Human serum albumin

Function

• 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. Competition between drugs for albumin binding sites may cause drug interaction by increasing the free fraction of one of the drugs, thereby affecting potency.
• 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
• Prevent pathogenic effects of Clostridioides difficile toxins

Measurement

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

Reference ranges

The normal range of human serum albumin in adults ( 3 y.o.) is 3.5–5.0 g/dL (35–50 g/L). For children less than three years of age, the normal range is broader, 2.9–5.5 g/dL.

Low albumin (hypoalbuminemia) may be caused by liver disease, nephrotic syndrome, burns, protein-losing enteropathy, malabsorption, malnutrition, late pregnancy, artefact, genetic variations and malignancy.

High albumin (hyperalbuminemia) is almost always caused by dehydration. In some cases of retinol (Vitamin A) deficiency, the albumin level can be elevated to high-normal values (e.g., 4.9 g/dL) because retinol causes cells to swell with water. (This is also the reason too much Vitamin A is toxic.) This swelling also likely occurs during treatment with 13-cis retinoic acid (isotretinoin), a pharmaceutical for treating severe acne, amongst other conditions. In lab experiments it has been shown that all-trans retinoic acid down regulates human albumin production.

Pathology

Hypoalbuminemia

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

• Liver disease; cirrhosis of the liver is most common
• Excess excretion by the kidneys (as in nephrotic syndrome)
• Excess loss in bowel (protein-losing enteropathy, e.g., Ménétrier's disease)
• Burns (plasma loss in the absence of skin barrier)
• Redistribution (hemodilution as in [pregnancy], increased vascular permeability or decreased lymphatic clearance)
• Acute disease states (referred to as a negative acute-phase protein)
• Malnutrition and wasting
• Mutation causing analbuminemia (very rare)
• Anorexia nervosa (most common cause in adolescents) In clinical medicine, hypoalbuminemia significantly correlates with a higher mortality rates in several conditions such as heart failure, post-surgery, COVID-19.

Hyperalbuminemia

Hyperalbuminemia is an increased concentration of albumin in the blood. Hyperalbuminemia has also been associated with high protein diets.

Medical use

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

Human albumin is often used to replace lost fluid and help restore blood volume in trauma, burns and surgery patients. There is no strong medical evidence that albumin administration (compared to saline) saves lives for people who have hypovolaemia or for those who are critically ill due to burns or hypoalbuminaemia. It is also not known if there are people who are critically ill that may benefit from albumin. Therefore, the Cochrane Collaboration recommends that it should not be used, except in clinical trials.

In acoustic droplet vaporization (ADV), albumin is sometimes used as a surfactant. ADV has been proposed as a cancer treatment by means of occlusion therapy.

Human serum albumin may be used to potentially reverse drug/chemical toxicity by binding to free drug/agent.

Human albumin may also be used in treatment of decompensated cirrhosis.

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

Glycation

It has been known for a long time that human blood proteins like hemoglobin and serum albumin 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. Although this reaction may happen normally, elevated glycoalbumin is observed in diabetes mellitus.

Glycation has the potential to alter the biological structure and function of the serum albumin protein.

Moreover, the glycation can result in the formation of advanced glycation end-products (AGEs), 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. They also interfere with the normal product of nitric oxide in cells.

Although there are several lysine and arginine residues in the serum albumin structure, very few of them can take part in the glycation reaction.

Oxidation

The albumin is the predominant protein in most body fluids, its Cys34 represents the largest fraction of free thiols within the body. The albumin Cys34 thiol exists in both reduced and oxidized forms. 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). However, in pathological states characterized by oxidative stress such as kidney disease, liver disease and diabetes the oxidized form, or non-mercaptoalbumin (HNA), could predominate. 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. 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. Depending on the amount of albumin lost, a patient may have normal renal function, microalbuminuria, or albuminuria.

Interactions

Human serum albumin has been shown to interact with FCGRT.

It might also interact with a yet-unidentified albondin (gp60), a certain pair of gp18/gp30, and some other proteins like osteonectin, hnRNPs, calreticulin, cubilin, and megalin.

References

References

1. "Harmonisation of Reference Intervals". Pathology Harmony.
2. (2019-11-10). "Hypoalbuminemia: Background, Pathophysiology, Etiology".
3. (September 2014). "Efficient loading and entrapment of tamoxifen in human serum albumin based nanoparticulate delivery system by a modified desolvation technique". Chemical Engineering Research and Design.
4. (September 2018). "Human Serum Albumin Is an Essential Component of the Host Defense Mechanism Against Clostridium difficile Intoxication". The Journal of Infectious Diseases.
5. "Albumin: analyte monograph". Association for Clinical Biochemistry and Laboratory Medicine.
6. "Normal Ranges for Common Laboratory Tests.".
7. (December 1984). "Protective effect of taurine, zinc and tocopherol on retinol-induced damage in human lymphoblastoid cells". The Journal of Nutrition.
8. (July 2006). "All-trans retinoic acid down-regulates human albumin gene expression through the induction of C/EBPbeta-LIP". The Biochemical Journal.
9. (2000). "Dorland's illustrated medical dictionary". Saunders.
10. (2022-04-20). "The Impact of Serum Albumin Levels on COVID-19 Mortality". Infectious Disease Reports.
11. (September 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.
12. (December 2010). "Serum albumin and mortality in acutely decompensated heart failure". American Heart Journal.
13. (August 2022). "Preoperative hypoalbuminemia in patients undergoing cardiac surgery: a meta-analysis". Surgery Today.
14. (April 2022). "The Impact of Serum Albumin Levels on COVID-19 Mortality". Infectious Disease Reports.
15. (1990). "Clinical methods: the history, physical, and laboratory examinations". Butterworths.
16. (June 2006). "Hyperalbuminemia and elevated transaminases associated with high-protein diet". Scandinavian Journal of Gastroenterology.
17. (November 2011). "Human albumin solution for resuscitation and volume expansion in critically ill patients". The Cochrane Database of Systematic Reviews.
18. (July 2021). "Expert consensus on the use of human serum albumin in critically ill patients". Chinese Medical Journal.
19. (May 2007). "Acoustic droplet vaporization threshold: effects of pulse duration and contrast agent". IEEE Transactions on Ultrasonics, Ferroelectrics, and Frequency Control.
20. (August 2018). "Fipronil recognition by the FA1 site of human serum albumin". Journal of Molecular Recognition.
21. (June 2018). "Long-term albumin administration in decompensated cirrhosis (ANSWER): an open-label randomised trial". Lancet.
22. (October 1968). "An abnormal hemoglobin in red cells of diabetics". Clinica Chimica Acta; International Journal of Clinical Chemistry.
23. (February 1979). "Nonenzymatically glucosylated albumin. In vitro preparation and isolation from normal human serum". The Journal of Biological Chemistry.
24. (October 1986). "Nonenzymatic glycosylation of albumin in vivo. Identification of multiple glycosylated sites". The Journal of Biological Chemistry.
25. (1999). "Inhibition of nonenzymatic protein glycation and lipid peroxidation by drugs with antioxidant activity". Life Sciences.
26. (September 2002). "Thermodynamic analysis of human serum albumin interactions with glucose: insights into the diabetic range of glucose concentration". The International Journal of Biochemistry & Cell Biology.
27. (March 1984). "Nonenzymatic glycosylation of human serum albumin alters its conformation and function". The Journal of Biological Chemistry.
28. (December 2005). "The effect of non-enzymatic glycation on the unfolding of human serum albumin". Archives of Biochemistry and Biophysics.
29. (July 2002). "The thermal analysis of nonezymatic glycosylation of human serum albumin: differential scanning calorimetry and circular dichroism studies". Thermochimica Acta.
30. (2002). "Thermal glycation of proteins by D-glucose and D-fructose". Archivum Immunologiae et Therapiae Experimentalis.
31. (February 2000). "Regulation of endothelial nitric oxide synthase expression by albumin-derived advanced glycosylation end products". Circulation Research.
32. (May 1983). "The principal site of nonenzymatic glycosylation of human serum albumin in vivo". The Journal of Biological Chemistry.
33. (July 2006). "Identification and characterization of oxidized human serum albumin. A slight structural change impairs its ligand-binding and antioxidant functions". The FEBS Journal.
34. (April 2009). "Oxidation of the albumin thiol to sulfenic acid and its implications in the intravascular compartment". Brazilian Journal of Medical and Biological Research = Revista Brasileira de Pesquisas Medicas e Biologicas.
35. (June 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.
36. (2017). "Clinical Implications Associated With the Posttranslational Modification-Induced Functional Impairment of Albumin in Oxidative". [[Journal of Pharmaceutical Sciences]].
37. (August 2009). "Albumin thiol oxidation and serum protein carbonyl formation are progressively enhanced with advancing stages of chronic kidney disease". Clinical and Experimental Nephrology.
38. "Microalbumin Urine Test". WebMD.
39. (February 2003). "The major histocompatibility complex-related Fc receptor for IgG (FcRn) binds albumin and prolongs its lifespan". The Journal of Experimental Medicine.
40. (2014). "Unraveling the mysteries of serum albumin-more than just a serum protein". Frontiers in Physiology.