Get Human Serum Albumin essential facts below. View Videos or join the Human Serum Albumin discussion. Add Human Serum Albumin to your PopFlock.com topic list for future reference or share this resource on social media.
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 21 days. It has a molecular mass 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 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.
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.
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 or for those who are critically ill due to burns or hypoalbuminaemia. It is also not known if there are people who are critically ill that may benefit from albumin.
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.
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 ?-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.
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, 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:
^di Masi A, Leboffe L, Polticelli F, Tonon F, Zennaro C, Caterino M, Stano P, Fischer S, Hägele M, Müller M, Kleger A, Papatheodorou P, Nocca G, Arcovito A, Gori A, Ruoppolo M, Barth H, Petrosillo N, Ascenzi P, Di Bella S (September 2018). "Human Serum Albumin Is an Essential Component of the Host Defense Mechanism Against Clostridium difficile Intoxication". The Journal of Infectious Diseases. 218 (9): 1424-1435. doi:10.1093/infdis/jiy338. PMID29868851.
^ abDay JF, Thorpe SR, Baynes JW (February 1979). "Nonenzymatically glucosylated albumin. In vitro preparation and isolation from normal human serum". The Journal of Biological Chemistry. 254 (3): 595-7. PMID762083.
^ abcIberg N, Flückiger R (October 1986). "Nonenzymatic glycosylation of albumin in vivo. Identification of multiple glycosylated sites". The Journal of Biological Chemistry. 261 (29): 13542-5. PMID3759977.
^Jakus V, Hrnciarová M, Cársky J, Krahulec B, Rietbrock N (1999). "Inhibition of nonenzymatic protein glycation and lipid peroxidation by drugs with antioxidant activity". Life Sciences. 65 (18-19): 1991-3. doi:10.1016/S0024-3205(99)00462-2. PMID10576452.
^Mohamadi-Nejad A, Moosavi-Movahedi AA, Hakimelahi GH, Sheibani N (September 2002). "Thermodynamic analysis of human serum albumin interactions with glucose: insights into the diabetic range of glucose concentration". The International Journal of Biochemistry & Cell Biology. 34 (9): 1115-24. doi:10.1016/S1357-2725(02)00031-6. PMID12009306.
^Shaklai N, Garlick RL, Bunn HF (March 1984). "Nonenzymatic glycosylation of human serum albumin alters its conformation and function". The Journal of Biological Chemistry. 259 (6): 3812-7. PMID6706980.
^Mendez DL, Jensen RA, McElroy LA, Pena JM, Esquerra RM (December 2005). "The effect of non-enzymatic glycation on the unfolding of human serum albumin". Archives of Biochemistry and Biophysics. 444 (2): 92-9. doi:10.1016/j.abb.2005.10.019. PMID16309624.
^Mohamadi-Nejada A, Moosavi-Movahedi AA, Safariana S, Naderi-Maneshc MH, Ranjbarc B, Farzamid B, Mostafavie H, Larijanif MB, Hakimelahi GH (July 2002). "The thermal analysis of nonezymatic glycosylation of human serum albumin: differential scanning calorimetry and circular dichroism studies". Thermochimica Acta. 389 (1-2): 141-151. doi:10.1016/S0040-6031(02)00006-0.
^Ka?ska U, Boraty?ski J (2002). "Thermal glycation of proteins by D-glucose and D-fructose". Archivum Immunologiae et Therapiae Experimentalis. 50 (1): 61-6. PMID11916310.
^Rojas A, Romay S, González D, Herrera B, Delgado R, Otero K (February 2000). "Regulation of endothelial nitric oxide synthase expression by albumin-derived advanced glycosylation end products". Circulation Research. 86 (3): E50-4. doi:10.1161/01.RES.86.3.e50. PMID10679490.
^Garlick RL, Mazer JS (May 1983). "The principal site of nonenzymatic glycosylation of human serum albumin in vivo". The Journal of Biological Chemistry. 258 (10): 6142-6. PMID6853480.
^Kawakami A, Kubota K, Yamada N, Tagami U, Takehana K, Sonaka I, Suzuki E, Hirayama K (July 2006). "Identification and characterization of oxidized human serum albumin. A slight structural change impairs its ligand-binding and antioxidant functions". The FEBS Journal. 273 (14): 3346-57. doi:10.1111/j.1742-4658.2006.05341.x. PMID16857017.
^Turell L, Carballal S, Botti H, Radi R, Alvarez B (April 2009). "Oxidation of the albumin thiol to sulfenic acid and its implications in the intravascular compartment". Brazilian Journal of Medical and Biological Research = Revista Brasileira de Pesquisas Medicas e Biologicas. 42 (4): 305-11. doi:10.1590/s0100-879x2009000400001. PMID19330257.
^Rosas-Díaz M, Camarillo-Cadena M, Hernández-Arana A, Ramón-Gallegos E, Medina-Navarro R (June 2015). "Antioxidant capacity and structural changes of human serum albumin from patients in advanced stages of diabetic nephropathy and the effect of the dialysis". Molecular and Cellular Biochemistry. 404 (1-2): 193-201. doi:10.1007/s11010-015-2378-2. PMID25758354.
^Matsuyama Y, Terawaki H, Terada T, Era S (August 2009). "Albumin thiol oxidation and serum protein carbonyl formation are progressively enhanced with advancing stages of chronic kidney disease". Clinical and Experimental Nephrology. 13 (4): 308-315. doi:10.1007/s10157-009-0161-y. PMID19363646.
Komatsu T, Nakagawa A, Curry S, Tsuchida E, Murata K, Nakamura N, Ohno H (September 2009). "The role of an amino acid triad at the entrance of the heme pocket in human serum albumin for O(2) and CO binding to iron protoporphyrin IX". Organic & Biomolecular Chemistry. 7 (18): 3836-41. doi:10.1039/b909794e. PMID19707690.
Silva AM, Hider RC (October 2009). "Influence of non-enzymatic post-translation modifications on the ability of human serum albumin to bind iron. Implications for non-transferrin-bound iron speciation". Biochimica et Biophysica Acta. 1794 (10): 1449-58. doi:10.1016/j.bbapap.2009.06.003. PMID19505594.
Otosu T, Nishimoto E, Yamashita S (February 2010). "Multiple conformational state of human serum albumin around single tryptophan residue at various pH revealed by time-resolved fluorescence spectroscopy". Journal of Biochemistry. 147 (2): 191-200. doi:10.1093/jb/mvp175. PMID19884191.
Juárez J, López SG, Cambón A, Taboada P, Mosquera V (July 2009). "Influence of electrostatic interactions on the fibrillation process of human serum albumin". The Journal of Physical Chemistry B. 113 (30): 10521-9. doi:10.1021/jp902224d. PMID19572666.
Fu BL, Guo ZJ, Tian JW, Liu ZQ, Cao W (August 2009). "[Advanced glycation end products induce expression of PAI-1 in cultured human proximal tubular epithelial cells through NADPH oxidase dependent pathway]". Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology. 25 (8): 674-7. PMID19664386.
Guo S, Shi X, Yang F, Chen L, Meehan EJ, Bian C, Huang M (September 2009). "Structural basis of transport of lysophospholipids by human serum albumin". The Biochemical Journal. 423 (1): 23-30. doi:10.1042/BJ20090913. PMID19601929.
de Jong PE, Gansevoort RT (2009). "Focus on microalbuminuria to improve cardiac and renal protection". Nephron Clinical Practice. 111 (3): c204-10, discussion c211. doi:10.1159/000201568. PMID19212124.
Page TA, Kraut ND, Page PM, Baker GA, Bright FV (September 2009). "Dynamics of loop 1 of domain I in human serum albumin when dissolved in ionic liquids". The Journal of Physical Chemistry B. 113 (38): 12825-30. doi:10.1021/jp904475v. PMID19711930.
Cui FL, Yan YH, Zhang QZ, Qu GR, Du J, Yao XJ (February 2010). "A study on the interaction between 5-Methyluridine and human serum albumin using fluorescence quenching method and molecular modeling". Journal of Molecular Modeling. 16 (2): 255-62. doi:10.1007/s00894-009-0548-4. PMID19588173.
Caridi G, Dagnino M, Simundic AM, Miler M, Stancic V, Campagnoli M, Galliano M, Minchiotti L (March 2010). "Albumin Benkovac (c.1175 A > G; p.Glu392Gly): a novel genetic variant of human serum albumin". Translational Research. 155 (3): 118-9. doi:10.1016/j.trsl.2009.10.001. PMID20171595.
Deeb O, Rosales-Hernández MC, Gómez-Castro C, Garduño-Juárez R, Correa-Basurto J (February 2010). "Exploration of human serum albumin binding sites by docking and molecular dynamics flexible ligand-protein interactions". Biopolymers. 93 (2): 161-70. doi:10.1002/bip.21314. PMID19785033.
Karahan SC, Koramaz I, Altun G, Uçar U, Topba? M, Mente?e A, Kopuz M (2010). "Ischemia-modified albumin reduction after coronary bypass surgery is associated with the cardioprotective efficacy of cold-blood cardioplegia enriched with N-acetylcysteine: a preliminary study". European Surgical Research. Europaische Chirurgische Forschung. Recherches Chirurgicales Europeennes. 44 (1): 30-6. doi:10.1159/000262324. PMID19955769.
Jin C, Lu L, Zhang RY, Zhang Q, Ding FH, Chen QJ, Shen WF (October 2009). "Association of serum glycated albumin, C-reactive protein and ICAM-1 levels with diffuse coronary artery disease in patients with type 2 diabetes mellitus". Clinica Chimica Acta; International Journal of Clinical Chemistry. 408 (1-2): 45-9. doi:10.1016/j.cca.2009.07.003. PMID19615354.