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Blood, Serum Albumins
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Serum albumin aka blood 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 chemically similar.

  • 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. The entire gene for human serum albumin (HSA) has been isolated from a genomic DNA library, carried in the lambda Charon 4A vector. Six independent isolates have been found to hybridize to a cloned HSA cDNA probe, and all six clones share restriction site sequence homology in the overlapping portion of their DNA. These results seem to indicate that the albumin gene is single-copy, or unique, within the human haploid genome. Measuring from the “CAP” site to the “poly(A)” addition site, albumin gene comprises 16.5 kb of DNA.
  • 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. Albumin and alpha-fetoprotein are structurally related serum proteins, having a similar gene structure and, conceivably, a common evolutionary origin. To test their relative arrangement in the human genome, the serum albumin and alpha-fetoprotein genes were mapped by in situ hybridization of cloned human albumin or alpha-fetoprotein cDNA to human mitotic chromosome preparations. Analysis of cells hybridized with the serum albumin probe showed that 39% of cells exhibited grains on the proximal portion of the long arm of chromosome 4 (bands q11-22), with these grains comprising 30% of all labeled sites throughout these mitoses. Similarly, in cells hybridized with the alpha-fetoprotein probe, 39% of cells were observed to contain silver grains on 4q11-22, these grains constituting 20% of all labeled sites in these cells. These results demonstrate chromosomal localization and linkage of the serum albumin and alpha-fetoprotein genes within bands q11-22 of the long arm of human chromosome 4.
  • “Entrez Gene: albumin”. U.S. National Library of Medicine. 

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).

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.

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

Main article: Albumin

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.

  • 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 Human serum albumin (HSA) is an abundant plasma protein that binds a wide variety of hydrophobic ligands including fatty acids, bilirubin, thyroxine and hemin. Although HSA-heme complexes do not bind oxygen reversibly, it may be possible to develop modified HSA proteins or heme groups that will confer this ability on the complex. We present here the crystal structure of a ternary HSA-hemin-myristate complex, formed at a 1:1:4 molar ratio, that contains a single hemin group bound to subdomain IB and myristate bound at six sites. The complex displays a conformation that is intermediate between defatted HSA and HSA-fatty acid complexes; this is likely to be due to low myristate occupancy in the fatty acid binding sites that drive the conformational change. The hemin group is bound within a narrow D-shaped hydrophobic cavity which usually accommodates fatty acid; the hemin propionate groups are coordinated by a triad of basic residues at the pocket entrance. The iron atom in the centre of the hemin is coordinated by Tyr161. The structure of the HSA-hemin-myristate complex (PDB ID 1o9x) reveals the key polar and hydrophobic interactions that determine the hemin-binding specificity of HSA. The details of the hemin-binding environment of HSA provide a structural foundation for efforts to modify the protein and/or the heme molecule in order to engineer complexes that have favourable oxygen-binding properties.

Types

Serum albumin is widely distributed in mammals.

  • The human version is human serum albumin.
  • Bovine serum albumin, or BSA, is commonly used in immunodiagnostic procedures, clinical chemistry reagents, cell culture media, protein chemistry research (including venom toxicity), and molecular biology laboratories (usually to leverage its non-specific protein binding properties).

See also

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. “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.

External links

Globular proteins

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