Skip to main content
SpringerLink
Log in

Serum Sialic Acid as a Biomarker in Liver Disease

  • Reference work entry
  • First Online:
Biomarkers in Liver Disease

Abstract

Sialic acid (SA) is the nine-carbon N-acetylated derivatives of neuraminic acid. It is mostly found in the terminal position on nonreducing end of oligosaccharide chains of glycoproteins and glycolipids on the surface of cells and molecules. Due to this position and unique structural features, sialic acid is one of the most important molecules for life. The synthesis, catabolism, and attaching of this molecule to the oligosaccharide chains of proteins and lipids take place in the liver. Therefore, it has been hypothesized that the liver function can affect the concentration of protein-bound sialic acid (PBSA), lipid-bound sialic acid (LSA), and free sialic acid (FSA). The changes in liver status play an important role in the pathogenesis and progression of various liver diseases. In different liver diseases, the activity of enzymes involved in glycosylation is also changed. For the aberrant glycosylation of proteins and lipids in liver diseases, different glycosyltransferases are responsible. Therefore, the changes in the glycan structure of glycoproteins and glycolipids can be characteristic for the specific liver disease and could be potentially used in the diagnostics of liver pathology. The estimation of serum sialic acid level may be helpful as a biomarker of liver diseases. This study summarizes previously data about the changes in sialic acid concentrations in liver disease.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 449.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 549.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

A2M:

Alpha2-macroglobulin

AAT:

Alpha1-antitrypsin

AFP:

Alpha-fetoprotein

AFP-L3:

Fucosylated variant of alpha-fetoprotein

AGP:

Alpha1-acid glycoprotein

ALD:

Alcoholic liver disease

Apo-B:

Apolipoprotein B

Apo-J:

Apolipoprotein J

CDT:

Carbohydrate-deficient transferrin

CER:

Ceruloplasmin

CMP-Neu5Ac:

Cytidine monophosphate N-acetylneuraminic acid

CMP-NeuAc synthetase:

Cytidine monophosphate N-acetylneuraminic acid synthetase

CRP:

C-reactive protein

CTP:

Cytidine triphosphate

FSA:

Free sialic acid

GnT-III:

Glycosyltransferase III

GnT-V:

Glycosyltransferase V

HCC:

Hepatocellular carcinoma

HP:

Haptoglobin

IL-1:

Interleukin-1

IL-6:

Interleukin-6

LSA:

Lipid-bound sialic acid

ManNAc:

N-Acetyl d-mannosamine

ManNAc-6-kinase:

N-Acetylmannosamine 6-kinase

ManNAc-6-P:

N-Acetylmannosamine-6-phosphate

Neu5,9Ac:

N-Acetyl-9-O-acetylneuraminic acid

Neu5Ac:

N-Acetylneuraminic acid

Neu5Ac9-P:

N-Acetylneuraminic acid-9-phosphate

Neu5Ac-9-P-phosphatase:

N-Acetyl-d-neuraminyl-9-phosphatase

Neu5Ac-9-P-synthetase:

N-Acetyl-d-neuraminyl-9-phosphate synthetase

Neu5Glc:

N-Glycolylneuraminic acid

PBSA:

Protein-bound sialic acid

PEP:

Phosphoenolpyruvate

SA:

Sialic acid

TNF-α:

Tumor necrosis factor alpha

TNM:

Tumor-node-metastases classification

TRF:

Transferrin

TSA:

Total sialic acid

UDP-GlcNAc:

Uridine diphosphate N-acetylglucosamine

UDP-GlcNAc-2-epimerase:

Uridine diphosphate N-acetylglucosamine 2-epimerase

References

  • Arif S, Haq N, Hanif R, Khan AS, Rehman J, Mufti TA. Variations of serum sialic acid levels in liver cirrhosis. J Ayub Med Coll Abbottabad. 2005;17(3):54–7.

    Google Scholar 

  • Barkal A, Di Cesare JL. Influence of sialic acid groups on the retention of glycosphingolipids in blood plasma. Biochim Biophys Acta. 1975;398(2):287–93.

    Article  CAS  PubMed  Google Scholar 

  • Beatty P, Hanisch FG, Stolz DB, Finn OJ, Ciborowski P. Biochemical characterization of the soluble form of tumor antigen MUC1 isolated from sera and ascites fluid of breast and pancreatic cancer patients. Clin Cancer Res. 2001;7(3):781–7.

    Google Scholar 

  • Blomme B, Steenkiste C, Callewaert N, Vlierberghe H. Alteration of protein glycosylation in liver diseases. J Hepatol. 2009;50(3):592–603.

    Article  CAS  PubMed  Google Scholar 

  • Bork K, Horstkorte R, Weidemann W. Increasing the sialylation of therapeutic glycoproteins: the potential of the sialic acid biosynthetic pathway. J Pharm Sci. 2009;98(10):3499–508.

    Article  CAS  PubMed  Google Scholar 

  • Chrostek L, Cylwik B. Zaburzenia glikozylacji w chorobach wÄ…troby. Pol Merkuriusz Lek. 2011;31(181):60–4.

    CAS  Google Scholar 

  • Chrostek L, Cylwik B, Szmitkowski M, Korcz W. The diagnostic accuracy of carbohydrate- deficient transferrin, sialic acid and commonly used markers of alcohol abuse during abstinence. Clin Chim Acta. 2006;364(1-2):167–71.

    Article  CAS  PubMed  Google Scholar 

  • Chrostek L, Cylwik B, Panasiuk A, Brodowska-Adamusiak D, Gruszewska E. Lipid-bound sialic acid (LSA) in liver diseases of different etiologies. Ann Hepatol. 2011;10(2):150–4.

    CAS  PubMed  Google Scholar 

  • Chrostek L, Cylwik B, Gindzienska-Sieskiewicz E, Gruszewska E, Szmitkowski M, Sierakowski S. Sialic acid level reflects the disturbances of glycosylation and acute-phase reaction in rheumatic diseases. Rheumatol Int. 2014;34(3):393–9.

    Article  CAS  PubMed  Google Scholar 

  • Cylwik B, Chrostek L, Panasiuk A, Szmitkowski M. Serum total and free sialic acid in patients with chronic liver disease. Clin Chem Lab Med. 2010;48(1):137–9.

    Article  CAS  PubMed  Google Scholar 

  • Dabelic S, Flögel M, Maravić G, Lauc G. Stress causes tissue-specific changes in the sialyltransferase activity. Z Naturforsch C. 2004;59(3-4):276–80.

    Article  CAS  PubMed  Google Scholar 

  • Ghosh P, Hale EA, Lakshman MR. Plasma sialic acid index of apolipoprotein J (SIJ): a new alcohol intake marker. Alcohol. 2001;25(3):173–9.

    Article  CAS  PubMed  Google Scholar 

  • Gruszewska E, Chrostek L, Cylwik B, Tobolczyk J, Szmitowski M, KukliÅ„ski A, Kedra B. Serum sialic acid as a marker of pancreatic cancers. Clin Lab. 2013;59(7-8):781–8.

    CAS  PubMed  Google Scholar 

  • Gruszewska E, Cylwik B, Panasiuk A, Szmitkowski M, Flisiak R and Chrostek L. Total and free serum sialic acid concentration in liver diseases. BioMed Res Int. [online] 2014, article ID 876096. Available from: http://dx.doi.org/10.1155/2014/876096.

    Google Scholar 

  • Kloppel TM, Keenan TW, Freeman MJ, Morre DJ. Glycolipid-bound sialic acid in serum: increased levels in mice and humans bearing mammary carcinomas. Proc Natl Acad Sci U S A. 1977;74(7):3011–3.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kongtawelert P, Tangkijvanich P, Ong-Chai S, Poovorawan Y. Role of serum total sialic acid in differentiating cholangiocarcinoma from hepatocellular carcinoma. World J Gastroenterol. 2003;9(10):2178–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lakshman MR, Rao MN, Marmillot P. Alcohol and molecular regulation of protein glycosylation and function. Alcohol. 1999;19(3):239–47.

    Article  CAS  PubMed  Google Scholar 

  • Li Y, Chen X. Sialic acid metabolism and sialyltransferases: natural functions and applications. Appl Microbiol Biotechnol. 2012;94(4):887–905.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Malik K, Chugh K, Gupta G, Dahyia K, Gulia D, Tiwari R. Significance of protein bound sialic acid in alcoholic liver disease. IJIMS. 2015;2(6):8–12.

    CAS  Google Scholar 

  • Matsuzaki S, Itakura M, Iwamura K, Kamiguchi H. Serum sialic acid levels in liver cirrhosis and liver cancer. Gastroenterol Jpn. 1981;78(12):2395–401.

    CAS  Google Scholar 

  • Miyagi T, Wada T, Yamaguchi K, Shiozaki K, Sato I, Kakagawa Y, Yamanami H, Fujiya T. Human sialidase as a cancer marker. Proteomics. 2008;8(16):3303–11.

    Article  CAS  PubMed  Google Scholar 

  • Nakagawa T, Uozumi N, Nakano M, Mizuno-Horikawa Y, Okuyama N, Taguchi T, Gu J, Kondo A, Taniguchi N, Miyoshi E. Fucosylation of N-glycans regulates the secretion of hepatic glycoproteins into bile ducts. J Biol Chem. 2006;281(40):29797–806.

    Article  CAS  PubMed  Google Scholar 

  • Narayanan S. Sialic acid as a tumor marker. Ann Clin Lab Sci. 1994;24(4):376–84.

    CAS  PubMed  Google Scholar 

  • Nigam PK, Narain VS, Kumar A. Sialic acid in cardiovascular diseases. Indian J Clin Biochem. 2006;21(1):54–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Saitoh A, Aoyagi Y, Asakura H. Structural analysis on the sugar chains of human alpha1-antitrypsin: presence of fucosylated biantennary glycan in hepatocellular carcinoma. Arch Biochem Biophys. 1993;303(2):281–7.

    Article  CAS  PubMed  Google Scholar 

  • Schauer R, Kamerling JP. Chemistry biochemistry and biology of sialic acids. In: Montreuil J, Vliegenthart JFG, Schachter H, editors. Glycoproteins II. Amsterdam: Elsevier; 1997. p. 243–402.

    Chapter  Google Scholar 

  • Shim JK, Lee YC, Chung TH, Kim CH. Elevated expression of bisecting N-acetylglucosaminyltransferase-III gene in a human fetal hepatocyte cell line by hepatitis B virus. J Gastroenterol Hepatol. 2004;19(12):1374–87.

    Article  CAS  PubMed  Google Scholar 

  • Sillanaukee P, Pönniö M, Jääskeläinen IP. Occurrence of sialic acid in healthy humans and different disorders. Eur J Clin Invest. 1999;29(5):413–25.

    Article  CAS  PubMed  Google Scholar 

  • Stefenelli N, Klotz H, Engel A, Bauer P. Serum sialic acid in malignant tumors, bacterial infections, and chronic liver diseases. J Cancer Res Clin Oncol. 1985;109(1):55–9.

    Article  CAS  PubMed  Google Scholar 

  • Sterling RK, Jeffers L, Gordon F, Sherman M, Venook AP, Reddy KR, Satomura S, Schwartz ME. Clinical utility of AFP-L3% measurement in North American patients with HCV-related cirrhosis. Am J Gastroenterol. 2007;102(10):2196–205.

    Article  PubMed  Google Scholar 

  • Traving C, Schauer R. Structure, function and metabolism of sialic acids. Cell Mol Life Sci. 1998;54(12):1330–49.

    Article  CAS  PubMed  Google Scholar 

  • Tsutsumi M, Takase S. Usefulness of microheterogeneity of serum alpha 1-acidglycoprotein as a marker for alcohol abuse. Alcohol. 2001;25(3):181–4.

    Article  CAS  PubMed  Google Scholar 

  • Varki A. Sialic acids in human health and disease. Trends Mol Med. 2008;14(8):351–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Waters PJ, Lewry E, Peunock CA. Measurement of sialic acid in serum and urine: clinical applications and limitations. Ann Clin Biochem. 1992;29(6):625–37.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemical Diagnostics, Medical University of Bialystok, Waszyngtona 15A Street, 15-269, Bialystok, Poland

    Ewa Gruszewska & Lech Chrostek

Authors
  1. Ewa Gruszewska
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lech Chrostek
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ewa Gruszewska .

Editor information

Editors and Affiliations

  1. Department of Biomedical Science, Faculty of Science and Technology, University of Westminster, London, United Kingdom

    Vinood B. Patel

  2. Diabetes and Nutritional Sciences Research Division, Faculty of Life Science and Medicine, King’s College London, London, United Kingdom

    Victor R. Preedy

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer Science+Business Media Dordrecht

About this entry

Cite this entry

Gruszewska, E., Chrostek, L. (2017). Serum Sialic Acid as a Biomarker in Liver Disease. In: Patel, V., Preedy, V. (eds) Biomarkers in Liver Disease. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-7675-3_11

Download citation

Publish with us

Policies and ethics

Search

Navigation