Human serum albumin

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human serum albumin
PDB rendering based on 1e7h.
Other data
LocusChr. 4 q13.3

Human serum albumin is the serum albumin found in human blood. It is the most abundant protein in human blood plasma; it constitutes about half of serum protein. It is produced in the liver. It is soluble in water and monomeric.

Albumin transports hormones, fatty acids, and other compounds, buffers pH, and maintains oncotic pressure, among other functions.

Albumin is synthesized in the liver as preproalbumin, which has an N-terminal peptide that is removed before the nascent protein is released from the rough endoplasmic reticulum. The product, proalbumin, is in turn cleaved in the Golgi vesicles to produce the secreted albumin.

The reference range for albumin concentrations in serum is approximately 35–50 g/L (3.5–5.0 g/dL).[1] It has a serum half-life of approximately 20 days. It has a molecular mass of 66.5 kDa.

The gene for albumin is located on chromosome 4 in locus 4q13.3 and mutations in this gene can result in anomalous proteins. The human albumin gene is 16,961 nucleotides long from the putative 'cap' site to the first poly(A) addition site. It is split into 15 exons that are symmetrically placed within the 3 domains thought to have arisen by triplication of a single primordial domain.


  • Maintains oncotic pressure
  • Transports thyroid hormones
  • Transports other hormones, in particular, ones that are fat-soluble
  • Transports fatty acids ("free" fatty acids) to the liver and to myocytes for utilization of energy
  • Transports unconjugated bilirubin
  • Transports many drugs; serum albumin levels can affect the half-life of drugs
  • Competitively binds calcium ions (Ca2+)
  • Serum albumin, as a negative acute-phase protein, is down-regulated in inflammatory states. As such, it is not a valid marker of nutritional status; rather, it is a marker of an inflammatory state
  • Prevents photodegradation of folic acid


Serum albumin is commonly measured by recording the change in absorbance upon binding to a dye such as bromocresol green or bromocresol purple.[2]

Reference ranges

Serum albumin concentration is typically 35–50 g/L (3.5–5.0 g/dL).[1]



Hypoalbuminemia means low blood albumin levels.[3] This can be caused by:


Hyperalbuminemia is an increased concentration of albumin in the blood.[5] Typically, this condition is due to dehydration.[5] Hyperalbuminemia has also been associated with high protein diets.[6]

Therapeutic uses

Human albumin solution or HSA is available for medical use, usually at concentrations of 5–25%.

Human albumin is often used to replace lost fluid and help restore blood volume in trauma, burns and surgery patients. A Cochrane systematic review[7] of 37 trials found no evidence that albumin, compared with cheaper alternatives such as saline, reduces the risk of dying.

Human serum albumin has been used as a component of a frailty index.[4]

It has not been shown to give better results than other fluids when used simply to replace volume, but is frequently used in conditions where loss of albumin is a major problem, such as liver disease with ascites.

Human serum albumin may be used to potentially reverse drug/chemical toxicity by binding to free drug/agent. (Tatlow, D, Poothencheri, S, Bhangal, R and Tatlow C. Novel method for rapid reversal of drug toxicity: A case report. doi|10.1111/1440-1681.12358). Ascentzi, P, Leboffe, L, Toti, D, Polticelli, F, and Trezza, V. Fipronil recognition by the FA1 site of human serum albumin. doi|10.1002/jmr.2713.


It has been known for a long time that human blood proteins like hemoglobin[8] and serum albumin[9][10] may undergo a slow non-enzymatic glycation, mainly by formation of a Schiff base between ε-amino groups of lysine (and sometimes arginine) residues and glucose molecules in blood (Maillard reaction). This reaction can be inhibited in the presence of antioxidant agents.[11] Although this reaction may happen normally,[9] elevated glycoalbumin is observed in diabetes mellitus.[10]

Glycation has the potential to alter the biological structure and function of the serum albumin protein.[12][13][14][15]

Moreover, the glycation can result in the formation of Advanced Glycation End-Products (AGE), which result in abnormal biological effects. Accumulation of AGEs leads to tissue damage via alteration of the structures and functions of tissue proteins, stimulation of cellular responses, through receptors specific for AGE-proteins, and generation of reactive oxygen intermediates. AGEs also react with DNA, thus causing mutations and DNA transposition. Thermal processing of proteins and carbohydrates brings major changes in allergenicity. AGEs are antigenic and represent many of the important neoantigens found in cooked or stored foods.[16] They also interfere with the normal product of nitric oxide in cells.[17]

Although there are several lysine and arginine residues in the serum albumin structure, very few of them can take part in the glycation reaction.[10][18] It is not clear exactly why only these residues are glycated in serum albumin, but it is suggested that non-covalent binding of glucose to serum albumin prior to the covalent bond formation might be the reason.[19]


The albumin is the predominant protein in most body fluids, its Cys34 represents the largest fraction of free thiols within body. The albumin Cys34 thiol exists in both reduced and oxidized forms.[20] In plasma of healthy young adults, 70–80% of total HSA contains the free sulfhydryl group of Cys34 in a reduced form or mercaptoalbumin (HSA-SH).[21] However, in pathological states characterized by oxidative stress and during the aging process, the oxidized form, or non-mercaptoalbumin (HNA), could predominate.[22] The albumin thiol reacts with radical hydroxyl (.OH), hydrogen peroxide (H2O2) and the reactive nitrogen species as peroxynitrite (ONOO.), and have been shown to oxidize Cys34 to sulfenic acid derivate (HSA-SOH), it can be recycled to mercapto-albumin; however at high concentrations of reactive species leads to the irreversible oxidation to sulfinic (HSA-SO2H) or sulfonic acid (HSA-SO3H) affecting its structure.[23] Presence of reactive oxygen species (ROS), can induce irreversible structural damage and alter protein activities.

Loss via kidneys

In the healthy kidney, albumin's size and negative electric charge exclude it from excretion in the glomerulus. This is not always the case, as in some diseases including diabetic nephropathy, which can sometimes be a complication of uncontrolled or of longer term diabetes in which proteins can cross the glomerulus. The lost albumin can be detected by a simple urine test.[24] Depending on the amount of albumin lost, a patient may have normal renal function, microalbuminuria, or albuminuria.

Amino acid sequence

The approximate sequence of human serum albumin is:[25]


Of the 609 amino acids in this sequence, encoded by the ALB gene and translated to form the precursor protein, only 585 amino acids are observed in the final product present in the blood; the first 24 amino acids (here italicized), including the signal peptide (1–18) and propeptide (19–22, or 19–24[citation needed]) portions, are cleaved after translation.


Human serum albumin has been shown to interact with FCGRT.[26]

See also


  1. 1.0 1.1 "Harmonisation of Reference Intervals" (PDF). Pathology Harmony. Retrieved 23 June 2013.
  2. "Albumin: analyte monograph" (PDF). Association for Clinical Biochemistry and Laboratory Medicine. Archived from the original (PDF) on 13 November 2012. Retrieved 23 June 2013.
  3. Anderson, Douglas M. (2000). Dorland's illustrated medical dictionary (29. ed.). Philadelphia [u.a.]: Saunders. p. 860. ISBN 0721682618.
  4. 4.0 4.1 Green P, Woglom AE, Genereux P, Daneault B, Paradis JM, Schnell S, Hawkey M, Maurer MS, Kirtane AJ, Kodali S, Moses JW, Leon MB, Smith CR, Williams M (2012). "The impact of frailty status on survival after transcatheter aortic valve replacement in older adults with severe aortic stenosis: a single-center experience". JACC Cardiovascular Interventions. 5 (9): 974–981. doi:10.1016/j.jcin.2012.06.011. PMC 3717525. PMID 22995885.
  5. 5.0 5.1 Walker, edited by H. Kenneth; Hall, W. Dallas; Schlossberg, J. Willis Hurst ; illustrations by Leon; Boyter, Charles H. (1990). Clinical methods : the history, physical, and laboratory examinations (3rd ed.). Boston: Butterworths. p. Chapter 101. ISBN 040990077X.
  6. Mutlu EA, Keshavarzian A, Mutlu GM (June 2006). "Hyperalbuminemia and elevated transaminases associated with high-protein diet". Scand. J. Gastroenterol. 41 (6): 759–60. doi:10.1080/00365520500442625. PMID 16716979.
  7. The Albumin Reviewers (Alderson P, Bunn F, Li Wan Po A, Li L, Pearson M, Roberts I, Schierhout G). Human albumin solution for resuscitation and volume expansion in critically ill patients" Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD001208. doi:10.1002/14651858.CD001208.pub2.
  8. Rahbar S (October 1968). "An abnormal hemoglobin in red cells of diabetics". Clin. Chim. Acta. 22 (2): 296–8. doi:10.1016/0009-8981(68)90372-0. PMID 5687098.
  9. 9.0 9.1 Day JF, Thorpe SR, Baynes JW (February 1979). "Nonenzymatically glucosylated albumin. In vitro preparation and isolation from normal human serum". J. Biol. Chem. 254 (3): 595–7. PMID 762083.
  10. 10.0 10.1 10.2 Iberg N, Flückiger R (October 1986). "Nonenzymatic glycosylation of albumin in vivo. Identification of multiple glycosylated sites". J. Biol. Chem. 261 (29): 13542–5. PMID 3759977.
  11. Jakus V, Hrnciarová M, Cársky J, Krahulec B, Rietbrock N (1999). "Inhibition of nonenzymatic protein glycation and lipid peroxidation by drugs with antioxidant activity". Life Sci. 65 (18–19): 1991–3. doi:10.1016/S0024-3205(99)00462-2. PMID 10576452.
  12. Mohamadi-Nejad A, Moosavi-Movahedi AA, Hakimelahi GH, Sheibani N (September 2002). "Thermodynamic analysis of human serum albumin interactions with glucose: insights into the diabetic range of glucose concentration". Int. J. Biochem. Cell Biol. 34 (9): 1115–24. doi:10.1016/S1357-2725(02)00031-6. PMID 12009306.
  13. Shaklai N, Garlick RL, Bunn HF (March 1984). "Nonenzymatic glycosylation of human serum albumin alters its conformation and function". J. Biol. Chem. 259 (6): 3812–7. PMID 6706980.
  14. Mendez DL, Jensen RA, McElroy LA, Pena JM, Esquerra RM (December 2005). "The effect of non-enzymatic glycation on the unfolding of human serum albumin". Arch. Biochem. Biophys. 444 (2): 92–9. doi:10.1016/ PMID 16309624.
  15. Mohamadi-Nejada A, Moosavi-Movahedi AA, Safariana S, Naderi-Maneshc MH, Ranjbarc B, Farzamid B, Mostafavie H, Larijanif MB, Hakimelahi GH, A (July 2002). "The thermal analysis of nonezymatic glycosylation of human serum albumin: differential scanning calorimetry and circular dichroism studies". Thermochimica Acta. 389 (1–2): 141–151. doi:10.1016/S0040-6031(02)00006-0.
  16. Kańska U, Boratyński J (2002). "Thermal glycation of proteins by D-glucose and D-fructose". Arch. Immunol. Ther. Exp. (Warsz.). 50 (1): 61–6. PMID 11916310.
  17. Rojas A, Romay S, González D, Herrera B, Delgado R, Otero K (February 2000). "Regulation of endothelial nitric oxide synthase expression by albumin-derived advanced glycosylation end products". Circ. Res. 86 (3): E50–4. doi:10.1161/01.RES.86.3.e50. PMID 10679490.
  18. Garlick RL, Mazer JS (May 1983). "The principal site of nonenzymatic glycosylation of human serum albumin in vivo". J. Biol. Chem. 258 (10): 6142–6. PMID 6853480.
  19. Marashi SA, Safarian S, Moosavi-Movahedi AA (2005). "Why major nonenzymatic glycation sites of human serum albumin are preferred to other residues?". Med. Hypotheses. 64 (4): 881. doi:10.1016/j.mehy.2004.11.007. PMID 15694713.
  20. Kawakami A, Kubota K, Yamada N, Tagami U, Takehana T, Sonaka I, Suzuki I, Hirayama K (2006). Identification and characterization of oxidized human serum albumin. FEBS J, 273:3346–3357. Doi: 10.1111/j.1742-4658.2006.05341.x
  21. Turell L, Carballal L, Botti H, Radi R, Alvarez B. (2009). Oxidation of the albumin thiol to sulfenic acid and its implications in the intravascular compartment. Braz J Med Biol Res 42:305–311.
  22. Rosas-Díaz M, Camarillo-Cadena M, Hernández-Arana A, Ramón-Gallegos E, Medina-Navarro R. (2015). Antioxidant capacity and structural changes of human serum albumin from patients in advanced stages of diabetic nephropathy and the effect of the dialysis. Molecular and Cellular Biochemistry, 404:193–201.
  23. Matsuyama Y, Terawaki H, Terada T, Era S. (2011). Albumin thiol oxidation and serum protein carbonyl formation are progressively enhanced with advancing stages of chronic kidney disease. Clin Exp Nephrol, 13(4):308–315.
  24. Microalbumin Urine Test
  25. Universal protein resource accession number P02768 for "Serum albumin" at UniProt.
  26. Chaudhury C, Mehnaz S, Robinson JM, Hayton WL, Pearl DK, Roopenian DC, Anderson CL (February 2003). "The Major Histocompatibility Complex–related Fc Receptor for IgG (FcRn) Binds Albumin and Prolongs Its Lifespan". J. Exp. Med. 197 (3): 315–22. doi:10.1084/jem.20021829. PMC 2193842. PMID 12566415.

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