A review of serum albumin
Jack Ho Wong
Affiliation
1School of Biomedical Sciences, Faculty of Medicine
2The Chinese University of Hong Kong, Hong Kong, China
Corresponding Author
Tzi Bun NG, The Chinese University of Hong Kong, Hong Kong, China; E-mail: b021770@mailserv.cuhk.edu.hk
Citation
Tzi Bun, N.G., et al. A Review of Serum Albumin (2018) J Cell Immunol Serum Biol 4(1): 1- 3.
Copy rights
© 2019 Tzi Bun, N.G. this is an Open access article distributed under the terms of Creative Commons Attribution 4.0 International License.
Abstract
Serum albumin is the most abundant protein in the blood circulation. It demonstrates a variety of activities including antioxidant activity, binding activity toward lipophilic hormones and xenobiotics, and hence protective effects against the endocrine disruptive activity of xenobiotics. Hypoalbminea is associated with poor disease prognosis. Glycated serum albumin can serve as a marker of glucose intolerance. Albumin is also associated with a variety of diseases including liver diseases, cancer, inflammatory diseases, renal disease and cardiovascular disease.
Introduction
Many proteins and peptides are present in the blood circulation. Serum albumin is unique in that it accounts for over 50% of the plasma proteins. It has been shown to be associated with a variety of diseases. This review is intended to cover the various aspects of serum albumin including structure, functions and association with diseases.
Structure and functions of albumin
Albumin is an anionic 66.5-kDa single-chain non glycoprotein composed of 585 amino acids and rich in aspartic acid and lysine. Albumin accounts for over 60% of the total plasma protein content it is heart- shaped in x-ray crystallography but is ellipsoid in solution. It is arranged in α-helices, with 17 disulfide bonds, and three homologous domains it possesses a free cysteine-derived thiol group at Cys-34, contributing to 80% of its redox activity. Each of the domains has an A subdomain consisting of 4α-helices and a B subdomain with 6 α-helices[1]. Albumin is synthesized in a precursor form called proalbumin, whose amino end has a basic hexapeptide attached to it. The binding of bilirubin and the primary binding of long-chain fatty acids are functions of separate domains[2]. Fish serum albumins exhibit structural diversity and play important roles in osmotic, plastic, and transport. Fish and mammalian albumin genes belong to one super family demonstrate analogous motifs[3]. Serum albumin displays binding activity toward metal ions and is involved in the transport and storage of amino acids, bilirubin, fatty acids, steroids and various other ligands. Intrinsic disorder is encoded in the amino acid sequence of serum albumin, and is related to functions of serum albumin[4]. Albumin binds lipophilic compounds, lipophilic hormones including steroid hormones, and phytochemicals and xenobiotics with binding ability to receptors for steroid hormones and other lipophilic hormones. Thus albumin prevents xenobiotic-induced endocrine disruption[5]. The binding affinity of dietary flavonoids to serum albumins due mainly to hydrophobic interaction is determined by bioavailability and structure-affinity relationship such as the position and degree of hydroxylation. Glycosylation lowers and substitution of methoxy group raises the affinity of flavonoids for serum albumins. Catechin gallates exhibit stronger serum albumin binding affinity compared with catechins and gallocatechins. Inorganic metal ions also affect the binding affinity[6].
Antioxidant activity: Albumin shows high binding affinity toward copper and low binding affinity toward iron, and scavenges free radicals such as hypochlorous acid and peroxynitrite and furnishes a thiol group. It reduces the availability of pro-oxidants and undergoes oxidation to prevent other macromolecules from being oxidized[7]. The specific antioxidant functions of human serum albumin are attributed to its multiple ligand-binding and free radical-trapping activities[8]. Sulfenic acid (RSOH) plays an important role in reversible and irreversible redox modulation by reactive species of proteins implicated in signal transduction pathways. Sulfenic acid in human serum albumin may participate in mixed disufide formation, lending credence to a role of human serum albumin -Cys34 in redox regulation in extracellular compartments[9].
Hypoalbuminemia: Hypoalbuminemia in adults is associated with poor postoperative prognosis in patients. However, intravenous albumin infusion does not alter the patient’s course of hospitalization[10].
Serum maternal serum ischemia-modified albumin concentrations: Determinations of maternal serum and fetal cord-blood ischemia-modified albumin concentrations serve as markers of oxidative stress status in preeclampsia patients[11].
Cancer: A decreased pretreatment serum albumin level implies a poor prognosis for renal cell carcinoma patients, and can be monitored for risk stratification and individualized treatment in renal cell carcinoma patients[12].
Diabetes mellitus: Increased glycated albumin levels are associated with development of insulin resistance in healthy subjects and secondary complications in diabetic patients. Hence glycated albumin levels may serve as a diagnostic marker for prediction of prediabetes and diabetic complications[13].
The plasma concentrations of glycated proteins increase in diabetes. The glycation of human serum albumin changes its structure and function. Such as causing a decline in the binding affinities for acidic drugs such as polyphenols and phenolic acids[14].
Cirrhosis: In cirrhotic patients undergoing paracentesis, albumin infusion prevents quick ascitic fluid reaccumulation and lowers the risk of post-paracentesis related circulatory dysfunction. Albumin is employed for hepatorenal syndrome and spontaneous bacterial peritonitis[15].
Renal disease: Post-translational modifications, like fragmentation of albumin, are found in nephrotic and diabetic patients. Proteolytic fragmentation of serum albumin is due to oxidative stress-induced enhanced protease susceptibility. Albumin fragmentation may exert a pathophysiological action in uremic syndrome[16].
Inflammation: The inflammatory prognostic index, calculated as C-reactive protein × (neutrophil / lymphocyte ratio)/serum albumin, may be a useful prognostic index for non-small cell lung cancer patients[17].
Cardiovascular disease: In spite of the association between higher serum albumin concentration and better outcome from epidemiologic evidence, albumin therapy in acute ischemic stroke did not lead to a better outcome[18].
Sepsis: Hypoalbuminemia common in the intensive care unit may be caused by declined hepatic albumin production and/or elevated losses or enhanced proteolytic degradation and clearance of albumin. Human serum albumin may benefit specific groups of hypoalbuminemic critically ill patients and improve organ function by reducing oxidative injury[1].
Conclusion
The foregoing account discloses the importance of serum albumin in health and disease. Albumin finds applications in medicine. As research continues, more functions will be unraveled and more applications will be found.
References
- 1. Tamion, F. Albumin in sepsis. (2010) Ann Fr Anesth Reanim 29(9): 629-634.
- 2. Peters, T. Serum albumin: recent progress in the understanding of its structure and biosynthesis. (1977) Clin Chem 23(1): 5-12.
Pubmed ||Crossref || Others
- 3. Andreeva, A.M. Structure of fish serum albumins. (2010) Zh Evol Biokhim Fiziol 46(2): 111-118.
- 4. Litus, E.A., Permyakov, S.E., Uversky, V.N., et al. Intrinsically Disordered Regions in Serum Albumin: What Are They For? (2017) Cell Biochem Biophys 76(1-2): 39-57.
- 5. Baker, M.E. Albumin, steroid hormones and the origin of vertebrates. (2002) J Endocrinol 175(1): 121-127.
- 6. Pal, S., Saha, C. A review on structure-affinity relationship of dietary flavonoids with serum albumins. (2014) J Biomol Struct Dyn 32(7): 1132-1147.
- 7. Sitar, M.E., Aydin, S., Cakatay, U. Human serum albumin and its relation with oxidative stress. (2013) Clin Lab 59(9-10): 945-952.
- 8. Taverna, M., Marie, A.L., Mira, J.P., et al. Specific antioxidant properties of human serum albumin. (2013) Ann Intensive Care 3(1): 4.
- 9. Carballal, S., Alvarez, B., Turell, L. Sulfenic acid in human serum albumin. (2007) Amino Acids 32(4): 543-551
- 10. Kim, S.M.c., Clave, S.A., Martindale, R.G. Hypoalbuminemia and Clinical Outcomes: What is the Mechanism behind theRelationship? (2017) Am Surg 83(11): 1220-1227.
- 11. Seshadri Reddy, V., Duggina, P. Maternal serum and fetal cord-blood ischemia-modified albumin concentrations in normal pregnancy and preeclampsia: a systematic review and meta-analysis. (2017) J Matern Fetal Neonatal Med 29: 1-12.
- 12. Chen, Z., Shao, Y., Wang, K., et al. Prognostic role of pretreatment serum albumin in renal cell carcinoma: a systematic review and meta-analysis. (2016) Onco Targets Ther 9: 6701-6710.
- 13. Neelofar, K., Ahmad, J. An overview of in vitro and in vivo glycation of albumin: a potential disease marker in diabetes mellitus. (2017) Glycoconj J 34(5): 575-584.
- 14. Cao, H., Chen, T., Shi, Y. Glycation of human serum albumin in diabetes: impacts on the structure and function. (2015) Curr Med Chem 22(1): 4-13.
- 15. Walayat, S., Martin, D., Patel, J. Role of albumin in cirrhosis: from a hospitalist’s perspective. (2017) J Community Hosp Intern Med Perspect 7(1): 8-14.
- 16. Donadio, C., Tognotti, D., Donadio, E. Albumin modification and fragmentation in renal disease. (2012) Clin Chim Acta 413(3-4): 391-395.
- 17. Dirican, N., Dirican, A., Anar, C., et al. New Inflammatory Prognostic Index, Based on C - reactive protein, the Neutrophil to Lymphocyte Ratio and Serum Albumin is Useful for Predicting Prognosis in Non-Small Cell Lung Cancer Cases. (2016) Asian Pac J Cancer Prev 17(12): 5101-5106.
- 18. Chien, S.C, Chen, C.Y., Lin, C.F., et al. Critical appraisal of the role of serum albumin in cardiovascular disease. (2017) Biomark Res 5: 31.
