Human serum albumin
Encyclopedia
Human serum albumin is the most abundant protein
in human
blood plasma
. It is produced in the liver
. Albumin constitutes about half of the blood serum protein. It is soluble and monomeric.
Albumin transports hormones, fatty acids, and other compounds, buffers pH, and maintains osmotic 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 blood is 3.4 to 5.4 g/dL. It has a serum half-life of approximately 20 days. It has a molecular mass
of 67 kDa.
The gene for albumin is located on chromosome 4 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.
on a Roche Modular or Olympus AU2700 analyser.
) can be caused by:
Human albumin is often used to replace lost fluid and help restore blood volume in trauma, burns and surgery patients. A Cochrane
systematic review
of 37 trials found no evidence that albumin, compared with cheaper alternatives such as saline, reduces the risk of dying.
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.
, 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 Glycosylation 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. 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.
, 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
, a major complication of uncontrolled 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
.
MKWVTFISLL FLFSSAYSRG VFRRDAHKSE VAHRFKDLGE ENFKALVLIA FAQYLQQCPF EDHVKLVNEV TEFAKTCVAD ESAENCDKSL HTLFGDKLCT VATLRETYGE MADCCAKQEP ERNECFLQHK DDNPNLPRLV RPEVDVMCTA FHDNEETFLK KYLYEIARRH PYFYAPELLF FAKRYKAAFT ECCQAADKAA CLLPKLDELR DEGKASSAKQ RLKCASLQKF GERAFKAWAV ARLSQRFPKA EFAEVSKLVT DLTKVHTECC HGDLLECADD RADLAKYICE NQDSISSKLK ECCEKPLLEK SHCIAEVEND EMPADLPSLA ADFVESKDVC KNYAEAKDVF LGMFLYEYAR RHPDYSVVLL LRLAKTYETT LEKCCAAADP HECYAKVFDE FKPLVEEPQN LIKQNCELFE QLGEYKFQNA LLVRYTKKVP QVSTPTLVEV SRNLGKVGSK CCKHPEAKRM PCAEDYLSVV LNQLCVLHEK TPVSDRVTKC CTESLVNRRP CFSALEVDET YVPKEFNAET FTFHADICTL SEKERQIKKQ TALVELVKHK PKATKEQLKA VMDDFAAFVE KCCKADDKET CFAEEGKKLV AASQAALGL
The italicized first 24 amino acids are signal and propeptide portions not observed in the transcribed, translated, and transported protein but present in the gene. There are 609 amino acids in this sequence with only 585 amino acids in the final product observed in the blood.
with FCGRT
.
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
in human
Human
Humans are the only living species in the Homo genus...
blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...
. It is produced in the liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
. Albumin constitutes about half of the blood serum protein. It is soluble and monomeric.
Albumin transports hormones, fatty acids, and other compounds, buffers pH, and maintains osmotic 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
Reference range
In health-related fields, a reference range or reference interval usually describes the variations of a measurement or value in healthy individuals...
for albumin concentrations in blood is 3.4 to 5.4 g/dL. It has a serum half-life of approximately 20 days. It has a molecular mass
Molecular mass
The molecular mass of a substance is the mass of one molecule of that substance, in unified atomic mass unit u...
of 67 kDa.
The gene for albumin is located on chromosome 4 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.
Function
- Maintains osmotic pressureOsmotic pressureOsmotic pressure is the pressure which needs to be applied to a solution to prevent the inward flow of water across a semipermeable membrane....
- Transports thyroid hormoneThyroid hormoneThe thyroid hormones, thyroxine and triiodothyronine , are tyrosine-based hormones produced by the thyroid gland primarily responsible for regulation of metabolism. An important component in the synthesis of thyroid hormones is iodine. The major form of thyroid hormone in the blood is thyroxine ,...
s - Transports other hormones, in particular, ones that are fat-soluble
- Transports fatty acids ("free" fatty acids) to the liver
- Transports unconjugated bilirubinBilirubinBilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...
- Transports many drugsMedicationA pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
; serum albumin levels can affect the half-life of drugs - Competitively binds calciumCalciumCalcium is the chemical element with the symbol Ca and atomic number 20. It has an atomic mass of 40.078 amu. Calcium is a soft gray alkaline earth metal, and is the fifth-most-abundant element by mass in the Earth's crust...
ions (Ca2+) - Buffers pHPHIn chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...
- 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 in inflammatory states
- Prevents photodegradation of folic acidFolic acidFolic acid and folate , as well as pteroyl-L-glutamic acid, pteroyl-L-glutamate, and pteroylmonoglutamic acid are forms of the water-soluble vitamin B9...
Measurement
Plasma albumin is a component of liver function tests (LFTs), but may be ordered separately. Albumin can be measured in serum (yellow-top tube), plain tube with no additives (red-top tube), or heparin plasma (green-top tube). The reference interval is 36 - 52 g/L. (upper limit increased from 47 g/L on the 15th June 2007). One of the methods used is bromocresol greenBromocresol green
Bromocresol Green is a dye of the triphenylmethane family , which is used as a pH indicator and as a tracking dye for DNA agarose gel electrophoresis. It can be used in its free acid form , or as a sodium salt...
on a Roche Modular or Olympus AU2700 analyser.
Reference ranges
Hypoalbuminemia
Low blood albumin levels (hypoalbuminemiaHypoalbuminemia
Hypoalbuminemia is a medical condition where levels of albumin in blood serum are abnormally low. It is a specific form of hypoproteinemia.Albumin is a major protein in the human body, making up about 60% of total human plasma protein by mass...
) can be caused by:
- Liver disease; cirrhosisCirrhosisCirrhosis is a consequence of chronic liver disease characterized by replacement of liver tissue by fibrosis, scar tissue and regenerative nodules , leading to loss of liver function...
of the liver is most common - Excess excretion by the kidneys (as in nephrotic syndromeNephrotic syndromeNephrotic syndrome is a nonspecific disorder in which the kidneys are damaged, causing them to leak large amounts of protein from the blood into the urine....
) - Excess loss in bowel (protein-losing enteropathy, e.g., Ménétrier's diseaseMénétrier's diseaseMénétrier disease , a disorder in which the gastric mucosal folds are enlarged , making the surface of the stomach look a bit like the brain gyri...
) - 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)
- Mutation causing analbuminemia (very rare)
Hyperalbuminemia
Typically, this condition is a sign of severe or chronic dehydration. Chronic dehydration needs to be treated with zinc as well as with water. Zinc reduces cell swelling caused by decreased intake of water (hypotonicity) and also increases retention of salt. In the dehydrated state, the body has too high an osmolarity and, it appears, discards zinc to prevent this. Zinc also regulates transport of the cellular osmolyte taurine, and albumin is known to increase cellular taurine absorption. Zinc has been shown to increase retinol (vitamin A) production from beta-carotene, and in lab experiments retinol reduced human albumin production. It is possible that a retinol (vitamin A) deficiency alone could cause albumin levels to become raised. Patients recovering from chronic dehydration may develop dry eyes as the body uses up its vitamin A store. It is interesting to note that retinol causes cells to swell with water (this is likely one reason that too much vitamin A is toxic). Hyperalbuminemia is also associated with high protein diets.Therapeutic Uses
Human albumin solution or HAS 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
Cochrane
Cochrane is a surname with multiple independent origins, two Scottish and one Irish. One Scottish version originates from a place in Scotland, and both the Irish surname and the other Scottish surname are anglicisations for a Gaelic language surname....
systematic review
Systematic review
A systematic review is a literature review focused on a research question that tries to identify, appraise, select and synthesize all high quality research evidence relevant to that question. Systematic reviews of high-quality randomized controlled trials are crucial to evidence-based medicine...
of 37 trials found no evidence that albumin, compared with cheaper alternatives such as saline, reduces the risk of dying.
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.
Glycosylation
It has been known for a long time that human blood proteins like hemoglobin and serum albumin may undergo a slow non-enzymatic glycationGlycation
Glycation is the result of the bonding of a protein or lipid molecule with a sugar molecule, such as fructose or glucose, without the controlling action of an enzyme. All blood sugars are reducing molecules. Glycation may occur either inside the body or outside the body...
, mainly by formation of a Schiff base between ε-amino groups of lysine (and sometimes arginine) residues and glucose molecules in blood (Maillard reaction
Maillard reaction
The Maillard reaction is a form of nonenzymatic browning similar to caramelization. It results from a chemical reaction between an amino acid and a reducing sugar, usually requiring heat....
). 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 Glycosylation 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. 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.
Loss via kidneys
In the healthy kidneyKidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
, albumin's size and negative electric charge exclude it from excretion in the glomerulus
Glomerulus
A glomerulus is a capillary tuft that is involved in the first step of filtering blood to form urine.A glomerulus is surrounded by Bowman's capsule, the beginning component of nephrons in the vertebrate kidney. A glomerulus receives its blood supply from an afferent arteriole of the renal...
. This is not always the case, as in some diseases including diabetic nephropathy
Diabetic nephropathy
Diabetic nephropathy , also known as Kimmelstiel-Wilson syndrome, or nodular diabetic glomerulosclerosis and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and diffuse...
, a major complication of uncontrolled 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
Microalbuminuria
Microalbuminuria occurs when the kidney leaks small amounts of albumin into the urine, in other words, when there is an abnormally high permeability for albumin in the renal glomerulus.-Diagnosis:...
, or albuminuria
Albuminuria
Albuminuria is a pathological condition wherein albumin is present in the urine. It is a type of proteinuria.Measurement=The amount of protein being lost in the urine can be quantified by collecting the urine for 24 hours, measuring a sample of the pooled urine, and extrapolating to the volume...
.
Amino acid sequence
The approximate sequence of human serum albumin is:MKWVTFISLL FLFSSAYSRG VFRRDAHKSE VAHRFKDLGE ENFKALVLIA FAQYLQQCPF EDHVKLVNEV TEFAKTCVAD ESAENCDKSL HTLFGDKLCT VATLRETYGE MADCCAKQEP ERNECFLQHK DDNPNLPRLV RPEVDVMCTA FHDNEETFLK KYLYEIARRH PYFYAPELLF FAKRYKAAFT ECCQAADKAA CLLPKLDELR DEGKASSAKQ RLKCASLQKF GERAFKAWAV ARLSQRFPKA EFAEVSKLVT DLTKVHTECC HGDLLECADD RADLAKYICE NQDSISSKLK ECCEKPLLEK SHCIAEVEND EMPADLPSLA ADFVESKDVC KNYAEAKDVF LGMFLYEYAR RHPDYSVVLL LRLAKTYETT LEKCCAAADP HECYAKVFDE FKPLVEEPQN LIKQNCELFE QLGEYKFQNA LLVRYTKKVP QVSTPTLVEV SRNLGKVGSK CCKHPEAKRM PCAEDYLSVV LNQLCVLHEK TPVSDRVTKC CTESLVNRRP CFSALEVDET YVPKEFNAET FTFHADICTL SEKERQIKKQ TALVELVKHK PKATKEQLKA VMDDFAAFVE KCCKADDKET CFAEEGKKLV AASQAALGL
The italicized first 24 amino acids are signal and propeptide portions not observed in the transcribed, translated, and transported protein but present in the gene. There are 609 amino acids in this sequence with only 585 amino acids in the final product observed in the blood.
Interactions
Human serum albumin has been shown to interactProtein-protein interaction
Protein–protein interactions occur when two or more proteins bind together, often to carry out their biological function. Many of the most important molecular processes in the cell such as DNA replication are carried out by large molecular machines that are built from a large number of protein...
with FCGRT
FCGRT
IgG receptor FcRn large subunit p51 is a protein that in humans is encoded by the FCGRT gene.-Interactions:FCGRT has been shown to interact with Human serum albumin.-Further reading:...
.
See also
- Reference ranges for common blood testsReference ranges for common blood testsReference ranges for blood tests are sets of values used by a health professional to interpret a set of medical test results from blood samples....
- Bovine serum albuminBovine serum albuminBovine serum albumin is a serum albumin protein derived from cows. It is often used as a protein concentration standard....
- Serum albuminSerum albuminSerum albumin, often referred to simply as albumin is a protein that in humans is encoded by the ALB gene.Serum albumin is the most abundant plasma protein in mammals. Albumin is essential for maintaining the osmotic pressure needed for proper distribution of body fluids between intravascular...
External links
- Human Albumin structure in the Protein data bankProtein Data BankThe Protein Data Bank is a repository for the 3-D structural data of large biological molecules, such as proteins and nucleic acids....
- Human Albumin information in the Swis-Prot/TrEMBL database
- Human Serum Albumin on the Human Protein Reference Database
- Albumin binding prediction
