Human serum albumin is the
serum albumin
Serum albumin, often referred to simply as blood albumin, is an albumin (a type of globular protein) found in vertebrate blood. Human serum albumin is encoded by the ''ALB'' gene. Other mammalian forms, such as bovine serum albumin, are chemical ...
found in human
blood
Blood is a body fluid in the circulatory system of humans and other vertebrates that delivers necessary substances such as nutrients and oxygen to the cells, and transports metabolic waste products away from those same cells. Blood in the c ...
. It is the most abundant
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
in human
blood plasma
Blood plasma is a light amber-colored liquid component of blood in which blood cells are absent, but contains proteins and other constituents of whole blood in suspension. It makes up about 55% of the body's total blood volume. It is the intr ...
; it constitutes about half of
serum protein. It is produced in the
liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
. It is soluble in water, and it is
monomer
In chemistry, a monomer ( ; ''mono-'', "one" + '' -mer'', "part") is a molecule that can react together with other monomer molecules to form a larger polymer chain or three-dimensional network in a process called polymerization.
Classification
Mo ...
ic.
Albumin
Albumin is a family of globular proteins, the most common of which are the serum albumins. All the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins ...
transports hormones, fatty acids, and other compounds, buffers
pH, and maintains
oncotic pressure
Oncotic pressure, or colloid osmotic-pressure, is a form of osmotic pressure induced by the proteins, notably albumin, in a blood vessel's plasma (blood/liquid) that causes a pull on fluid back into the capillary. Participating colloids displace ...
, 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 apparatus
The Golgi apparatus (), also known as the Golgi complex, Golgi body, or simply the Golgi, is an organelle found in most eukaryotic cells. Part of the endomembrane system in the cytoplasm, it packages proteins into membrane-bound vesicles ins ...
to produce the secreted albumin.
The
reference range
In medicine and health-related fields, a reference range or reference interval is the range or the interval of values that is deemed normal for a physiological measurement in healthy persons (for example, the amount of creatinine in the blood, o ...
for albumin concentrations in serum is approximately 35–50 g/L (3.5–5.0 g/dL).
It has a serum half-life of approximately 21 days.
It has a
molecular mass
The molecular mass (''m'') is the mass of a given molecule: it is measured in daltons (Da or u). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The related quanti ...
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
Nucleotides are organic molecules consisting of a nucleoside and a phosphate. They serve as monomeric units of the nucleic acid polymers – deoxyribonucleic acid (DNA) and ribonucleic acid (RNA), both of which are essential biomolecules w ...
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.
Human serum albumin (HSA) is a highly water-soluble globular monomeric plasma protein with a relative molecular weight of 67 KDa, consisting of 585 amino acid residues, one sulfhydryl group and 17 disulfide bridges. Among nanoparticulate carriers, HSA nanoparticles have long been the center of attention in the pharmaceutical industry due to their ability to bind to various drug molecules, great stability during storage and in vivo usage, no toxicity and antigenicity,
biodegradability
Biodegradation is the breakdown of organic matter by microorganisms, such as bacteria and fungi. It is generally assumed to be a natural process, which differentiates it from composting. Composting is a human-driven process in which biodegradati ...
, reproducibility, scale up of the production process and a better control over release properties. In addition, significant amounts of drug can be incorporated into the particle matrix because of the large number of drug binding sites on the albumin molecule.
Function
* Maintains
oncotic pressure
Oncotic pressure, or colloid osmotic-pressure, is a form of osmotic pressure induced by the proteins, notably albumin, in a blood vessel's plasma (blood/liquid) that causes a pull on fluid back into the capillary. Participating colloids displace ...
* Transports
thyroid hormone
File:Thyroid_system.svg, upright=1.5, The thyroid system of the thyroid hormones T3 and T4
rect 376 268 820 433 Thyroid-stimulating hormone
rect 411 200 849 266 Thyrotropin-releasing hormone
rect 297 168 502 200 Hypothalamus
rect 66 216 386 25 ...
s
* Transports other hormones, in particular, ones that are fat-soluble
* Transports
fatty acids
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, f ...
("free" fatty acids) to the liver and to myocytes for utilization of energy
* Transports unconjugated
bilirubin
Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...
* Transports many
drugs
A drug is any chemical substance that causes a change in an organism's physiology or psychology when consumed. Drugs are typically distinguished from food and substances that provide nutritional support. Consumption of drugs can be via inhalat ...
; 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
Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...
ions (Ca
2+)
* 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
Folate, also known as vitamin B9 and folacin, is one of the B vitamins. Manufactured folic acid, which is converted into folate by the body, is used as a dietary supplement and in food fortification as it is more stable during processing and ...
* Prevent pathogenic effects of ''
Clostridioides difficile
''Clostridioides difficile'' ( syn. ''Clostridium difficile'') is a bacterium that is well known for causing serious diarrheal infections, and may also cause colon cancer. Also known as ''C. difficile'', or ''C. diff'' (), is Gram-positive spe ...
'' toxins
Measurement
Serum albumin is commonly measured by recording the change in
absorbance
Absorbance is defined as "the logarithm of the ratio of incident to transmitted radiant power through a sample (excluding the effects on cell walls)". Alternatively, for samples which scatter light, absorbance may be defined as "the negative lo ...
upon binding to a dye such as
bromocresol green
Bromocresol green (BCG) is a dye of the triphenylmethane family (triarylmethane dyes). It belongs to a class of dyes called sulfonephthaleins. It is used as a pH indicator in applications such as growth mediums for microorganisms and titrations. ...
or
bromocresol purple
Bromocresol purple (BCP) or 5′,5″-dibromo-''o''-cresolsulfophthalein, is a dye of the triphenylmethane family ( triarylmethane dyes) and a pH indicator. It is colored yellow below pH 5.2, and violet above pH 6.8. In its cyclic sulfonate ester ...
.
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
Hypoalbuminemia (or hypoalbuminaemia) is a medical sign in which the level of albumin in the blood is low. This can be due to decreased production in the liver, increased loss in the gastrointestinal tract or kidneys, increased use in the body, or ...
) may be caused by
liver disease
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Signs and symptoms
Some of the si ...
,
nephrotic syndrome, burns,
protein-losing enteropathy
Protein losing enteropathy refers to any condition of the gastrointestinal tract (e.g. damage to the gut wall) that results in a net loss of protein from the body.
Signs and symptoms
The signs/symptoms of protein losing enteropathy are consistent ...
,
malabsorption
Malabsorption is a state arising from abnormality in absorption of food nutrients across the gastrointestinal (GI) tract. Impairment can be of single or multiple nutrients depending on the abnormality. This may lead to malnutrition and a variety ...
,
malnutrition
Malnutrition occurs when an organism gets too few or too many nutrients, resulting in health problems. Specifically, it is "a deficiency, excess, or imbalance of energy, protein and other nutrients" which adversely affects the body's tissues a ...
, late pregnancy, artefact, genetic variations and malignancy.
High albumin (
hyperalbuminemia
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 it is monomeric.
Albumin ...
) is almost always caused by dehydration. In some cases of
retinol
Retinol, also called vitamin A1, is a fat-soluble vitamin in the vitamin A family found in food and used as a dietary supplement. As a supplement it is used to treat and prevent vitamin A deficiency, especially that which results in xeroph ...
(
Vitamin A
Vitamin A is a fat-soluble vitamin and an essential nutrient for humans. It is a group of organic compounds that includes retinol, retinal (also known as retinaldehyde), retinoic acid, and several provitamin A carotenoids (most notably bet ...
) 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 (
isotretnoin), 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
Hypoalbuminemia (or hypoalbuminaemia) is a medical sign in which the level of albumin in the blood is low. This can be due to decreased production in the liver, increased loss in the gastrointestinal tract or kidneys, increased use in the body, or ...
means low blood albumin levels. This can be caused by:
*
Liver disease
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Signs and symptoms
Some of the si ...
;
cirrhosis
Cirrhosis, also known as liver cirrhosis or hepatic cirrhosis, and end-stage liver disease, is the impaired liver function caused by the formation of scar tissue known as fibrosis due to damage caused by liver disease. Damage causes tissue repai ...
of the liver is most common
* Excess excretion by the
kidneys
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...
(as in
nephrotic syndrome)
* Excess loss in bowel (protein-losing enteropathy, e.g.,
Ménétrier's disease
Ménétrier disease is a rare, acquired, premalignant disease of the stomach characterized by massive gastric folds, excessive mucous production with resultant protein loss, and little or no acid production. The disorder is associated with excess ...
)
* Burns (plasma loss in the absence of skin barrier)
* Redistribution (hemodilution
s_in_pregnancy.html" ;"title="pregnancy.html" ;"title="s in pregnancy">s in pregnancy">pregnancy.html" ;"title="s in pregnancy">s 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
Anorexia nervosa, often referred to simply as anorexia, is an eating disorder characterized by low weight, food restriction, body image disturbance, fear of gaining weight, and an overpowering desire to be thin. ''Anorexia'' is a term of Gr ...
(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.
[ Typically, this condition is due to dehydration.] Hyperalbuminemia has also been associated with high protein diets.
Medical use
Human albumin solution (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. There is no strong medical evidence that albumin administration (compared to saline) saves lives for people who have hypovolaemia
Hypovolemia, also known as volume depletion or volume contraction, is a state of abnormally low extracellular fluid in the body. This may be due to either a loss of both salt and water or a decrease in blood volume. Hypovolemia refers to the los ...
or for those who are critically ill due to burns or hypoalbuminaemia
Hypoalbuminemia (or hypoalbuminaemia) is a medical sign in which the level of albumin in the blood is low. This can be due to decreased production in the liver, increased loss in the gastrointestinal tract or kidneys, increased use in the body, o ...
. It is also not known if there are people who are critically ill that may benefit from albumin. Therefore, the Cochrane Collaboration
Cochrane (previously known as the Cochrane Collaboration) is a British international charitable organisation formed to organise medical research findings to facilitate evidence-based choices about health interventions involving health profess ...
recommends that it should not be used, except in clinical trials.
In acoustic droplet vaporization Acoustic droplet vaporization (ADV) is the process by which superheated liquid droplets are phase-transitioned into gas bubbles by means of ultrasound. Perfluorocarbons and halocarbons are often used for the dispersed medium, which forms the co ...
(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
Glycation (sometimes called non-enzymatic glycosylation) is the covalent attachment of a sugar to a protein or lipid. Typical sugars that participate in glycation are glucose, fructose, and their derivatives. Glycation is the non-enzymatic proces ...
, mainly by formation of a Schiff base between ε-amino groups of lysine (and sometimes arginine) residues and glucose molecules in blood (Maillard reaction
The Maillard reaction ( ; ) is a chemical reaction between Amino acid, amino acids and Reducing sugar, reducing sugars that gives browned food its distinctive flavor. Searing, Seared steaks, fried dumplings, cookies and other kinds of biscuits, b ...
). 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 (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. 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 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 and during the aging process, 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
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
, albumin's size and negative electric charge exclude it from excretion in the glomerulus
''Glomerulus'' () is a common term used in anatomy to describe globular structures of entwined vessels, fibers, or neurons. ''Glomerulus'' is the diminutive of the Latin ''glomus'', meaning "ball of yarn".
''Glomerulus'' may refer to:
* the filter ...
. This is not always the case, as in some diseases including diabetic nephropathy
Diabetic nephropathy, also known as diabetic kidney disease, is the chronic loss of kidney function occurring in those with diabetes mellitus. Diabetic nephropathy is the leading causes of chronic kidney disease (CKD) and end-stage renal disease ...
, which can sometimes be a complication of uncontrolled or of longer term diabetes
Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ap ...
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
Microalbuminuria is a term to describe a moderate increase in the level of urine albumin. It occurs when the kidney leaks small amounts of albumin into the urine, in other words, when an abnormally high permeability for albumin in the glomerulus ...
, or albuminuria
Albuminuria is a pathological condition wherein the protein albumin is abnormally present in the urine. It is a type of proteinuria. Albumin is a major plasma protein (normally circulating in the blood); in healthy people, only trace amounts of ...
.
Interactions
Human serum albumin has been shown to interact
Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization using innovative strategies to advocate for the legal and human rights of children with intersex traits. The organizati ...
with FCGRT
The neonatal Fc receptor (also FcRn, IgG receptor FcRn large subunit p51, or Francis Brambell, Brambell receptor) is a protein that in humans is encoded by the ''FCGRT'' gene. It is an Fc receptor, IgG Fc receptor which is similar in structure to ...
.
It might also interact with a yet-unidentified albondin (gp60), a certain pair of gp18/gp30, and some other proteins like osteonectin
Osteonectin (ON) also known as secreted protein acidic and rich in cysteine (SPARC) or basement-membrane protein 40 (BM-40) is a protein that in humans is encoded by the ''SPARC'' gene.
Osteonectin is a glycoprotein in the bone that binds calciu ...
, hnRNPs Heterogeneous nuclear ribonucleoproteins (hnRNPs) are complexes of RNA and protein present in the cell nucleus during gene transcription and subsequent post-transcriptional modification of the newly synthesized RNA (pre-mRNA). The presence of the p ...
, calreticulin
Calreticulin also known as calregulin, CRP55, CaBP3, calsequestrin-like protein, and endoplasmic reticulum resident protein 60 (ERp60) is a protein that in humans is encoded by the ''CALR'' gene.
Calreticulin is a multifunctional soluble prote ...
, cubilin
Cubilin is a protein that in humans is encoded by the ''CUBN'' gene.
Function
Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubilin shows a re ...
, and megalin
Low density lipoprotein receptor-related protein 2 also known as LRP-2 or megalin is a protein which in humans is encoded by the ''LRP2'' gene.
Function
LRP2 was identified as the antigen of rat experimental membranous nephropathy (Heyman neph ...
.
See also
* Bovine serum albumin
Bovine serum albumin (BSA or "Fraction V") is a serum albumin protein derived from cows. It is often used as a protein concentration standard in lab experiments.
The nickname "Fraction V" refers to albumin being the fifth fraction of the origin ...
* Serum albumin
Serum albumin, often referred to simply as blood albumin, is an albumin (a type of globular protein) found in vertebrate blood. Human serum albumin is encoded by the ''ALB'' gene. Other mammalian forms, such as bovine serum albumin, are chemical ...
References
Further reading
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External links
Human Albumin structure
in the Protein data bank
The Protein Data Bank (PDB) is a database for the three-dimensional structural data of large biological molecules, such as proteins and nucleic acids. The data, typically obtained by X-ray crystallography, NMR spectroscopy, or, increasingly, cry ...
Human Serum Albumin
on th
Human Protein Reference Database
Albumin binding prediction
* Albumin a
Lab Tests Online
Albumin: analyte monograph
from the Association for Clinical Biochemistry and Laboratory Medicine
*
{{DEFAULTSORT:Human Serum Albumin
Blood proteins
Liver function tests