Human serum albumin: Difference between revisions

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{{PBB_Controls
{{infobox protein
| update_page = yes
| Name = [[Serum albumin|human serum albumin]]
| require_manual_inspection = no
| caption = [[Protein Data Bank|PDB]] rendering based on 1e7h.
| update_protein_box = yes
| image = 1e7h.jpg
| update_summary = no
| width = 270
| update_citations = yes
| HGNCid = 399
| Symbol = [[Serum albumin|ALB]]
| AltSymbols =
| EntrezGene = 213
| OMIM = 103600
| RefSeq = NM_000477
| UniProt = P02768
| PDB = 1E7H
| ECnumber =
| Chromosome = 4
| Arm = q
| Band = 13.3
| LocusSupplementaryData =
}}
}}
{{GNF_Protein_box
'''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 (blood)|serum]] protein. It is produced in the [[liver]]. It is soluble in water and [[monomer]]ic.
| image = ALB_structure.png
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1e7h.
| Name = Albumin
| HGNCid = 399
| Symbol = ALB
| AltSymbols =; DKFZp779N1935; PRO0883; PRO0903; PRO1341
| OMIM = 103600
| ECnumber = 
| Homologene = 405
| MGIid = 87991
| GeneAtlas_image1 = PBB_GE_ALB_211298_s_at_tn.png
| Function = {{GNF_GO|id=GO:0003677 |text = DNA binding}} {{GNF_GO|id=GO:0005386 |text = transmembrane transporter activity}} {{GNF_GO|id=GO:0005504 |text = fatty acid binding}} {{GNF_GO|id=GO:0005507 |text = copper ion binding}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008144 |text = drug binding}} {{GNF_GO|id=GO:0015643 |text = toxin binding}} {{GNF_GO|id=GO:0016209 |text = antioxidant activity}} {{GNF_GO|id=GO:0019825 |text = oxygen binding}} {{GNF_GO|id=GO:0030170 |text = pyridoxal phosphate binding}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}}
| Component = {{GNF_GO|id=GO:0005576 |text = extracellular region}} {{GNF_GO|id=GO:0005615 |text = extracellular space}} {{GNF_GO|id=GO:0043234 |text = protein complex}}
| Process = {{GNF_GO|id=GO:0006810 |text = transport}} {{GNF_GO|id=GO:0009267 |text = cellular response to starvation}} {{GNF_GO|id=GO:0019836 |text = hemolysis by symbiont of host red blood cells}} {{GNF_GO|id=GO:0043066 |text = negative regulation of apoptosis}} {{GNF_GO|id=GO:0043072 |text = negative regulation of non-apoptotic programmed cell death}} {{GNF_GO|id=GO:0051659 |text = maintenance of mitochondrion localization}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 213
    | Hs_Ensembl = ENSG00000163631
    | Hs_RefseqProtein = NP_000468
    | Hs_RefseqmRNA = NM_000477
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 4
    | Hs_GenLoc_start = 74488870
    | Hs_GenLoc_end = 74505996
    | Hs_Uniprot = P02768
    | Mm_EntrezGene = 11657
    | Mm_Ensembl = ENSMUSG00000029368
    | Mm_RefseqmRNA = NM_009654
    | Mm_RefseqProtein = NP_033784
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 5
    | Mm_GenLoc_start = 91536101
    | Mm_GenLoc_end = 91551800
    | Mm_Uniprot = Q3TV03
  }}
}}
{{CMG}}


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&nbsp;g/L (3.5–5.0&nbsp;g/dL).<ref name="Pathology Harmony">{{cite web|title=Harmonisation of Reference Intervals|url=http://www.acb.org.uk/docs/Pathology%20Harmony%20for%20web.pdf|work=pathologyharmony.co.uk|publisher=Pathology Harmony|accessdate=23 June 2013}}</ref>  It has a serum half-life of approximately 20 days. It has a [[molecular mass]] of 66.5&nbsp;kDa.


'''Human serum albumin''' is the most abundant [[protein]] in [[human]] [[blood plasma]]. It is produced in the [[liver]].  Albumin comprises about half of the blood serum protein.  It is soluble and monomeric.
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.


The gene for albumin is located on chromosome 4 and mutations in this gene can result in various 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 which are symmetrically placed within the 3 domains that are thought to have arisen by triplication of a single primordial domain.   
==Function==
 
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 30 to 50 g/L. It has a serum half-life of approximately 20 days.  It has a [[molecular mass]] of 67 kDa.
 
==Functions of albumin==
* Maintains [[oncotic pressure]]
* Maintains [[oncotic pressure]]
* Transports [[thyroid]] [[hormone]]s
* Transports [[thyroid hormone]]s
* Transports other hormones, particularly fat soluble ones
* Transports other hormones, in particular, ones that are fat-soluble
* Transports [[fatty acids]] ("free" fatty acids) to the liver
* Transports [[fatty acids]] ("free" fatty acids) to the liver and to myocytes for utilization of energy
* Transports unconjugated [[bilirubin]]
* Transports unconjugated [[bilirubin]]
* Transports many [[medication|drugs]], and serum albumin levels can affect the half-life of drugs.
* Transports many [[medication|drugs]]; serum albumin levels can affect the half-life of drugs
* Competitively binds [[calcium]] ions (Ca<sup>2+</sup>)
* Competitively binds [[calcium]] ions (Ca<sup>2+</sup>)
* Buffers [[pH]]
* 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]].<ref>{{cite web|title=Albumin: analyte monograph |url=http://www.acb.org.uk/docs/NHLM/Albumin.pdf |publisher=Association for Clinical Biochemistry and Laboratory Medicine |accessdate=23 June 2013 |deadurl=yes |archiveurl=https://web.archive.org/web/20121113144057/http://www.acb.org.uk/docs/NHLM/Albumin.pdf |archivedate=13 November 2012 |df= }}</ref>
 
==Reference ranges==
Serum albumin concentration is typically 35–50&nbsp;g/L (3.5–5.0&nbsp;g/dL).<ref name="Pathology Harmony"/>


==Pathology==
==Pathology==
===Hypoalbuminemia===
===Hypoalbuminemia===
Low blood albumin levels ([[hypoalbuminemia]]) can be caused by:
[[Hypoalbuminemia]] means low blood albumin levels.<ref>{{cite book|last1=Anderson|first1=Douglas M.|title=Dorland's illustrated medical dictionary|date=2000|publisher=Saunders|location=Philadelphia [u.a.]|isbn=0721682618|page=860|edition=29.}}</ref> This can be caused by:


* liver disease / [[Cirrhosis]] of the liver (most commonly)
* [[Liver disease]]; [[cirrhosis]] of the liver is most common
* Decreased production (as in starvation/malnutrition/malabsorption)
* Excess excretion by the [[kidneys]] (as in [[nephrotic syndrome]])
* Excess excretion by the [[kidneys]] (as in [[nephrotic syndrome]])
* Excess loss in bowel (protein losing enteropathy e.g. [[Menetrier's disease]])
* Excess loss in bowel (protein-losing enteropathy, e.g., [[Ménétrier's disease]])
* Burns (Plasma loss in the absence of skin barrier)
* Burns (plasma loss in the absence of skin barrier)
* Redistribution (hemodilution [as in Pregnancy], increased vascular permeability or decreased lymphatic clearance)
* Redistribution (hemodilution [as in [[pregnancy]]], increased vascular permeability or [[decreased]] lymphatic clearance)
* Acute disease states (referred to as a negative [[acute phase protein]])
* Acute disease states (referred to as a negative [[acute-phase protein]])
* [[Malnutrition]] and wasting<ref name="pmid22995885">{{cite journal | vauthors = Green P, Woglom AE, Genereux P, Daneault B, Paradis JM, Schnell S, Hawkey M, Maurer MS, Kirtane AJ, Kodali S, Moses JW, Leon MB, Smith CR, Williams M | title = The impact of frailty status on survival after transcatheter aortic valve replacement in older adults with severe aortic stenosis: a single-center experience | journal = [[Journal of the American College of Cardiology#Associated Journals.5B2.5D|JACC Cardiovascular Interventions]] | volume = 5 | issue = 9 | pages = 974–981 | year = 2012 | pmid = 22995885 | pmc = 3717525 | doi = 10.1016/j.jcin.2012.06.011 | url = http://www.sciencedirect.com/science/article/pii/S1936879812006310 | id =  }}</ref>
* Mutation causing analbuminemia (very rare)
* Mutation causing analbuminemia (very rare)


===Hyperalbuminemia===
===Hyperalbuminemia===
Typically is a sign of severe dehydration.
Hyperalbuminemia is an increased concentration of albumin in the blood.<ref name=Walker1990/> Typically, this condition is due to dehydration.<ref name=Walker1990>{{cite book|last1=Walker|first1=edited by H. Kenneth|last2=Hall|first2=W. Dallas|last3=Schlossberg|first3=J. Willis Hurst ; illustrations by Leon|last4=Boyter|first4=Charles H.|title=Clinical methods : the history, physical, and laboratory examinations|date=1990|publisher=Butterworths|location=Boston|isbn=040990077X|page=Chapter 101|edition=3rd|url=https://www.ncbi.nlm.nih.gov/books/NBK204/#_A3173_}}</ref>  Hyperalbuminemia has also been associated with high protein diets.<ref name="pmid16716979">{{cite journal | vauthors = Mutlu EA, Keshavarzian A, Mutlu GM | title = Hyperalbuminemia and elevated transaminases associated with high-protein diet | journal = Scand. J. Gastroenterol. | volume = 41 | issue = 6 | pages = 759–60 | date = June 2006 | pmid = 16716979 | doi = 10.1080/00365520500442625 }}</ref>
 
===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 Collaboration|Cochrane]] [[systematic review]]<ref>The Albumin Reviewers (Alderson P, Bunn F, Li Wan Po A, Li L, Pearson M, Roberts I, Schierhout G). [http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD001208.pub2/abstract Human albumin solution for resuscitation and volume expansion in critically ill patients]" ''Cochrane Database of Systematic Reviews'' 2004, Issue 4. Art. No.: CD001208. {{doi|10.1002/14651858.CD001208.pub2}}.</ref> 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 syndrome|frailty]] index.<ref name="pmid22995885" />


==Glycation (Glycosylation) of Serum Albumin ==
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 <ref>{{cite journal |author=Rajbar S |title=An abnormal hemoglobin in red cells of diabetics |journal=Clin Chim Acta |volume=22 |issue=2 |pages=296-8 |year=1968 |pmid=5687098}}</ref> and serum albumin <ref>{{cite journal |author=Day J, Thorpe S, Baynes J |title=Nonenzymatically glucosylated albumin. In vitro preparation and isolation from normal human serum |journal=J Biol Chem |volume=254 |issue=3 |pages=595-7 |year=1979 |pmid=762083}}</ref><ref>{{cite journal |author=Iberg N, Flückiger R |title=Nonenzymatic glycosylation of albumin in vivo. Identification of multiple glycosylated sites |journal=J Biol Chem |volume=261 |issue=29 |pages=13542-5 |year=1986 |pmid=3759977}}</ref> 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 (Millard reaction). This reaction can be inhibited in the presence of antioxidant agents <ref>{{cite journal |author=Jakus V, Hrnciarová M, Cársky J, Krahulec B, Rietbrock N |title=Inhibition of nonenzymatic protein glycation and lipid peroxidation by drugs with antioxidant activity |journal=Life Sci |volume=65 |issue=18-19 |pages=1991-3 |year=1999 |pmid=10576452}}</ref>. Although this reaction may happen normally <ref>{{cite journal |author=Day J, Thorpe S, Baynes J |title=Nonenzymatically glucosylated albumin. In vitro preparation and isolation from normal human serum |journal=J Biol Chem |volume=254 |issue=3 |pages=595-7 |year=1979 |pmid=762083}}</ref> , elevated glycoalbumin is observed in diabetes mellitus <ref>{{cite journal |author=Iberg N, Flückiger R |title=Nonenzymatic glycosylation of albumin in vivo. Identification of multiple glycosylated sites |journal=J Biol Chem |volume=261 |issue=29 |pages=13542-5 |year=1986 |pmid=3759977}}</ref>.


Glycation has the potential to alter the biological structure and function of the serum albumin protein <ref>{{cite journal |author=Mohamadi-Nejad A, Moosavi-Movahedi A, Hakimelahi G, Sheibani N |title=Thermodynamic analysis of human serum albumin interactions with glucose: insights into the diabetic range of glucose concentration |journal=Int J Biochem Cell Biol |volume=34 |issue=9 |pages=1115-24 |year=2002 |pmid=12009306}}</ref><ref>{{cite journal |author=Shaklai N, Garlick R, Bunn H |title=Nonenzymatic glycosylation of human serum albumin alters its conformation and function |journal=J Biol Chem |volume=259 |issue=6 |pages=3812-7 |year=1984 |pmid=6706980}}</ref><ref>{{cite journal |author=Mendez D, Jensen R, McElroy L, Pena J, Esquerra R |title=The effect of non-enzymatic glycation on the unfolding of human serum albumin |journal=Arch Biochem Biophys |volume=444 |issue=2 |pages=92-9 |year=2005 |pmid=16309624}}</ref><ref>{{cite journal |author=Mohamadi-Nejad A. et al.|title= The thermal analysisnext term of nonezymatic previous termglycosylation of human serum albumin:next term differential scanning calorimetry and circular dichroism studies |journal= Thermochimica Acta |volume=389 |issue=1-2 |pages=141-151 |year=2002 |doi=10.1016/S0040-6031(02)00006-0 }}</ref>. Moreover, the glycation finally 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 via 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 <ref>{{cite journal |author=Kańska U, Boratyński J |title=Thermal glycation of proteins by D-glucose and D-fructose |journal=Arch Immunol Ther Exp (Warsz) |volume=50 |issue=1 |pages=61-6 |year=2002 |pmid=11916310}}</ref>. They also interfere with the normal product of nitric oxide in cells <ref>{{cite journal |author=Rojas A, Romay S, González D, Herrera B, Delgado R, Otero K |title=Regulation of endothelial nitric oxide synthase expression by albumin-derived advanced glycosylation end products |journal=Circ Res |volume=86 |issue=3 |pages=E50-4 |year=2000 |pmid=10679490}}</ref>.
Human serum albumin may be used to potentially reverse drug/chemical toxicity by binding to free drug/agent. (Tatlow, D, Poothencheri, S, Bhangal, R and Tatlow C. Novel method for rapid reversal of drug toxicity: A case report. doi|10.1111/1440-1681.12358). Ascentzi, P, Leboffe, L, Toti, D, Polticelli, F, and Trezza, V. Fipronil recognition by the FA1 site of human serum albumin. doi|10.1002/jmr.2713.


Although there are several lysine and arginine residues in the serum albumin structure, very few of them can take part in the glycation reaction <ref>{{cite journal |author=Iberg N, Flückiger R |title=Nonenzymatic glycosylation of albumin in vivo. Identification of multiple glycosylated sites |journal=J Biol Chem |volume=261 |issue=29 |pages=13542-5 |year=1986 |pmid=3759977}}</ref><ref>{{cite journal |author=Garlick R, Mazer J |title=The principal site of nonenzymatic glycosylation of human serum albumin in vivo |journal=J Biol Chem |volume=258 |issue=10 |pages=6142-6 |year=1983 |pmid=6853480}}</ref>. It is not clear exactly why only these residues are glycated in serum albumin <ref>{{cite journal |author=Marashi S. A., Safarian S., Moosavi-Movahedi A.A. |title=Why major nonenzymatic glycation sites of human serum albumin are preferred to other residues? |journal=Med Hypotheses |volume=64 |issue=4 |pages=881 |year=2005 |pmid=15694713}}</ref>.
==Glycation==
It has been known for a long time that human blood proteins like hemoglobin<ref name="pmid5687098">{{cite journal | vauthors = Rahbar S | title = An abnormal hemoglobin in red cells of diabetics | journal = Clin. Chim. Acta | volume = 22 | issue = 2 | pages = 296–8 | date = October 1968 | pmid = 5687098 | doi = 10.1016/0009-8981(68)90372-0 }}</ref>  and serum albumin<ref name="nonenzymatically595">{{cite journal | vauthors = Day JF, Thorpe SR, Baynes JW | title = Nonenzymatically glucosylated albumin. In vitro preparation and isolation from normal human serum | journal = J. Biol. Chem. | volume = 254 | issue = 3 | pages = 595–7 | date = February 1979 | pmid = 762083 | doi =  }}</ref><ref name="identification13542">{{cite journal | vauthors = Iberg N, Flückiger R | title = Nonenzymatic glycosylation of albumin in vivo. Identification of multiple glycosylated sites | journal = J. Biol. Chem. | volume = 261 | issue = 29 | pages = 13542–5 | date = October 1986 | pmid = 3759977 | doi =  }}</ref> 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.<ref name="pmid10576452">{{cite journal | vauthors = Jakus V, Hrnciarová M, Cársky J, Krahulec B, Rietbrock N | title = Inhibition of nonenzymatic protein glycation and lipid peroxidation by drugs with antioxidant activity | journal = Life Sci. | volume = 65 | issue = 18–19 | pages = 1991–3 | year = 1999 | pmid = 10576452 | doi = 10.1016/S0024-3205(99)00462-2 }}</ref> Although this reaction may happen normally,<ref name="nonenzymatically595"/> elevated glycoalbumin is observed in diabetes mellitus.<ref name="identification13542"/>


==Testing for albumin loss via the kidneys==
Glycation has the potential to alter the biological structure and function of the serum albumin protein.<ref name="pmid12009306">{{cite journal | vauthors = Mohamadi-Nejad A, Moosavi-Movahedi AA, Hakimelahi GH, Sheibani N | title = Thermodynamic analysis of human serum albumin interactions with glucose: insights into the diabetic range of glucose concentration | journal = Int. J. Biochem. Cell Biol. | volume = 34 | issue = 9 | pages = 1115–24 | date = September 2002 | pmid = 12009306 | doi = 10.1016/S1357-2725(02)00031-6 }}</ref><ref name="pmid6706980">{{cite journal | vauthors = Shaklai N, Garlick RL, Bunn HF | title = Nonenzymatic glycosylation of human serum albumin alters its conformation and function | journal = J. Biol. Chem. | volume = 259 | issue = 6 | pages = 3812–7 | date = March 1984 | pmid = 6706980 | doi = }}</ref><ref name="pmid16309624">{{cite journal | vauthors = Mendez DL, Jensen RA, McElroy LA, Pena JM, Esquerra RM | title = The effect of non-enzymatic glycation on the unfolding of human serum albumin | journal = Arch. Biochem. Biophys. | volume = 444 | issue = 2 | pages = 92–9 | date = December 2005 | pmid = 16309624 | doi = 10.1016/j.abb.2005.10.019 }}</ref><ref name="Mohamadi-Nejada_2002">{{cite journal | last = Mohamadi-Nejada A, Moosavi-Movahedi AA, Safariana S, Naderi-Maneshc MH, Ranjbarc B, Farzamid B, Mostafavie H, Larijanif MB, Hakimelahi GH | title = The thermal analysis of nonezymatic glycosylation of human serum albumin: differential scanning calorimetry and circular dichroism studies | journal = Thermochimica Acta |date=July 2002 | volume = 389 | issue = 1–2 | pages = 141–151 | doi = 10.1016/S0040-6031(02)00006-0 | first1 = A}}</ref>
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 [[kidney diseases|diseases]] including [[diabetic nephropathy]], a major complication of uncontrolled [[diabetes]] where proteins can cross the glomerulus. The lost albumin can be detected by a simple urine test [http://www.webmd.com/hw/diabetes_1_2/tu6440.asp].  Depending on the amount of albumin lost, a patient may have normal renal function, [[microalbuminuria]], or [[albuminuria]].


==Amino Acid Sequence==
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.<ref name="pmid11916310">{{cite journal | vauthors = Kańska U, Boratyński J | title = Thermal glycation of proteins by D-glucose and D-fructose | journal = Arch. Immunol. Ther. Exp. (Warsz.) | volume = 50 | issue = 1 | pages = 61–6 | year = 2002 | pmid = 11916310 | doi =  }}</ref> They also interfere with the normal product of nitric oxide in cells.<ref name="pmid10679490">{{cite journal | vauthors = Rojas A, Romay S, González D, Herrera B, Delgado R, Otero K | title = Regulation of endothelial nitric oxide synthase expression by albumin-derived advanced glycosylation end products | journal = Circ. Res. | volume = 86 | issue = 3 | pages = E50–4 | date = February 2000 | pmid = 10679490 | doi = 10.1161/01.RES.86.3.e50 }}</ref>
The approximate sequence of human serum albumin is:
 
Although there are several lysine and arginine residues in the serum albumin structure, very few of them can take part in the glycation reaction.<ref name="identification13542"/><ref name="pmid6853480">{{cite journal | vauthors = Garlick RL, Mazer JS | title = The principal site of nonenzymatic glycosylation of human serum albumin in vivo | journal = J. Biol. Chem. | volume = 258 | issue = 10 | pages = 6142–6 | date = May 1983 | pmid = 6853480 | doi =  }}</ref> 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.<ref name="pmid15694713">{{cite journal | vauthors = Marashi SA, Safarian S, Moosavi-Movahedi AA | title = Why major nonenzymatic glycation sites of human serum albumin are preferred to other residues? | journal = Med. Hypotheses | volume = 64 | issue = 4 | pages = 881 | year = 2005 | pmid = 15694713 | doi = 10.1016/j.mehy.2004.11.007 }}</ref>
 
==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.<ref>Kawakami A, Kubota K, Yamada N, Tagami U, Takehana T, Sonaka I, Suzuki I, Hirayama K (2006). Identification and characterization of oxidized human serum albumin. FEBS J, 273:3346–3357. Doi: 10.1111/j.1742-4658.2006.05341.x</ref> 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).<ref>Turell L, Carballal L, Botti H, Radi R, Alvarez B. (2009). Oxidation of the albumin thiol to sulfenic acid and its implications in the intravascular compartment. Braz J Med Biol Res 42:305–311.</ref> However, in pathological states characterized by oxidative stress and during the aging process, the oxidized form, or non-mercaptoalbumin (HNA), could predominate.<ref>Rosas-Díaz M, Camarillo-Cadena M, Hernández-Arana A, Ramón-Gallegos E, Medina-Navarro R. (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, 404:193–201.</ref> The albumin thiol reacts with radical hydroxyl (.OH), hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) 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.<ref>Matsuyama Y, Terawaki H, Terada T, Era S. (2011). Albumin thiol oxidation and serum protein carbonyl formation are progressively enhanced with advancing stages of chronic kidney disease. Clin Exp Nephrol, 13(4):308–315.</ref>  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 [[kidney diseases|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.<ref>[http://www.webmd.com/hw/diabetes_1_2/tu6440.asp Microalbumin Urine Test<!-- Bot generated title -->]</ref> 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:<ref>{{UniProt Full|P02768|Serum albumin}}</ref>


<tt>''MKWVTFISLL FLFSSAYSRG VFRR''DAHKSE 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</tt>
<tt>''MKWVTFISLL FLFSSAYSRG VFRR''DAHKSE 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</tt>


Where 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.
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]] (1–18) and [[propeptide]] (19–22, or 19–24{{citation needed|date=June 2015}}) portions, are cleaved [[post-translational modification|after translation]].
 
==Interactions==
Human serum albumin has been shown to [[Protein-protein interaction|interact]] with [[FCGRT]].<ref name="pmid12566415">{{cite journal | vauthors = Chaudhury C, Mehnaz S, Robinson JM, Hayton WL, Pearl DK, Roopenian DC, Anderson CL | title = The Major Histocompatibility Complex–related Fc Receptor for IgG (FcRn) Binds Albumin and Prolongs Its Lifespan | journal = J. Exp. Med. | volume = 197 | issue = 3 | pages = 315–22 | date = February 2003 | pmid = 12566415 | pmc = 2193842 | doi = 10.1084/jem.20021829 }}</ref>


==See also==
==See also==
* [[Reference ranges for common blood tests]]
* [[Bovine serum albumin]]
* [[Bovine serum albumin]]
* [[Serum albumin]]


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


==Further reading==
== Further reading ==
{{refbegin | 2}}
{{Refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Komatsu T, Nakagawa A, Curry S, Tsuchida E, Murata K, Nakamura N, Ohno H | title = 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 | journal = Org. Biomol. Chem. | volume = 7 | issue = 18 | pages = 3836–41 | year = 2009 | pmid = 19707690 | doi = 10.1039/b909794e }}
| citations =  
* {{cite journal | vauthors = Milojevic J, Raditsis A, Melacini G | title = Human Serum Albumin Inhibits Aβ Fibrillization through a "Monomer-Competitor" Mechanism | journal = Biophys. J. | volume = 97 | issue = 9 | pages = 2585–94 | year = 2009 | pmid = 19883602 | pmc = 2770600 | doi = 10.1016/j.bpj.2009.08.028 }}
*{{cite journal  | author=Curry S |title=Beyond expansion: structural studies on the transport roles of human serum albumin. |journal=Vox Sang. |volume=83 Suppl 1 |issue=  |pages= 315-9 |year= 2003 |pmid= 12617161 |doi= }}
* {{cite journal | vauthors = Silva AM, Hider RC | title = Influence of non-enzymatic post-translation modifications on the ability of human serum albumin to bind iron. Implications for non-transferrin-bound iron speciation | journal = Biochim. Biophys. Acta | volume = 1794 | issue = 10 | pages = 1449–58 | year = 2009 | pmid = 19505594 | doi = 10.1016/j.bbapap.2009.06.003 }}
}}
* {{cite journal | vauthors = Otosu T, Nishimoto E, Yamashita S | title = Multiple conformational state of human serum albumin around single tryptophan residue at various pH revealed by time-resolved fluorescence spectroscopy | journal = J. Biochem. | volume = 147 | issue = 2 | pages = 191–200 | year = 2010 | pmid = 19884191 | doi = 10.1093/jb/mvp175 }}
{{refend}}
* {{cite journal | vauthors = Blindauer CA, Harvey I, Bunyan KE, Stewart AJ, Sleep D, Harrison DJ, Berezenko S, Sadler PJ | title = Structure, Properties, and Engineering of the Major Zinc Binding Site on Human Albumin | journal = J. Biol. Chem. | volume = 284 | issue = 34 | pages = 23116–24 | year = 2009 | pmid = 19520864 | pmc = 2755717 | doi = 10.1074/jbc.M109.003459 }}
* {{cite journal | vauthors = Juárez J, López SG, Cambón A, Taboada P, Mosquera V | title = Influence of electrostatic interactions on the fibrillation process of human serum albumin | journal = J Phys Chem B | volume = 113 | issue = 30 | pages = 10521–9 | year = 2009 | pmid = 19572666 | doi = 10.1021/jp902224d }}
* {{cite journal | vauthors = Fu BL, Guo ZJ, Tian JW, Liu ZQ, Cao W | title = [Advanced glycation end products induce expression of PAI-1 in cultured human proximal tubular epithelial cells through NADPH oxidase dependent pathway] | journal = Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi | volume = 25 | issue = 8 | pages = 674–7 | year = 2009 | pmid = 19664386 | doi = }}
* {{cite journal | vauthors = Ascenzi P, di Masi A, Coletta M, Ciaccio C, Fanali G, Nicoletti FP, Smulevich G, Fasano M | title = Ibuprofen Impairs Allosterically Peroxynitrite Isomerization by Ferric Human Serum Heme-Albumin | journal = J. Biol. Chem. | volume = 284 | issue = 45 | pages = 31006–17 | year = 2009 | pmid = 19734142 | pmc = 2781501 | doi = 10.1074/jbc.M109.010736 }}
* {{cite journal | vauthors = Sowa ME, Bennett EJ, Gygi SP, Harper JW | title = Defining the Human Deubiquitinating Enzyme Interaction Landscape | journal = Cell | volume = 138 | issue = 2 | pages = 389–403 | year = 2009 | pmid = 19615732 | pmc = 2716422 | doi = 10.1016/j.cell.2009.04.042 }}
* {{cite journal | vauthors = Curry S | title = Beyond expansion: structural studies on the transport roles of human serum albumin | journal = Vox Sang. | volume = 83 Suppl 1 | issue =  | pages = 315–9 | year = 2002 | pmid = 12617161 | doi = 10.1111/j.1423-0410.2002.tb05326.x }}
* {{cite journal | vauthors = Guo S, Shi X, Yang F, Chen L, Meehan EJ, Bian C, Huang M | title = Structural basis of transport of lysophospholipids by human serum albumin | journal = Biochem. J. | volume = 423 | issue = 1 | pages = 23–30 | year = 2009 | pmid = 19601929 | doi = 10.1042/BJ20090913 }}
* {{cite journal | vauthors = de Jong PE, Gansevoort RT | title = Focus on microalbuminuria to improve cardiac and renal protection | journal = Nephron Clin Pract | volume = 111 | issue = 3 | pages = c204–10; discussion c211 | year = 2009 | pmid = 19212124 | doi = 10.1159/000201568 }}
* {{cite journal | vauthors = Page TA, Kraut ND, Page PM, Baker GA, Bright FV | title = Dynamics of loop 1 of domain I in human serum albumin when dissolved in ionic liquids | journal = J Phys Chem B | volume = 113 | issue = 38 | pages = 12825–30 | year = 2009 | pmid = 19711930 | doi = 10.1021/jp904475v }}
* {{cite journal | vauthors = Roche M, Rondeau P, Singh NR, Tarnus E, Bourdon E | title = The antioxidant properties of serum albumin | journal = FEBS Lett. | volume = 582 | issue = 13 | pages = 1783–7 | year = 2008 | pmid = 18474236 | doi = 10.1016/j.febslet.2008.04.057 }}
* {{cite journal | vauthors = Wyatt AR, Wilson MR | title = Identification of Human Plasma Proteins as Major Clients for the Extracellular Chaperone Clusterin | journal = J. Biol. Chem. | volume = 285 | issue = 6 | pages = 3532–9 | year = 2010 | pmid = 19996109 | pmc = 2823492 | doi = 10.1074/jbc.M109.079566 }}
* {{cite journal | vauthors = Cui FL, Yan YH, Zhang QZ, Qu GR, Du J, Yao XJ | title = A study on the interaction between 5-Methyluridine and human serum albumin using fluorescence quenching method and molecular modeling | journal = J Mol Model | volume = 16 | issue = 2 | pages = 255–62 | year = 2010 | pmid = 19588173 | doi = 10.1007/s00894-009-0548-4 }}
* {{cite journal | vauthors = Caridi G, Dagnino M, Simundic AM, Miler M, Stancic V, Campagnoli M, Galliano M, Minchiotti L | title = Albumin Benkovac (c.1175 A > G; p.Glu392Gly): a novel genetic variant of human serum albumin | journal = [[Translational Research (journal)|Translational Research]] | volume = 155 | issue = 3 | pages = 118–9 | year = 2010 | pmid = 20171595 | doi = 10.1016/j.trsl.2009.10.001 }}
* {{cite journal | vauthors = Deeb O, Rosales-Hernández MC, Gómez-Castro C, Garduño-Juárez R, Correa-Basurto J | title = Exploration of human serum albumin binding sites by docking and molecular dynamics flexible ligand-protein interactions | journal = Biopolymers | volume = 93 | issue = 2 | pages = 161–70 | year = 2010 | pmid = 19785033 | doi = 10.1002/bip.21314 }}
* {{cite journal | vauthors = Karahan SC, Koramaz I, Altun G, Uçar U, Topbaş M, Menteşe A, Kopuz M | title = 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 | journal = Eur Surg Res | volume = 44 | issue = 1 | pages = 30–6 | year = 2010 | pmid = 19955769 | doi = 10.1159/000262324 }}
* {{cite journal | vauthors = Jin C, Lu L, Zhang RY, Zhang Q, Ding FH, Chen QJ, Shen WF | title = Association of serum glycated albumin, C-reactive protein and ICAM-1 levels with diffuse coronary artery disease in patients with type 2 diabetes mellitus | journal = Clin. Chim. Acta | volume = 408 | issue = 1–2 | pages = 45–9 | year = 2009 | pmid = 19615354 | doi = 10.1016/j.cca.2009.07.003 }}
{{Refend}}


==External links==
== External links ==
* [http://160.114.99.91/astrojan/protein/pictures/albumin3.jpg Human Albumin structure] in the [[Protein data bank]] [http://www.rcsb.org/pdb/cgi/explore.cgi?pid=52421101802426&page=0&pdbId=1AO6]
* [http://160.114.99.91/astrojan/protein/pictures/albumin3.jpg Human Albumin structure] in the [[Protein data bank]]
* [http://us.expasy.org/uniprot/P02768 Human Albumin information in the Swis-Prot/TrEMBL database]
* [http://us.expasy.org/uniprot/P02768 Human Albumin information in the Swis-Prot/TrEMBL database]
* [http://www.hprd.org/summary?protein=00062&isoform_id=00062_1&isoform_name=Isoform_1 Human Serum Albumin] on the [http://www.hprd.org/ Human Protein Reference Database]
* [http://www.hprd.org/summary?protein=00062&isoform_id=00062_1&isoform_name=Isoform_1 Human Serum Albumin] on the [http://www.hprd.org/ Human Protein Reference Database]
* [http://albumin.althotas.com/ Albumin binding prediction]
* Albumin at [http://labtestsonline.org/understanding/analytes/albumin/tab/test Lab Tests Online]
* [http://www.acb.org.uk/Nat%20Lab%20Med%20Hbk/Albumin.pdf Albumin: analyte monograph] from the Association for Clinical Biochemistry and Laboratory Medicine


{{PDB Gallery|geneid=213}}
{{Albumins}}
{{Albumins}}
{{Acute phase proteins}}  
{{Acute phase proteins}}
[[Category:Proteins]]
{{Nuclear receptor modulators}}
 
{{DEFAULTSORT:Human Serum Albumin}}
[[Category:Blood proteins]]
[[Category:Blood proteins]]
 
[[Category:Liver function tests]]
[[de:Humanalbumin]]
{{WikiDoc Sources}}

Latest revision as of 11:52, 10 January 2019

human serum albumin
File:1e7h.jpg
PDB rendering based on 1e7h.
Identifiers
SymbolALB
Entrez213
HUGO399
OMIM103600
PDB1E7H
RefSeqNM_000477
UniProtP02768
Other data
LocusChr. 4 q13.3

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 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).[1] 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 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.

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.[2]

Reference ranges

Serum albumin concentration is typically 35–50 g/L (3.5–5.0 g/dL).[1]

Pathology

Hypoalbuminemia

Hypoalbuminemia means low blood albumin levels.[3] This can be caused by:

Hyperalbuminemia

Hyperalbuminemia is an increased concentration of albumin in the blood.[5] Typically, this condition is due to dehydration.[5] Hyperalbuminemia has also been associated with high protein diets.[6]

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[7] 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.[4]

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.

Human serum albumin may be used to potentially reverse drug/chemical toxicity by binding to free drug/agent. (Tatlow, D, Poothencheri, S, Bhangal, R and Tatlow C. Novel method for rapid reversal of drug toxicity: A case report. doi|10.1111/1440-1681.12358). Ascentzi, P, Leboffe, L, Toti, D, Polticelli, F, and Trezza, V. Fipronil recognition by the FA1 site of human serum albumin. doi|10.1002/jmr.2713.

Glycation

It has been known for a long time that human blood proteins like hemoglobin[8] and serum albumin[9][10] 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.[11] Although this reaction may happen normally,[9] elevated glycoalbumin is observed in diabetes mellitus.[10]

Glycation has the potential to alter the biological structure and function of the serum albumin protein.[12][13][14][15]

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.[16] They also interfere with the normal product of nitric oxide in cells.[17]

Although there are several lysine and arginine residues in the serum albumin structure, very few of them can take part in the glycation reaction.[10][18] 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.[19]

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.[20] 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).[21] However, in pathological states characterized by oxidative stress and during the aging process, the oxidized form, or non-mercaptoalbumin (HNA), could predominate.[22] 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.[23] 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.[24] 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:[25]

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 (1–18) and propeptide (19–22, or 19–24[citation needed]) portions, are cleaved after translation.

Interactions

Human serum albumin has been shown to interact with FCGRT.[26]

See also

References

  1. ↑ 1.0 1.1 "Harmonisation of Reference Intervals" (PDF). pathologyharmony.co.uk. Pathology Harmony. Retrieved 23 June 2013.
  2. ↑ "Albumin: analyte monograph" (PDF). Association for Clinical Biochemistry and Laboratory Medicine. Archived from the original (PDF) on 13 November 2012. Retrieved 23 June 2013.
  3. ↑ Anderson, Douglas M. (2000). Dorland's illustrated medical dictionary (29. ed.). Philadelphia [u.a.]: Saunders. p. 860. ISBN 0721682618.
  4. ↑ 4.0 4.1 Green P, Woglom AE, Genereux P, Daneault B, Paradis JM, Schnell S, Hawkey M, Maurer MS, Kirtane AJ, Kodali S, Moses JW, Leon MB, Smith CR, Williams M (2012). "The impact of frailty status on survival after transcatheter aortic valve replacement in older adults with severe aortic stenosis: a single-center experience". JACC Cardiovascular Interventions. 5 (9): 974–981. doi:10.1016/j.jcin.2012.06.011. PMC 3717525. PMID 22995885.
  5. ↑ 5.0 5.1 Walker, edited by H. Kenneth; Hall, W. Dallas; Schlossberg, J. Willis Hurst ; illustrations by Leon; Boyter, Charles H. (1990). Clinical methods : the history, physical, and laboratory examinations (3rd ed.). Boston: Butterworths. p. Chapter 101. ISBN 040990077X.
  6. ↑ Mutlu EA, Keshavarzian A, Mutlu GM (June 2006). "Hyperalbuminemia and elevated transaminases associated with high-protein diet". Scand. J. Gastroenterol. 41 (6): 759–60. doi:10.1080/00365520500442625. PMID 16716979.
  7. ↑ The Albumin Reviewers (Alderson P, Bunn F, Li Wan Po A, Li L, Pearson M, Roberts I, Schierhout G). Human albumin solution for resuscitation and volume expansion in critically ill patients" Cochrane Database of Systematic Reviews 2004, Issue 4. Art. No.: CD001208. doi:10.1002/14651858.CD001208.pub2.
  8. ↑ Rahbar S (October 1968). "An abnormal hemoglobin in red cells of diabetics". Clin. Chim. Acta. 22 (2): 296–8. doi:10.1016/0009-8981(68)90372-0. PMID 5687098.
  9. ↑ 9.0 9.1 Day JF, Thorpe SR, Baynes JW (February 1979). "Nonenzymatically glucosylated albumin. In vitro preparation and isolation from normal human serum". J. Biol. Chem. 254 (3): 595–7. PMID 762083.
  10. ↑ 10.0 10.1 10.2 Iberg N, Flückiger R (October 1986). "Nonenzymatic glycosylation of albumin in vivo. Identification of multiple glycosylated sites". J. Biol. Chem. 261 (29): 13542–5. PMID 3759977.
  11. ↑ 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 Sci. 65 (18–19): 1991–3. doi:10.1016/S0024-3205(99)00462-2. PMID 10576452.
  12. ↑ 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". Int. J. Biochem. Cell Biol. 34 (9): 1115–24. doi:10.1016/S1357-2725(02)00031-6. PMID 12009306.
  13. ↑ Shaklai N, Garlick RL, Bunn HF (March 1984). "Nonenzymatic glycosylation of human serum albumin alters its conformation and function". J. Biol. Chem. 259 (6): 3812–7. PMID 6706980.
  14. ↑ 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". Arch. Biochem. Biophys. 444 (2): 92–9. doi:10.1016/j.abb.2005.10.019. PMID 16309624.
  15. ↑ Mohamadi-Nejada A, Moosavi-Movahedi AA, Safariana S, Naderi-Maneshc MH, Ranjbarc B, Farzamid B, Mostafavie H, Larijanif MB, Hakimelahi GH, A (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.
  16. ↑ Kańska U, Boratyński J (2002). "Thermal glycation of proteins by D-glucose and D-fructose". Arch. Immunol. Ther. Exp. (Warsz.). 50 (1): 61–6. PMID 11916310.
  17. ↑ 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". Circ. Res. 86 (3): E50–4. doi:10.1161/01.RES.86.3.e50. PMID 10679490.
  18. ↑ Garlick RL, Mazer JS (May 1983). "The principal site of nonenzymatic glycosylation of human serum albumin in vivo". J. Biol. Chem. 258 (10): 6142–6. PMID 6853480.
  19. ↑ Marashi SA, Safarian S, Moosavi-Movahedi AA (2005). "Why major nonenzymatic glycation sites of human serum albumin are preferred to other residues?". Med. Hypotheses. 64 (4): 881. doi:10.1016/j.mehy.2004.11.007. PMID 15694713.
  20. ↑ Kawakami A, Kubota K, Yamada N, Tagami U, Takehana T, Sonaka I, Suzuki I, Hirayama K (2006). Identification and characterization of oxidized human serum albumin. FEBS J, 273:3346–3357. Doi: 10.1111/j.1742-4658.2006.05341.x
  21. ↑ Turell L, Carballal L, Botti H, Radi R, Alvarez B. (2009). Oxidation of the albumin thiol to sulfenic acid and its implications in the intravascular compartment. Braz J Med Biol Res 42:305–311.
  22. ↑ Rosas-Díaz M, Camarillo-Cadena M, Hernández-Arana A, Ramón-Gallegos E, Medina-Navarro R. (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, 404:193–201.
  23. ↑ Matsuyama Y, Terawaki H, Terada T, Era S. (2011). Albumin thiol oxidation and serum protein carbonyl formation are progressively enhanced with advancing stages of chronic kidney disease. Clin Exp Nephrol, 13(4):308–315.
  24. ↑ Microalbumin Urine Test
  25. ↑ Universal protein resource accession number P02768 for "Serum albumin" at UniProt.
  26. ↑ Chaudhury C, Mehnaz S, Robinson JM, Hayton WL, Pearl DK, Roopenian DC, Anderson CL (February 2003). "The Major Histocompatibility Complex–related Fc Receptor for IgG (FcRn) Binds Albumin and Prolongs Its Lifespan". J. Exp. Med. 197 (3): 315–22. doi:10.1084/jem.20021829. PMC 2193842. PMID 12566415.

Further reading

External links

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