Serum albumin

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Serum albumin family
PDB 1o9x EBI.jpg
Structure of human serum albumin. [1]
Identifiers
SymbolSerum_albumin
Pfam PF00273
Pfam clan CL0282
InterPro IPR014760
SMART SM00103
PROSITE PS51438
SCOP2 1ao6 / SCOPe / SUPFAM
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
PDB 1ao6 , 1bj5 , 1bke , 1bm0 , 1e78 , 1e7a , 1e7b , 1e7c , 1e7e , 1e7f , 1e7g , 1e7h , 1e7i , 1gni , 1gnj , 1h9z , 1ha2 , 1hk1 , 1hk2 , 1hk3 , 1hk4 , 1hk5 , 1j78 , 1j7e , 1kw2 , 1kxp , 1lot , 1ma9 , 1n5u , 1o9x , 1tf0 , 1uor , 1ysx , 2bx8 , 2bxa , 2bxb , 2bxc , 2bxd , 2bxe , 2bxf , 2bxg , 2bxh , 2bxi , 2bxk , 2bxl , 2bxm , 2bxn , 2bxo , 2bxp , 2bxq , 2i2z , 2i30 , 2vdb , 2vue , 2vuf , 3b9l , 3b9m

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. [2] [3] [4] Other mammalian forms, such as bovine serum albumin, are chemically similar.

Contents

Serum albumin is produced by the liver, occurs dissolved in blood plasma and is the most abundant blood protein in mammals. Albumin is essential for maintaining the oncotic pressure needed for proper distribution of body fluids between blood vessels and body tissues; without albumin, the high pressure in the blood vessels would force more fluids out into the tissues. It also acts as a plasma carrier by non-specifically binding several hydrophobic steroid hormones and as a transport protein for hemin and fatty acids. Too much or too little circulating serum albumin may be harmful. Albumin in the urine usually denotes the presence of kidney disease. Occasionally albumin appears in the urine of normal persons following long periods of standing (postural albuminuria).

Function

Albumin functions primarily as a carrier protein for steroids, fatty acids, and thyroid hormones in the blood and plays a major role in stabilizing extracellular fluid volume by contributing to oncotic pressure (known also as colloid osmotic pressure) of plasma.

Because smaller animals (for example rats) function at a lower blood pressure, they need less oncotic pressure to balance this[ citation needed ], and thus need less albumin to maintain proper fluid distribution.

As an anionic protein, albumin binds readily to calcium in blood serum and contributes greatly to plasma calcium levels. As such, in clinical applications it is necessary to adjust serum total calcium concentration upward or downward if hypoalbuminemia or hyperalbuminemia is present, respectively (measured serum total calcium decreases by 0.8 mg/dL per unit decrease in albumin concentration below 4 g/dL). [5] [6]

Synthesis

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. [4]

Properties

Albumin is a globular, water-soluble, un-glycosylated serum protein of approximate molecular weight of 65,000 daltons.

Albumin (when ionized in water at pH 7.4, as found in the body) is negatively charged. The glomerular basement membrane is also negatively charged in the body; some studies suggest that this prevents the filtration of albumin in the urine. According to this theory, that charge plays a major role in the selective exclusion of albumin from the glomerular filtrate. A defect in this property results in nephrotic syndrome leading to albumin loss in the urine. Nephrotic syndrome patients are sometimes given albumin to replace the lost albumin.

Structure

The general structure of albumin is characterized by several long α helices allowing it to maintain a relatively static shape, which is essential for regulating blood pressure.

Serum albumin contains eleven distinct binding domains for hydrophobic compounds. One hemin and six long-chain fatty acids can bind to serum albumin at the same time. [7]

Types

Serum albumin is widely distributed in mammals.

See also

Related Research Articles

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 ; in healthy people, only trace amounts of it are present in urine, whereas larger amounts occur in the urine of patients with kidney disease. For a number of reasons, clinical terminology is changing to focus on albuminuria more than proteinuria.

<span class="mw-page-title-main">Oncotic pressure</span> Measure of pressure exerted by large dissolved molecules in biological fluids

Oncotic pressure, or colloid osmotic-pressure, is a type of osmotic pressure induced by the plasma proteins, notably albumin, in a blood vessel's plasma that causes a pull on fluid back into the capillary. Participating colloids displace water molecules, thus creating a relative water molecule deficit with water molecules moving back into the circulatory system within the lower venous pressure end of capillaries.

<span class="mw-page-title-main">Proteinuria</span> Presence of an excess of serum proteins in the urine

Proteinuria is the presence of excess proteins in the urine. In healthy persons, urine contains very little protein, less than 150 mg/day; an excess is suggestive of illness. Excess protein in the urine often causes the urine to become foamy. Severe proteinuria can cause nephrotic syndrome in which there is worsening swelling of the body.

<span class="mw-page-title-main">Nephrotic syndrome</span> Collection of symptoms due to kidney damage

Nephrotic syndrome is a collection of symptoms due to kidney damage. This includes protein in the urine, low blood albumin levels, high blood lipids, and significant swelling. Other symptoms may include weight gain, feeling tired, and foamy urine. Complications may include blood clots, infections, and high blood pressure.

<span class="mw-page-title-main">Serum protein electrophoresis</span> Laboratory test

Serum protein electrophoresis is a laboratory test that examines specific proteins in the blood called globulins. The most common indications for a serum protein electrophoresis test are to diagnose or monitor multiple myeloma, a monoclonal gammopathy of uncertain significance (MGUS), or further investigate a discrepancy between a low albumin and a relatively high total protein. Unexplained bone pain, anemia, proteinuria, chronic kidney disease, and hypercalcemia are also signs of multiple myeloma, and indications for SPE. Blood must first be collected, usually into an airtight vial or syringe. Electrophoresis is a laboratory technique in which the blood serum is applied to either an acetate membrane soaked in a liquid buffer, or to a buffered agarose gel matrix, or into liquid in a capillary tube, and exposed to an electric current to separate the serum protein components into five major fractions by size and electrical charge: serum albumin, alpha-1 globulins, alpha-2 globulins, beta 1 and 2 globulins, and gamma globulins.

<span class="mw-page-title-main">Calcium metabolism</span> Movement and regulation of calcium ions in and out of the body

Calcium metabolism is the movement and regulation of calcium ions (Ca2+) in (via the gut) and out (via the gut and kidneys) of the body, and between body compartments: the blood plasma, the extracellular and intracellular fluids, and bone. Bone acts as a calcium storage center for deposits and withdrawals as needed by the blood via continual bone remodeling.

The globulins are a family of globular proteins that have higher molecular weights than albumins and are insoluble in pure water but dissolve in dilute salt solutions. Some globulins are produced in the liver, while others are made by the immune system. Globulins, albumins, and fibrinogen are the major blood proteins. The normal concentration of globulins in human blood is about 2.6-3.5 g/dL.

alpha-2-Macroglobulin Large plasma protein found in the blood

α2-Macroglobulin (α2M) or alpha-2-macroglobulin is a large plasma protein found in the blood. It is mainly produced by the liver, and also locally synthesized by macrophages, fibroblasts, and adrenocortical cells. In humans it is encoded by the A2M gene.

<span class="mw-page-title-main">Glomerulus (kidney)</span> Functional unit of nephron

The glomerulus is a network of small blood vessels (capillaries) known as a tuft, located at the beginning of a nephron in the kidney. Each of the two kidneys contains about one million nephrons. The tuft is structurally supported by the mesangium, composed of intraglomerular mesangial cells. The blood is filtered across the capillary walls of this tuft through the glomerular filtration barrier, which yields its filtrate of water and soluble substances to a cup-like sac known as Bowman's capsule. The filtrate then enters the renal tubule of the nephron.

<span class="mw-page-title-main">Glomerulonephritis</span> Term for several kidney diseases

Glomerulonephritis (GN) is a term used to refer to several kidney diseases. Many of the diseases are characterised by inflammation either of the glomeruli or of the small blood vessels in the kidneys, hence the name, but not all diseases necessarily have an inflammatory component.

<span class="mw-page-title-main">Minimal change disease</span> Medical condition

Minimal change disease is a disease affecting the kidneys which causes nephrotic syndrome. Nephrotic syndrome leads to the loss of significant amounts of protein in the urine, which causes the widespread edema and impaired kidney function commonly experienced by those affected by the disease. It is most common in children and has a peak incidence at 2 to 6 years of age. MCD is responsible for 10–25% of nephrotic syndrome cases in adults. It is also the most common cause of nephrotic syndrome of unclear cause (idiopathic) in children.

<span class="mw-page-title-main">Nephritic syndrome</span> Medical condition

Nephritic syndrome is a syndrome comprising signs of nephritis, which is kidney disease involving inflammation. It often occurs in the glomerulus, where it is called glomerulonephritis. Glomerulonephritis is characterized by inflammation and thinning of the glomerular basement membrane and the occurrence of small pores in the podocytes of the glomerulus. These pores become large enough to permit both proteins and red blood cells to pass into the urine. By contrast, nephrotic syndrome is characterized by proteinuria and a constellation of other symptoms that specifically do not include hematuria. Nephritic syndrome, like nephrotic syndrome, may involve low level of albumin in the blood due to the protein albumin moving from the blood to the urine.

<span class="mw-page-title-main">Focal segmental glomerulosclerosis</span> Kidney disease

Focal segmental glomerulosclerosis (FSGS) is a histopathologic finding of scarring (sclerosis) of glomeruli and damage to renal podocytes. This process damages the filtration function of the kidney, resulting in protein presence in the urine due to protein loss. FSGS is a leading cause of excess protein loss—nephrotic syndrome—in children and adults. Signs and symptoms include proteinuria and edema. Kidney failure is a common long-term complication of the disease. FSGS can be classified as primary, secondary, or genetic, depending on whether a particular toxic or pathologic stressor or genetic predisposition can be identified as the cause. Diagnosis is established by renal biopsy, and treatment consists of glucocorticoids and other immune-modulatory drugs. Response to therapy is variable, with a significant portion of patients progressing to end-stage kidney failure. FSGS is estimated to occur in 7 persons per million, with males and African peoples at higher risk.

Hypoproteinemia is a condition where there is an abnormally low level of protein in the blood. There are several causes that all result in edema once serum protein levels fall below a certain threshold.

<span class="mw-page-title-main">Hypoalbuminemia</span> Medical condition

Hypoalbuminemia 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 abnormal distribution between body compartments. Patients often present with hypoalbuminemia as a result of another disease process such as malnutrition as a result of severe anorexia nervosa, sepsis, cirrhosis in the liver, nephrotic syndrome in the kidneys, or protein-losing enteropathy in the gastrointestinal tract. One of the roles of albumin is being the major driver of oncotic pressure in the bloodstream and the body. Thus, hypoalbuminemia leads to abnormal distributions of fluids within the body and its compartments. As a result, associated symptoms include edema in the lower legs, ascites in the abdomen, and effusions around internal organs. Laboratory tests aimed at assessing liver function diagnose hypoalbuminemia. Once identified, it is a poor prognostic indicator for patients with a variety of different diseases. Yet, it is only treated in very specific indications in patients with cirrhosis and nephrotic syndrome. Treatment instead focuses on the underlying cause of the hypoalbuminemia. Albumin is an acute negative phase respondent and not a reliable indicator of nutrition status.

<span class="mw-page-title-main">Bovine serum albumin</span> Serum albumin protein derived from cows

Bovine serum albumin is a serum albumin protein derived from cows. It is often used as a protein concentration standard in lab experiments.

<span class="mw-page-title-main">Human serum albumin</span> Albumin found in human blood

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.

<span class="mw-page-title-main">Albumin</span> Family of globular proteins

Albumin is a family of globular proteins, the most common of which are the serum albumins. All of the proteins of the albumin family are water-soluble, moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins are commonly found in blood plasma and differ from other blood proteins in that they are not glycosylated. Substances containing albumins are called albuminoids.

Congenital nephrotic syndrome is a rare kidney disease which manifests in infants during the first 3 months of life, and is characterized by high levels of protein in the urine (proteinuria), low levels of protein in the blood, and swelling. This disease is primarily caused by genetic mutations which result in damage to components of the glomerular filtration barrier and allow for leakage of plasma proteins into the urinary space.

α-Parinaric acid Chemical compound

α-Parinaric acid is a conjugated polyunsaturated fatty acid. Discovered by Tsujimoto and Koyanagi in 1933, it contains 18 carbon atoms and 4 conjugated double bonds. The repeating single bond-double bond structure of α-parinaric acid distinguishes it structurally and chemically from the usual "methylene-interrupted" arrangement of polyunsaturated fatty acids that have double-bonds and single bonds separated by a methylene unit (−CH2−). Because of the fluorescent properties conferred by the alternating double bonds, α-parinaric acid is commonly used as a molecular probe in the study of biomembranes.

References

  1. Sugio S, Kashima A, Mochizuki S, Noda M, Kobayashi K (June 1999). "Crystal structure of human serum albumin at 2.5 A resolution". Protein Engineering. 12 (6): 439–46. doi:10.1093/protein/12.6.439. PMID   10388840.
  2. Hawkins JW, Dugaiczyk A (1982). "The human serum albumin gene: structure of a unique locus". Gene. 19 (1): 55–8. doi:10.1016/0378-1119(82)90188-3. PMID   6292049.
  3. Harper ME, Dugaiczyk A (July 1983). "Linkage of the evolutionarily-related serum albumin and alpha-fetoprotein genes within q11-22 of human chromosome 4". American Journal of Human Genetics. 35 (4): 565–72. PMC   1685723 . PMID   6192711.
  4. 1 2 "Entrez Gene: albumin". U.S. National Library of Medicine.
  5. Goyal A, Anastasopoulou C, Ngu M, Singh S (8 May 2022). "Hypocalcemia". StatPearls. StatPearls Publishing LLC. PMID   28613662.
  6. Holliman K (March 2012). "Diagnosing a disorder with few symptoms". ACP Internist. American College of Physicians. Retrieved 13 June 2022.
  7. Zunszain PA, Ghuman J, Komatsu T, Tsuchida E, Curry S (July 2003). "Crystal structural analysis of human serum albumin complexed with hemin and fatty acid". BMC Structural Biology. 3: 6. doi: 10.1186/1472-6807-3-6 . PMC   166163 . PMID   12846933.