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 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). 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 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 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
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
Serum albumin concentration is typically 35 - 50 g/L (3.5 - 5.0 g/dL)
Pathology
Hypoalbuminemia
Hypoalbuminemia is a 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)
Hyperalbuminemia
Hyperalbuminemia is an increased concentration of albumin in the blood. Typically, this condition is due to abrupt 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. Retinol causes cells to swell with water (this is most likely one reason that too much vitamin A is toxic). Hyperalbuminemia is also associated with high protein diets.
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 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.
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.
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 (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.
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-S3OH) 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.
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
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 (1â€"18) and propeptide (19â€"22, or 19â€"24) portions, are cleaved after translation.
Interactions
Human serum albumin has been shown to interact with FCGRT.
See also
- Bovine serum albumin
- Serum albumin
References
Further reading
External links
- Human Albumin structure in the Protein data bank
- Human Albumin information in the Swis-Prot/TrEMBL database
- Human Serum Albumin on the Human Protein Reference Database
- Albumin binding prediction
- Albumin at Lab Tests Online
- Albumin: analyte monograph from the Association for Clinical Biochemistry and Laboratory Medicine