endothelium. Blood 114:5225–5235PubMedCrossRefGoogle Scholar
  55. Raymond JB, Mahapatra S, Crick DC, Pavelka MSJ (2005) Identification of the namH gene, encoding the hydroxylase responsible for the N-glycolylation of the mycobacterial peptidoglycan. J Biol Chem 280:326–333PubMedCrossRefGoogle Scholar
  56. Schauer R (1970) Biosynthesis of N-glycoloylneuraminic acid by an ascorbic acid- or NADP-dependent N-acetyl hydroxylating “N-acetylneuraminate: O2-oxidoreductase” in homogenates of porcine submaxillary gland. Hoppe Seylers Z Physiol Chem 351:783–791PubMedCrossRefGoogle Scholar
  57. Schauer R, Schoop HJ, Faillard H (1968) On biosynthesis of the glycolyl groups of N-glycolylneuraminic acid oxidative conversion of N-acetyl groups to glycolyl groups. Hoppe Seylers Z Physiol Chem 349:645–652PubMedCrossRefGoogle Scholar
  58. Schauer R, Srinivasan GV, Coddeville B, Zanetta JP, Guerardel Y (2009) Low incidence of N-glycolylneuraminic acid in birds and reptiles and its absence in the platypus. Carbohydr Res 344:1494–1500PubMedCrossRefGoogle Scholar
  59. Schlenzka W, Shaw L, Schneckenburger P, Schauer R (1994) Purification and characterization of CMP-N-acetylneuraminic acid hydroxylase from pig submandibular glands. Glycobiology 4:675–684PubMedCrossRefGoogle Scholar
  60. Schlenzka W, Shaw L, Kelm S, Schmidt CL, Bill E, Trautwein AX, Lottspeich F, Schauer R (1996) CMP-N-acetylneuraminic acid hydroxylase: the first cytosolic Rieske iron-sulphur protein to be described in Eukarya. FEBS Lett 385:197–200PubMedCrossRefGoogle Scholar
  61. Schmidt CL, Shaw L (2001) A comprehensive phylogenetic analysis of Rieske and Rieske-type iron-sulphur proteins. J Bioenerg Biomembr 33:9–26PubMedCrossRefGoogle Scholar
  62. Schneckenburger P, Shaw L, Schauer R (1994) Purification, characterization and reconstitution of CMP-N-acetylneuraminate hydroxylase from mouse liver. Glycoconj J 11:194–203PubMedCrossRefGoogle Scholar
  63. Schoop HJ, Schauer R, Faillard H (1969) On the biosynthesis of N-glycolyneuraminic acid. Oxidative formation of N-glycolylneuraminic acid from N-acetylneuraminic acid. Hoppe Seylers Z Physiol Chem 350:155–162PubMedCrossRefGoogle Scholar
  64. Segatori VI, Otero LL, Fernandez LE, Gomez DE, Alonso DF, Gabri MR (2012) Antitumor protection by NGcGM3/VSSP vaccine against transfected B16 mouse melanoma cells overexpressing N-glycolylated gangliosides. In Vivo 26:609–617PubMedGoogle Scholar
  65. Shaw L, Schauer R (1988) The biosynthesis of N-glycoloylneuraminic acid occurs by hydroxylation of the CMP-glycoside of N-acetylneuraminic acid. Biol Chem Hoppe Seyler 369:477–486PubMedCrossRefGoogle Scholar
  66. Shaw L, Schneckenburger P, Carlsen J, Christiansen K, Schauer R (1992) Mouse liver cytidine-5′-monophosphate-N-acetylneuraminic acid hydroxylase–catalytic function and regulation. Eur J Biochem 206:269–277PubMedCrossRefGoogle Scholar
  67. Shaw L, Schneckenburger P, Schlenzka W, Carlsen J, Christiansen K, Jürgensen D, Schauer R (1994) CMP-N-acetylneuraminic acid hydroxylase from mouse liver and pig submandibular glands–interaction with membrane-bound and soluble cytochrome b5-dependent electron transport chains. Eur J Biochem 219:1001–1011PubMedCrossRefGoogle Scholar
  68. Tahara H, Ide K, Basnet NB, Tanaka Y, Matsuda H, Takematsu H, Kozutsumi Y, Ohdan H (2010) Immunological property of antibodies against N-Glycolylneuraminic acid epitopes in cytidine monophospho-N-acetylneuraminic acid hydroxylase-deficient mice. J Immunol 184:3269–3275PubMedCrossRefGoogle Scholar
  69. Takematsu H, Kawano T, Koyama S, Kozutsumi Y, Suzuki A, Kawasaki T (1994) Reaction mechanism underlying CMP-N-acetylneuraminic acid hydroxylation in mouse liver: formation of a ternary complex of cytochrome b5, CMP-N-acetylneuraminic acid, and a hydroxylation enzyme. J Biochem 115:381–386 (Tokyo)PubMedGoogle Scholar
  70. Tangvoranuntakul P, Gagneux P, Diaz S, Bardor M, Varki N, Varki A, Muchmore E (2003) Human uptake and incorporation of an immunogenic nonhuman dietary sialic acid. Proc Natl Acad Sci USA 100:12045–12050PubMedCrossRefGoogle Scholar
  71. Taylor RE, Gregg CJ, Padler-Karavani V, Ghaderi D, Yu H, Huang S, Sorensen RU, Chen X, Inostroza J, Nizet V, Varki A (2010) Novel mechanism for the generation of human xeno-autoantibodies against the nonhuman sialic acid N-glycolylneuraminic acid. J Exp Med 207:1637–1646PubMedCentralPubMedCrossRefGoogle Scholar
  72. Van Nunen SA, O’Connor KS, Clarke LR, Boyle RX, Fernando SL (2009) An association between tick bite reactions and red meat allergy in humans. Med J Aust 190:510–511PubMedGoogle Scholar
  73. Vancova M, Sterba J, Dupejova J, Simonova Z, Nebesarova J, Novotny MV, Grubhoffer L (2012) Uptake and incorporation of sialic acid by the tick Ixodes ricinus. J Insect Physiol 58:1277–1287PubMedCrossRefGoogle Scholar
  74. Varki A (2009) Multiple changes in sialic acid biology during human evolution. Glycoconj J 26:231–245PubMedCrossRefGoogle Scholar
  75. Varki A (2010) Colloquium paper: uniquely human evolution of sialic acid genetics and biology. Proc Natl Acad Sci USA 107(Suppl 2):8939–8946PubMedCrossRefGoogle Scholar
  76. Varki A, Gagneux P (2009) Human-specific evolution of sialic acid targets: explaining the malignant malaria mystery? Proc Natl Acad Sci USA 106:14739–14740PubMedCrossRefGoogle Scholar
  77. Varki A, Schauer R (2009) Sialic acids. In: Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, Hart GW, Etzler ME (eds) Essentials of glycobiology. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 199–218Google Scholar
  78. Varki NM, Strobert E, Dick EJ, Benirschke K, Varki A (2011) Biomedical differences between human and nonhuman Hominids: potential roles for uniquely human aspects of sialic acid biology. Annu Rev Pathol 6:365–393PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Department of Cellular and Molecular MedicineUniversity of California, San DiegoLa JollaUSA

Personalised recommendations